An orthogonal frequency division multiplexing (OFDM) demodulating apparatus includes a delay profile creating section, a Fourier converting section, a pilot signal extracting section, a transmission path characteristic estimating section, an inverse Fourier converting section, and a window control section. In this case, the window control section creates a delay profile for defining a calculation range by leaving a path which exists at a same position in both the delay profiles created by the delay profile creating section and the inverse Fourier converting section and the number of times of detection which is equal to or higher than a threshold value and defines a higher threshold value for the path at a predetermined position from the position of the main path within the delay profile created by the inverse Fourier converting section than for the paths at the other positions.

1. Field of the Invention
The present invention relates to an orthogonal frequency division multiplexing (OFDM) demodulating apparatus and method thereof that demodulates an OFDM signal.
2. Description of the Related Art
In recent years, a modulating method called Orthogonal Frequency Division Multiplexing method (called OFDM method hereinafter) has been proposed for modulating digital data. In OFDM method, data is assigned and is digitally modulated to the amplitude and phase of each of many orthogonal sub-carriers within a transmission band by PSK (Phase Shift Keying) or a QAM (Quadrature Amplitude Modulation).
OFDM method has been widely considered to apply to terrestrial digital broadcasting, which is susceptible to multipath interference.
A send signal by OFDM method is transmitted in symbols called OFDM symbols as shown in FIG. 14. The OFDM symbol includes a valid symbol and a guard interval. The valid symbol is a signal period when IFFT (Inverse Fast Fourier Transform) is performed upon transmission. The guard interval is a copy of the waveform of a part of the second half of the valid symbol. The guard inertial is provided in the first half of the OFDM symbol and may have a time length of ¼ or ⅛ of that of the valid symbol, for example.
In an OFDM receiving apparatus that receives the OFDM signal, FFT (Fast Fourier Transform) calculation is performed thereon by an FFT calculating circuit, whereby the received OFDM signal is demodulated. From the OFDM symbol including a valid symbol and a guard interval, the OFDM receiving apparatus detects the boundary position of the OFDM symbol, defines a calculation range (called FFT window) of a length equal to that of the valid symbol from the detected symbol boundary position, identifies the data of the part defined by the FFT window from the OFDM symbol and performs FFT calculation thereon.
By the way, terrestrial broadcasting is a transmission path in a multipath atmosphere. In other words, terrestrial broadcasting is susceptible to the interference by delay waves due to the surroundings such as the surrounding geography and buildings at the receiving point, and the signal received by an OFDM receiving apparatus becomes a composite wave resulting from the combination of multiple delay waves.
In the transmission path in a multipath atmosphere, multiple symbol boundaries exist because of the existence of multiple paths. In this case, the inter-symbol interference may be generally avoided by defining the position of an FFT window based on the position of the symbol boundary of the first reached path.
Here, a method of defining the position of an FFT window, which determines the position of FFT calculation, will be described (see JP-A-2002-368717 and JP-A-2001-292125).
A first method of defining an FFT window delays an OFDM signal before FFT calculation is performed thereon, obtains the correlation between the waveform of the guard interval part and the waveform of the second half of the OFDM symbol (that is, the signal waveform from which the guard interval is copied), and calculates the boundary of the OFDM symbol. In this method, the time exhibiting the peak value of the autocorrelation function is the boundary of the OFDM symbol of each path.
A second method applies scattered pilot signals (SP signals) with a specific level and specific phase, which are scattered at specific positions in an OFDM symbol. The method estimates the transmission path characteristic of all OFDM symbols by extracting the SP signal from an OFDM signal, removing the modulated component therefrom and performing interpolation thereon by using a time direction interpolation filter. Then, a delay profile exhibiting the signal strength of each path is created by performing IFFT calculation on the estimated transmission path characteristic, and the boundary of the OFDM symbol is obtained based on the first reached path. Notably, the time direction interpolation of SP signals is for increasing the range of the detection of a delay profile by decreasing the intervals of SP signals artificially.
In general, in defining an FFT window, the first method causes a rough trigger to an FFT window at the beginning of receipt, and, after a predetermined period of time of the continuation of the first method, the second method causes the trigger to an FFT window. In other words, the establishment of rough synchronization is followed by more accurate symbol synchronization, resulting in a stable reproduction state.
A third method of defining an FFT window is also known that extracts the waveform of a guard interval part from an OFDM signal before FFT calculation is performed thereon, obtains the coherence between the extracted waveform and the waveform of the second half of the OFDM symbol and thereby obtains the boundary of the OFDM symbol. This method creates a delay profile exhibiting the signal strength of each path by obtaining the coherence and obtains the boundary of the OFDM symbol based on the first reached path.
Furthermore, in recent years, a method including a combination of the second and third methods has been proposed (see JP-A-2004-153831). The method allows the elimination of a false path by combining the delay profiles created by the two methods even when a false path due to noise exists in the delay profiles.
The second method may require the agreement between the interpolation value and the real transmission path characteristic since the SP signals are interpolated in the time direction. However, in an atmosphere in motion, the transmission path characteristic fluctuates at a high Doppler frequency, and a wrong delay profile might be created when the time-direction interpolation processing does not satisfy the sampling theorem.
FIGS. 15A and 15B show examples of cases in which the time-dependent fluctuation of a transmission path characteristic satisfies and does not satisfy a sampling theorem, respectively. As shown in FIG. 15A, when the time-dependent fluctuation of a transmission path characteristic satisfies the sampling theorem, the interpolation values (indicated by circles in white) of the SP signals (indicated by circles in black) agree with the real transmission path characteristic. On the other hand, as shown in FIG. 15B, when the time-dependent fluctuation of the transmission path does not satisfy the sampling theorem, the interpolation value (circles in white) of the SP signals (circles in black) do not agree with the real transmission path characteristic, resulting in the wrong estimation of the transmission path characteristic as indicated by the shown broken line.
FIG. 16 shows a delay profile resulting from the IFFT calculation performed when the time-dependent fluctuation of the transmission path characteristic does not satisfy the sampling theorem. As shown in FIG. 16, when the time-dependent fluctuation of the transmission path characteristic does not satisfy the sampling theorem, some time-direction interpolation may cause a pseudo path, which does not really exist, in addition to the real path that really exists. The pseudo path occurs regularly at the position of a normalized frequency of π/2, π or 3π/2 from the position of the real path.
Since a delay profile includes a pseudo path when time-direction interpolation is performed on SP signals, the definition of an FFT window may require the determination of either real path or pseudo path in order not to obtain the boundary of an OFDM symbol based on a pseudo path.
While a false path due to noise occurs at a random position, the pseudo path continuously occurs at a same position. Thus, when the position of the pseudo path in the delay profile created by the second method agrees with the position of the false path in the delay profile created by the third method, the pseudo path may be misdetermined as a real path even though the delay profiles of both are applied. As a result, the precision of the estimation of the delay profiles decreases.
Furthermore, in an atmosphere in motion, the precision of the estimation of delay profiles also decreases when the SNR (Signal to Noise Ratio) is deteriorated by a factor such as a fall of signal power.


A computer-implemented method for processing data used by a business application consistent with the present invention may include receiving electronic form data comprising layout data and representations of interactive elements, combining the electronic form data with customer specific data from a database to generate an intermediate form document in a data format capable of being output to a printer as a blank form without further modification, and converting the intermediate form document into a third document in a data format for display to a customer by a browser. The third document displayed to the customer looks the same as the blank form, receiving customer input data received from a customer via the third document, and associating the customer input data with the customer specific data in the business application.

In a traditional meaning, a "form" is a printed or typed document with blank spaces for insertion of required or requested information. A form is convenient for communication, for example, from an organization to a customer. Taking an invoice document as an illustrative example, the document is a filled-in form. The form contains a standardized portion for defining name and date fields (i.e. the "form") and a specialized portion for the particular name and particular date. With the advent of computer technology and the use of computer applications either by the organization or by the person, electronic forms have become widespread.
Organizations use business application programs to organize information flow within the organization or to communicate to and from the organization. Application programs are, for example, programs to assist customer relationship management (CRM), finance management, and human resource management. Although application programs differ from one another and are often customized to the organization, it is common for most of them that information leaving the organization in a final document is on a traditional medium, such as paper.
Often, the documents on paper are invoices, delivery notes, reminder letters, purchase orders, checks, or customs declarations. For example, an invoice has pages (e.g., sheets of paper), text areas (e.g., for printing positions to be invoiced, often in tables; greetings to the recipient), an address area (e.g., for printing recipients' address), and a graphic area (e.g., for printing a logotype of the sender).
Layout definitions comprise, for example, page breaks, line breaks, fonts indicators, position information, indent, tabulators, protection against line breaks in paragraph, and others.
Designing forms no longer require the designer to be computer-language literate. He or she benefits from builder software with a graphical interface such as, for example, the "Smart Forms" software, commercially available from SAP AG, Walldorf (Baden), Germany.
At a first time point, the designer creates a new form by a so-called "form builder", a computer program that resembles a commercially-available text and image processing program.
At a second, later time point, an output program reads data from the application program, instantiates the form, and prints the documents or generates an XML-output for displaying the document by a web browser. The output program receives the data via a predefined form-interface from the application program.
So far, using forms and documents as described above technically only allows unidirectional communication. In other words, the document (and the information embodied thereon) goes from the organization to the customer. However, communication in the opposite direction is often desired as well. There is an ongoing need to provide form-defining software that allows forms with bi-directional communication capacity.

Methods and systems for providing a document with interactive elements to retrieve information for processing by business applications


This invention is to provide a nanodevice, which is combined with an electronic device such as a diode, tunnel device and MOS transistor, integrated circuit and manufacturing method of the nanodevice. A nanodevice includes: a first insulating layer 2; one electrode 5A and the other electrode 5B provided to have a nanogap on the first insulating layer 2; a metal nanoparticle or a functional molecule provided between the one electrode 5A and the other electrode 5B; a second insulating layer 8 provided on the first insulating layer 2, and on the one electrode 5A and the other electrode 5B to embed the metal nanoparticle or the functional molecule. The second insulating layer works as a passivating layer.

Single electron transistor is one of nanodevices. To establish manufacturing technology for the single electron transistor, focusing on a gold nanoparticle as Coulomb island in single-electron device, the inventors used STM and clarified that the gold nanoparticle with particle diameter of 1.8 nm functioned as Coulomb island at ambient temperature. In addition, aiming to construct an electronic device on solid substrate, the inventors used electroless plating and established the method for manufacturing nanogap electrodes with a gap separation of 5 nm at a high yield rate at a time. Furthermore, the inventors reported on function of the single electron transistor, in which the gold nanoparticle was placed between the nanogap electrodes by chemical adsorption (Non-Patent Literatures 1 to 5).

Nanodevice and method for fabricating the same


A system for forming apertures in a flexible film is provided. The system includes a punching tool for forming apertures in a flexible film. The punching tool defines a through hole therethrough. The system also includes a support plate. The punching tool is configured to press the flexible film against the support plate to form the apertures.

Flexible films are often used in packaging, for example, in the food packaging industry (e.g., fruit packaging, vegetable packaging, etc.). Perforations/apertures are sometimes formed in such flexible films. Such perforations may be formed, for example, using laser systems and needle based systems. Conventional perforation systems tend to suffer from various deficiencies such as, for example: high cost of ownership; high cost of use; poor uniformity of perforations; poorly shaped perforations; etc.
Thus, it would be desirable to provide improved systems and methods of forming perforations/apertures in a flexible film.

Systems and methods for perforating flexible films, and related punching tools


In a hydraulic system several consumers (5'; 5"; 5'") are supplied by a common regulating pump (1). The regulating pump (1) is controlled as a function between the pump pressure (delta P) and the highest load pressure. This pressure difference (delta P.sub.max) is related to a minimum pressure difference (delta P.sub.min), and the comparison signal is input in a control unit (21) to influence the reference value signals (S1, S2, S3) by which the individual valves (6'; 6"; 6'") are controlled.

The present invention relates to a hydraulic system which is substantially free of instabilities in fluid flow arising from the load demand outstripping the capacity of the feed pump.
German Patent Publication DE 26 51 325 and corresponding U.S. Pat. No. 3,987,622 disclose a hydraulic system wherein the pressure extant at the pump as well as the highest load pressure are applied to a control valve. When the pump cannot furnish the volume flow required by the control valves and their associated consumers, the pressure difference between the pressure of the pump and the highest load pressure is reduced. As a result, the control valve reduces its supply to control pressure transducers by means of which the valves associated with the consumers are actuated. As a result, the flow through the valves is restricted. This restriction, however, becomes effective only when an excess demand already exists. When this restriction becomes effective, the consumers can no longer be controlled by means of their control valves.
In the system disclosed in German Patent Publication DE 35 46 336 and corresponding U.S. Pat. No. 4,759,183, the electrical control signals of the actuated multipleway valves are added. The volume flow which corresponds to the sum of the control signals is compared with the highest possible pump flow. When the sum of the control signals exceeds the possible pump flow, the control signals are reduced. In this system, it is necessary to evaluate all the control signals. Furthermore, it is necessary by means of a computer to take into consideration the dependence of the valve flows on the control signals.
It is the object of the invention to configure the hydraulic systems so that it is not subject to fluctuations, and that, moreover, it becomes possible to effect a desired weighting or apportioning and adjustment of the individual consumer flows relative to the operating parameters of the pump.


A computer method, apparatus and storage medium is provided for creating quantitative aesthetic graphics from data. The invention utilizes a graph algebra to construct graphs and visually or otherwise represents the graphs as a quantitative aesthetic graphic representation. To create the quantitative aesthetic graphics from data, the data is indexed to form a data set. Thereafter, the data is converted into a variable data structure composed of an index set, a range and a function. The variable data structure is converted into a variable set by using at least one of a blend step, a cross step and a nest step. The variable set is mapped into a set of points and the set of points is mapped into an aesthetic representation.

This invention relates generally to a computer method and apparatus for constructing graphs mathematically and aesthetically representing graphs as graphics, and more particularly to a computer method and apparatus for constructing graphs using a graph algebra and then visually or otherwise representing the graphs as a quantitative aesthetic graphic representation.
Until recently, graphics were typically drawn by hand to represent mathematical, statistical, and geometric relations. Computer graphics programs, particularly scientific and mathematical plotting packages, have made this task much easier but they have not altered its ad hoc aspect. Nor have statistical and mathematical packages that generate more complex graphics contributed to our understanding of how they are created.
A need exists for a computer method and system to be able to construct graphics systematically in order to handle more complex multivariate environments. This is also the case in connection with data mining computer systems. Unfortunately, the sophistication of data mining systems far exceeds the computer graphical methods used in their displays. Most data mining computer systems still rely on pie, line, and bar charts of slices of data cubes (multi-way aggregations of a subset of a database). These charts fail to reveal the relationships among the entities they represent because they have no deep grammar for generating them. They are simply hard-wired to facets of the data cube. For example, if one drills through the cube to view a different slice of the data, only a simple pie chart is obtained. A similar hard-wiring exists in displays from tree classifiers, neural networks, and other algorithms.
A need also exists for a method and apparatus for creating aesthetic graphics from data using graph algebra.
In accordance with the present invention, a computer method is provided for creating quantitative graphics using graph algebra.
In accordance with another aspect of the present invention, a data processing system is provided for constructing graphs mathematically using a graph algebra and displaying the graphs aesthetically as graphics, which can be a visual or other sensory display of the underlying mathematical graph.
In accordance with still another aspect of the present invention, a non-volatile storage medium is provided containing computer software encoded in a machine readable form for creating graphs mathematically using a graph algebra and for displaying the mathematical graph aesthetically, such as a visual representation.
In accordance with the invention, a method for creating quantitative graphics includes performing the following steps on a computer: indexing data to form a data set; converting the data set into a variable data structure, where the variable data structure is an index set; converting the variable data structure into a variable set by using at least one operation selected from the group consisting of a blend operator, a cross operator, and a nest operator; mapping the variable set into a set of points; and mapping the set of points into an aesthetic representation, which may be a visual graphic.
In accordance with another aspect of the present invention, a method is provided for creating quantitative graphics that includes the steps of: providing a list of variables; providing a list of representations for points; providing a list of coordinate systems; providing a list of aesthetic representations; selecting at least one variable from a list of variables; selecting at least one representation for points from the list of representations for points; selecting at least one coordinate system from the list of coordinate systems; selecting at least one aesthetic representation from the list of aesthetic representations; moving the at least one variable to a predetermined location; and displaying a visible graphic reflecting the at least one variable, the at least one representation for points, the at least one coordinate system and the at least one aesthetic representation.
In accordance with another aspect of the invention, the data processing system for constructing graphs mathematically and aesthetically representing the graphs as graphics includes: a computer processor; and a memory responsively coupled to the computer processor containing a set of computer instructions for: (a) indexing data to form a data set; (b) converting the data set into a variable data structure, where the variable data structure has an index set, a range and a function; (c) converting the variable data structure into a variable set by using at least one operator selected from the group consisting of a blend operator, a cross operator, and a nest operator; (d) mapping the variable set into a set of mathematical points; and (e) mapping the set of mathematical points into an aesthetic representation.
In accordance with still another aspect of the present invention, a non-volatile storage medium containing computer software encoded in a machine readable format for creating quantitative graphics is provided. The non-volatile storage medium includes: a set of computer instructions for indexing data to form a data set; a set of computer instructions for converting the data set into a variable data structure, where the variable data structure has an index set, a range and a function; a set of computer instructions for converting the variable data structure into a variable set by using at least one operator selected from the group consisting of a blend operator, a cross operator, and a nest operator; a set of computer instructions for mapping the variable set into a set of points; and a set of computer instructions for mapping the set of points into an aesthetic representation.
The methods, systems and devices in accordance with the invention allow data to be manipulated in many different ways and also represented by graphics in many different ways. Thus, the creation of graphics in accordance with the present invention is not limited by the constraints of graphical representations that are mere aggregations of a subset of a database.

Computer method and apparatus for creating visible graphics by using a graph algebra


Described herein are zymogens, methods of use for zymogens, and devices that incorporate zymogens. The zymogens include a substrate and an enzyme. The substrate can inhibit the enzyme and is a target for a protein produced by a microorganism. When the substrate is modified by a protein produced by a microorganism, the enzyme is activated. The zymogens can be used to amplify detection assays.

By amplifying chemical signals, a process that undergoes a chemical reaction can be detected, even at very low concentrations. Such an amplification process has the potential to provide great utility in any field that requires sensitive and/or fast detection of chemical reactions. For example, such a process could be used to detect microorganisms that cause infection and sickness, chemical or bio-warfare agents, or environmental pollutants.
Currently, there are no processes that provide for sensitive and fast detection of chemical reactions. Current methods are either too slow or not sufficiently sensitive. For example, some detection methods can detect the presence of harmful bacteria over the course of a few hours. However, it is often critical to detect pathogens within a few minutes in order to determine that a patient will have infection. The ability to detect the presence of harmful bacteria before the onset of infection would allow the healing of wounds and burns to occur both faster and with fewer complications. Furthermore, after patients are discharged from the hospital, they become responsible for monitoring their own healthcare, and the symptoms of infection may not be evident to the unskilled patient. Rapid identification of dangerous bacterial strains would allow the prescription of the most appropriate treatment and prevent the overuse of broad-spectrum antibiotics resulting in improved patient outcomes and a reduction in the development of antibiotic resistant strains of bacteria.
Severe burns are a major reason for admission to intensive care units. Currently, patients with total burns over 20% of body surface have a mortality rate of 22%. Although modern antimicrobial therapy has improved the outcome for serious burn patients, infections continue to be a major cause of morbidity and mortality in patients surviving the shock phase of a thermal injury. Despite antibiotic therapy and improved asepsis, often the control of infection is not completely successful. Infection is also one of the main causes of the patient's suffering, poor healing of wounds, extensive tissue destruction, and serious local and systemic complications. Therefore, control of infection in a severely burned patient plays an important role in prognosis, because the onset of serious infection may lead to the patient's death, either directly or through related mechanisms (e.g., the postponement of surgery because of poor general conditions).
Nosocomial infections are of serious concern for hospitals, as many patients are weak or immuno-compromised and susceptible to significant morbidity and mortality. Colonization rates are significantly higher in the hospital setting, both among healthcare workers, and among patients. Moreover, the colonizing organisms in the hospital environment are likely to be resistant to many forms of antimicrobial therapy, due to the strong selective pressure that exists in the nosocomial environment, where antibiotics are frequently used. It is estimated that there are more than 2 million hospital-acquired infections each year that could have been prevented by proper hand washing and rapid detection systems for microbial pathogens. These infections can be deadly to many patients. For example, elderly patients who develop a blood-borne infection due to catheterization have more than a 50% mortality rate. Unfortunately, many symptoms are only evident after the infection is already established.
The possibility that food or waterborne pathogens will be encountered in third world countries or unleashed in a bio-terrorism attack is problematic given the state of current technology. Many common causes of illness are capable of infecting the very young or elderly through contaminated water or food, even at very low concentrations (as few as 10 to 100 cells of Shigella, Salmonella, or E. coli O157:H7 can cause illness or death). A method that provides for early detection of such contaminants would be beneficial since current methods require a lengthy sampling and collection time to properly detect the presence and identity of pathogens. Early detection would reduce the number of food recalls and poor brand recognition (for example, when a processing plant is shut down by the USDA).
In this era of resistant bacteria and bio-weapons, the rapid detection and identification of human pathogens and biological toxins is crucial so that the most appropriate medical response can be implemented. Early detection requires some method of signal amplification, as biological agents can infect in such minute quantities that the agents may go unnoticed by other non-amplified techniques. It would be useful to have a signal amplification method that would surpass existing detection and identification systems in their speed and simplicity.

Signal amplification using a synthetic zymogen


This invention relates to tricyclic non-peptide vasopressin antagonists which are useful in treating conditions where decreased vasopressin levels are desired, such as in congestive heart failure, in disease conditions with excess renal water reabsorption and in conditions with increased vascular resistance and coronary vasoconstriction, the compounds having the general structure: ##STR1##

Vasopressin is released from the posterior pituitary either in response to increased plasma osmolarity detected by brain osmoreceptors or decreased blood volume and blood pressure sensed by low-pressure volume receptors and arterial baroreceptors. The hormone exerts its action through two well defined receptor subtypes: vascular V.sub.1a and renal epithelial V.sub.2 receptors. Vasopressin-induced antidiuresis, mediated by renal epithelial V.sub.2 receptors, helps to maintain normal plasma osmolarity, blood volume and blood pressure.
Vasopressin is involved in some cases of congestive heart failure where peripheral resistance is increased. V.sub.1a receptor antagonists may decrease systemic vascular resistance, increase cardiac output and prevent vasopressin induced coronary vasoconstriction. Thus, in conditions with vasopressin induced increases in total peripheral resistance and altered local blood flow, V.sub.1a receptor antagonists may be therapeutically useful agents. V.sub.1a receptor antagonists may decrease blood pressure, induce hypotensive effects and thus be therapeutically useful in treatment of some types of hypertension.
The blockade of V.sub.2 receptors is useful in treating diseases characterized by excess renal reabsorption of free water. Antidiuresis is regulated by the hypothalamic release of vasopressin (antidiuretic hormone) which binds to specific receptors on renal collecting tubule cells. This binding stimulates adenylate cyclase and promotes the cAMP-mediated incorporation of water pores into the luminal surface of these cells. V.sub.2 antagonists may correct the fluid retention in congestive heart failure, liver cirrhosis, nephritic syndrome, central nervous system injuries, lung disease and hyponatremia.
Elevated vasopressin levels occur in congestive heart failure which is more common in older patients with chronic heart failure. In patients with hyponatremic congestive heart failure and elevated vasopressin levels, a V.sub.2 antagonist may be beneficial in promoting free water excretion by antagonizing the action of antidiuretic hormone, On the basis of biochemical and pharmacological effects of the hormone, antagonists of vasopressin are expected to be therapeutically useful in the treatment and/or prevention of hypertension, cardiac insufficiency, coronary vasospasm, cardiac ischemia, renal vasospasm, liver cirrhosis, the syndrome of inappropriate anti-diuretic hormone secretion (SIADH), congestive heart failure, nephritic syndrome, brain edema, cerebral ischemia, cerebral hemorrhage-stroke, thrombosis-bleeding and abnormal states of water retention.
The following prior art references describe peptide vasopressin antagonists: M. Manning et al., J. Med. Chem., 35, 382(1992); M. Manning et al., J. Med. Chem., 35, 3895(1992); H. Gavras and B. Lammek, U.S. Pat. No. 5,070,187 (1991); M. Manning and W. H. Sawyer, U.S. Pat. No. 5,055,448(1991) F. E. Ali, U.S. Pat. No. 4,766,108(1988); R. R. Ruffolo et al., Drug News and Perspective, 4(4), 217, (May)(1991). P. D. Williams et al., have reported on potent hexapeptide oxytocin antagonists J. Med. Chem., 35, 3905(1992)! which also exhibit weak vasopressin antagonist activity on binding to V.sub.1 and V.sub.2 receptors. Peptide vasopressin antagonists suffer from a lack of oral activity and selectivity. Some exhibit partial agonist activity.
Non-peptide vasopressin antagonists have recently been disclosed, Y. Yamamura et al., Science, 252, 579(1991); Y. Yamamura et al., Br. J. Pharmacol, 105, 787(1992); J. D. Albright et al. U.S. Pat. No. 5,536,718A, U.S. Pat. No. 5,532,235A, U.S. Pat. No. 5,516,774A, U.S. Pat. No. 5,512,563A, U.S. Pat. No. 5,459,131A; A. Venkatessan et al. U.S. Pat. No. 5,521,173A; Ogawa et al., (Otsuka Pharm Co., LTD.) EP 0514667-A1, EPO 382185-A2, WO 9105549 and U.S.5,258,510, WO 9404525; Yamanouchi Pharm.Co.,Ltd., WO 9420473, WO 9412476, WO 9414796; Fujisawa Co. Ltd., EP 620216-A1; Ogawa et al, (Otsuka Pharm. Co.). EP 470514A disclose carbostyril derivatives and pharmaceutical compositions containing the same. Non-peptide oxytocin and vasopressin antagonist have been disclosed by Merck and Co.; M. G. Bock and P. D. Williams, EP 0533242A; M. G. Bock et al., EP 0533244A; J. M. Erb, D. F. Verber, P. D. Williams, EP 0533240A; K. Gilbert et al., EP 0533243A. U.S. Pat. No. 5,436,333 (Venkatesan et al.) teaches a process for the preparation of tricyclic heterocycles which are useful as intermediates in the production of cardiovascular agents.
The present invention relates to novel tricyclic derivatives which exhibit vasopressin antagonist activity, in vitro at the V.sub.2 receptors and exhibit in vivo vasopressin antagonist activity. In addition these compounds possess enhanced water solubility when compared to previously described 3-acylpyrrolobenzodiazepine derivatives.

3-Carboxamide derivatives of 5H-pyrrolo2,1-c!1,4!-benzodiazepines


Disclosed herein are integrated circuit (IC) packages with an electronic component having a patterned protective material on a face, as well as related devices and methods. In some embodiments, a computing device may include: an integrated circuit (IC) package with an electronic component having a protective material on the back face of the electronic component, where the protective material is patterned to include an area on the back face of the electronic component that is not covered by the protective material; a circuit board, where the IC package is electrically coupled to the circuit board; and a heat spreader, where the heat spreader is secured to the circuit board and in thermal contact with the area on the back face of the electronic component that is not covered by the protective material.

Electronic components, such as microprocessors and integrated circuits, generally produce heat. Excessive heat may degrade performance, reliability, life expectancy of an electronic component and may even cause component failure. Heat sinks, cold plates, and other similar thermal solutions are commonly used for dissipating heat and reducing the operational temperature of electronic components.

Integrated circuit packages with patterned protective material


The invention relates to a pressure cooking utensil comprising a vessel, a lid with an annular skirt, and a gasket interposed between the lid and the vessel, said gasket including a ring and a first lip in sealing contact with the top wall of the lid, said utensil being characterized in that it includes a leakage opening formed through said top wall, the annular skirt forming a stop abutment for the ring, said first lip presenting flexibility that is suitable, when the pressure that exists inside the enclosure exceeds a safety threshold, for causing the inside of the enclosure to communicate with the outside through the leakage opening.

The present invention relates to the general technical field of utensils for cooking food under pressure in a steam-filled atmosphere, preferably for home use, and in particular to a utensil of the kind known as a "pressure cooker" that is fitted with a sealing gasket put into place between the vessel and its lid in order to provide sealing, in operation, between the inside and the outside of the utensil, and thus allow pressure to rise inside the utensil.


A user of an automobile interactive onboard computer display monitors and controls battery power distribution during discharge. The user is enabled to interactively enter into a computer controlled display, proportions of the total battery power to be distributed to each of a set of devices. The distribution of the battery power to each of the devices is then monitored. The distribution of power to a specific device is halted when the power distributed to the specific device reaches the maximum of the proportion of the entered battery power to be distributed to the specific device.

Rechargeable batteries have been in use for almost as long as motor vehicles carrying such batteries have existed. For almost one hundred years, the discharge of charged automobile batteries has been monitored and responded to through the simplest of battery charge/discharge dashboard gauges. However, over the past generation, the distribution loads imposed upon automotive batteries during the discharge periods, when the battery is not being charged by automobile, have increased. Furthermore, the distribution of the battery power is becoming increasingly complex and hard to monitor. This leads to potential failures of battery functions that are essential to the automobile, such as power for the automobile starter.
In present day conventional motor vehicles, powerful audio systems consume battery power, as do television devices and heat/cool climate control devices. Hybrid automobiles that alternate battery power and combustion power, as needed, present an even greater need for controlling battery power distribution during discharge periods. Ultimately, the power distribution is critical in fully electrical automobiles wherein the automobile is running on the discharging of the charged battery.

Controlling the distribution of motor vehicle battery power to consuming devices during battery discharge

International Business Machines Corporation


The present invention relates to a method of inhibiting or preventing infection and blood coagulation in or near a medical prosthetic device after said device has been inserted in a patient comprising administering to the device a pharmaceutically effective amount of a composition comprising:

1. Field of the Invention
The present invention relates to a composition and method for the flushing and coating of catheters for the prevention of infection and blood coagulation.
2. Description of Related Art
Hemodialysis access systems for access to a human or animal patient""s vascular system for exchange of blood between the vascular system and an external processing apparatus are well known in the art. One method comprises a catheter placed in the patient with one end extending into the central venous system. As with any invasive procedure, the prevention of infection has been a problem, particularly with a device that must remain in place over protracted periods of time. Coagulation of the blood in and around the catheter has also proven troublesome and methods are needed for its prevention, particularly with regard to inhibiting the clogging of the catheter, which can diminish or destroy its usefulness. A significant amount of research has been directed to the alleviation of these problems.
It is standard procedure to flush catheters with an anticoagulant, such as heparin. However, heparin is not an antibacterial and, in addition, if not carefully controlled, it can carry the anti-coagulation process too far, thereby presenting a risk of hemorrhage.
U.S. Pat. No. 4,096,241 discloses pharmaceutical compositions for the treatment and for prophylaxis of tooth and gum infections, and in particular parodontosis, comprising derivatives of thiadiazine as the active ingredient.
U.S. Pat. No. 4,107,305 discloses a method of combating endotoxaemia by administering an effective amount of a taurolin composition.
U.S. Pat. No. 4,337,251 discloses the use of taurolin in humans or animals to eliminate or reduce adhesions after surgery.
U.S. Pat. No. 4,587,268 discloses a composition for the treatment of wounds comprising a resorbable aqueous gel having dissolved or dispersed therein one or more water-soluble medicaments, which are preferably an antibiotic or a methylol transfer antibacterial.
U.S. Pat. No. 4,587,284 discloses the preparation of an enhanced water-absorbency hydrophilic polymer material, suitable for use in wound dressings by a process in which a water-containing organic hydrogel comprising a gelable polysaccharide and/or protein or polypeptide interspersed with a polymer of a hydrophilic acrylic or methacrylic acid derivative is permeated with a base, the pH of said hydrogel being raised to at least 9 during treatment with said base.
U.S. Pat. No. 4,604,391 discloses the administration of taurolin compounds prophylactically to humans or warm-blooded animals to combat the occurrence of osteitis or osteomyelitis, especially in patients suffering from bone injuries of traumatic origin.
U.S. Pat. No. 4,626,536 discloses the use of taurolin compounds to combat toxic proteins or peptides, e.g., venoms, fungal toxins and bacterial exotoxins, in the bloodstream of humans or warm-blooded animals.
U.S. Pat. No. 4,772,468 discloses a pharmaceutical composition for filling into bone cavities comprising an aqueous paste formed from powdered calcium phosphate and an antibacterial substance, if necessary together with one or more binders. The antibacterial substance is preferably taurolidine and the calcium phosphate is preferably xcex2-tricalcium phosphate.
U.S. Pat. No. 4,797,282 discloses a drug depot, which can be implanted in the body, for the controlled, delayed release of cytostatics, comprising a synthetic material based on polyacrylates and/or polymethacrylates containing a cytostatic and at least one amino acid.
U.S. Pat. No. 4,853,225 discloses an implantable medicament depot useful for combating infections comprising physiologically acceptable excipients and at least one delayed release active compound that is a chemotherapeutic of the gyrase inhibitor type.
U.S. Pat. No. 4,882,149 discloses a pharmaceutical depot preparation for implantation into base tissue comprising natural bone mineral from which the naturally associated fat and bone-proteins have been removed whereby said bone is sterile and non-allergenic, said bone material having adsorbed thereon and/or absorbed therein one or more physiologically active substances. The physiologically active substance is advantageously an antibiotic or taurolidine or taurultam or a protein or polypeptide assisting bone regeneration.
U.S. Pat. No. 4,905,700 discloses an acoustic coupling medium for transmitting ultra-sound. The medium, which is of use in ultrasonic visualization of the human body, comprises a sheet of hydrogel containing over 90% water, preferably over 95% water. The hydrogel preferably comprises agar, the chains of which are interspersed with chains of polyacrylamide.
U.S. Pat. No. 4,960,415 discloses a device for inserting in wounds and wound cavities consisting of a container containing a pharmaceutically active substance, the walls of this container consisting at least partly of a membrane, preferably a semi-permeable membrane, which allows the active substance to escape into the wound area. The container is, more preferably, a dialysis tube. In order to drain off wound secretions, the container containing the pharmaceutically active substance, particularly taurolidine, is conveniently connected to a drainage tube. Preferably, a drainage tube is used in which the end that leads into the wound is split into filaments.
U.S. Pat. No. 5,077,281 discloses the use of taurolin compounds as blood coagulation-inhibiting agents and as a bacterial inflammation-inhibiting agents. According to the patent, taurolin has outstanding coagulation-inhibiting action and is especially suitable for use in medical conditions requiring dialysis and for vascular prostheses. It is also disclosed that these compounds can be used together with other anti-coagulants such as coumarin or heparin.
U.S. Pat. No. 5,167,961 and 5,417,975 disclose processes for the preparation of high purity bone mineral wherein the organic matter is degraded by heating with ammonia or a primary amine, characterized in that the solubilized degradation products are extracted by washing with flowing water at a temperature below 60xc2x0 C., such heating with primary amine and washing steps optionally being repeated, whereby substantially all organic matter removable by these steps is removed, the bone mineral so treated being heated in air at temperatures up to 700xc2x0 C.
U.S. Pat. No. 5,210,083 discloses an aqueous solution containing a bacterially effective concentration of taurolidine and/or taurultam together with a parenterally acceptable polyol. The aqueous solution is said to be particularly suitable for parenteral administration.
U.S. Pat. No. 5,362,754 discloses pharmaceutical compositions of a mixture of minocycline and EDTA (M-EDTA) and methods of using the compositions in maintaining the patency of a catheter port. Methods for inhibiting the formation of polysaccharide-rich glycocalyx (such as the glycocalyx of staphylococcal organisms) are also provided using an M-EDTA solution. The M-EDTA solution may also be used to pretreat a medical device to prevent adherence of infectious organisms, such as S. epidermis and S. aureous. The compositions destroy and prevent the formation of polysaccharide-rich glycocalyx.
U.S. Pat. No. 5,573,771 discloses a purified particulate bone mineral product for use in medicine, the particles of said mineral being substantially free from all endogenous organic material and having at least at the surface thereof resorbable, physiologically compatible, natural or synthetic macromolecular material. In particular, a bone mineral is provided that is impregnated with a gel-forming protein or polysaccharide such as gelatin to provide an increase in strength and a product comprising bone mineral in a matrix of collagen-fibers and a gel-forming protein. Such products are intended as remodeling implants or prosthetic bone replacement.
U.S. Pat. No. 5,593,665 discloses products containing tumor necrosis factor and taurolidine and/or taurultam as a combined preparation for simultaneous, separate or sequential use for treatment of patients suffering from medical conditions mediated by tumor necrosis factor.
U.S. Pat. No. 5,603,921 discloses a medicated dental floss for controlling the bacterial activity associated with gingivitis. The floss incorporates an antimicrobial agent which, as a result of the flossing action, is deposited to the interdental area of the teeth. The slow dissolution of the antimicrobial agent ensures that effective levels of medication are attained for sustained periods, thereby reducing bacterial activity.
U.S. Pat. No. 5,688,516 discloses compositions and methods of employing compositions in flushing and coating medical devices. The compositions include selected combinations of a chelating agent, anticoagulant, or antithrombotic agent, with a non-glycopeptide antimicrobial agent, such as the tetracycline antibiotics. Methods for using these compositions for coating a medical device and for inhibiting catheter infection are also disclosed. Particular combinations include minocycline or other non-glycopeptide antimicrobial agent together with EDTA, EGTA, DTPA, TTH, heparin and/or hirudin in a pharmaceutically acceptable diluent.
Myers et al., J. Appl. Bacteriol 48:89-96 (1980) reported that taurolinxe2x80x94bis(1,1-dioxo -perhydro-1,2,4 thiadiazinyl) methanexe2x80x94is an antimicrobial compound formed by the condensation of two molecules of taurine with three of formaldehyde. It had been previously suggested that taurolin releases formaldehyde in contact with bacteria. The authors presented evidence that indicated that taurolin is mostly hydrolyzed in aqueous solution to release one molecule of formaldehyde and two monomeric molecules, 1,1-dioxo-perhydro-1,2,4-thiadiazine and its carbinolamine derivative. According to the article, a stable equilibrium was established. The authors concluded that antibacterial activity was not entirely due to adsorption of free formaldehyde, but also to reaction with a masked (or latent) formaldehyde, as the activity of taurolin was found to be greater than formaldehyde. The monomer was found to be only slightly active by comparison.
Gorman et al., J. Clin. Pharm. Ther. 12:393-399 (1987) reported on the examination of three antimicrobial agents, taurolidine, chlorhexidine, and povidone-iodine for microbial anti-adherence activity. Two adherence systems were investigated: an oral isolate of Candida albicans to human buccal epithelial cells and a urine isolate of E. coli to human uroepithelial cells. Each of the three agents exhibited significant anti-adherence activity, which was concentration dependent.
Root et al., Antimicrobial Agents and Chemotherapy 32(11):1627-1631 (1988) reported that granulocytopenic patients with an intravascular catheter are at increased risk for infection with S. epidermis. During the intervals when the catheters are not being used for infusions, it is customary to maintain patency of the catheter lumen with a solution containing heparin. The authors showed that heparin does not inhibit the growth of S. epidermis isolated from the catheter of an infected patient. A 20-mg/mL solution of disodium EDTA, a chelating agent that effectively anticoagulates blood at this concentration, was shown to be bactericidal for an initial inoculum of 103 CFU of staphylococci per mL in 24 hours. Vancomycin, an antibiotic that is often employed to treat Staphylococcus infections was also found to be bactericidal for initial inocula of 103 CFU/mL at doses of 6.7 xcexcg/mL, a drug concentration in the therapeutic range. The authors recommended that EDTA be studied as a replacement for heparin solutions for the maintenance of intravenous catheters in granulocytopenic patients, in view of its low cost, effectiveness as an anticoagulant, and bactericidal activity.
Jones et al., J. Appl. Bacteriol. 71:218-227 (1991) examined the effects of three non-antibiotic, antimicrobial agentsxe2x80x94taurolidine, chlorhexidine acetate, and povidone-iodinexe2x80x94on the surface hydrophobicity of the clinical strains E. coli, S. saprophyticus, S. epidermidis, and C. albicans. At concentrations reported to interfere with microbial-epithelial cell adherence, all three agents were found to alter the cell surface hydrophobicity. However, these effects failed to exhibit a uniform relationship. Generally, taurolidine and povidone-iodine treatments decreased the hydrophobicity of the strains examined, whereas chlorhexidine acetate effects depended upon the micro-organism treated.
Traub et al., Chemotherapy 39:322-330 (1993) examined taurolidine for bactericidal activity against a representative number of multiple-antibiotic-resistant bacterial isolates in broth as well as in the presence of bovine and human serum and fresh defibrinated human blood. The authors suggested that this antimicrobial substance might be employed for topical treatment of patients colonized or superficially infected by glycopeptide-resistant strains of E. faecium, S. aureus (GRMRSA), or by Enterobacteriaceae producing wide-spectrum xcex2-lactamases.
Willatts et al., Crit. Care Med. 23(6):1033-1039 (1995) reported that taurolidine had no beneficial therapeutic effect on the outcome of patients admitted to the intensive therapy unit of a university teaching hospital with sepsis syndrome, using clinical, bacteriologic outcomes, progression of endotoxemia, resolution of organ failure, and 28-day mortality rate as end points.
Darouiche et al., Nutrition 13(4)(suppl):26S-29S (1997) reported that the prevention of vascular catheter-related infection mostly centers around inhibiting the adherence to the catheter of microorganisms originating from either the skin or the catheter hub. They described two general approaches that can be used non-exclusively for the successful prevention of vascular catheter-related infection. The first approach does not use antimicrobial agents and includes measures such as placement and maintenance of vascular catheters by a skilled infusion therapy team and use of maximal sterile barriers. The second approach uses antimicrobial agents and involves the application of topical disinfectants such as chlorhexidine, use of silver-impregnated subcutaneous cuffs (for short-term central venous catheters), flushing catheters with a combination of antimicrobial and antithrombic agents, and coating of catheters with either antiseptic (chlorhexidine and silver sulfadiazine) or antimicrobial agents (minocycline and rifampin).
In a talk presented at the 30th annual meeting of the American Society of Nephrology, held Nov. 2-5, 1997 in San Antonio, Tex., Sodemann et al. reported on a four year trial of a gentamicin/sodium citrate mixture as an antibiotic-lock technique for salvage and prevention of catheter-related infections. They concluded that the replacement of catheters due to infection can be avoided by routine application of the concentrated gentamicin/citrate mixture and that even the salvage of intraluminally contaminated catheters is possible.
Notwithstanding the above-described contributions to the art, a need continues to exist for a safe and effective method for the prevention of infection and blood coagulation in patients whose illness requires the implantation of atrial catheters.
In accordance with the present invention, compositions are provided that comprise an anticoagulant and a non-antibiotic biocide, neither of which have the properties of (a) inducing bacterial resistance and (b) causing systemic effects in the event of accidental overdose, i.e., there are no systemic anti-clotting and no systemic biocidal effects.
As employed herein, the term xe2x80x9canticoagulantxe2x80x9d is intended to mean any composition that has the ability, either directly or indirectly, to prevent the coagulation of blood or to dissolve blood clots or other coagulated species once formed.
The biocide employed in the practice of the present invention is one that is a xe2x80x9cnon-antibiotic,xe2x80x9d i.e., it is not an antibiotic. For purposes of the present invention, the term xe2x80x9cantibioticxe2x80x9d is defined as a chemical substance produced by a microorganism that has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. It is an object of the present invention to avoid these antibioticsxe2x80x94although they may, if desired, be present in addition to the non-antibiotics of the inventionxe2x80x94in order to minimize the probability of producing microorganisms that are genetically immune thereto. antimicrobial/anti-coagulant compositions are provided for use in flushing and coating medical prosthetic devices, especially catheters and ports.
Specifically, the present invention relates to a method of inhibiting or preventing infection and blood coagulation in or near a medical prosthetic device after said device has been inserted in a patient comprising administering to the device a pharmaceutically effective amount of a composition comprising:
(A) at least one taurinamide derivative, and
(B) at least one compound selected from the group consisting of biologically acceptable acids and biologically acceptable salts thereof, whereby there are no systemic anti-clotting and no systemic biocidal effects.
More particularly, the present invention is directed to a method of inhibiting or preventing infection and blood coagulation in or near a medical prosthetic device after said device has been inserted in a patient comprising administering to the device a pharmaceutically effective amount of a composition comprising:
(A) at least one antimicrobial compound of the formula
wherein R1 is hydrogen or alkyl and R2 is hydrogen, alkyl, or a group of the formula
and
(B) at least one compound selected from the group consisting of biologically acceptable acids and biologically acceptable salts thereof.
In another embodiment, the present invention is directed to a medical prosthetic device coated with a composition comprising:
(A) at least one antimicrobial compound of the formula
wherein R1 is hydrogen or alkyl and R2 is hydrogen, alkyl, or a group of the formula
and
(B) at least one compound selected from the group consisting of biologically acceptable acids and biologically acceptable salts thereof, wherein the composition is included in a pharmaceutically effective amount for preventing or inhibiting infection and blood coagulation.
In still another embodiment, the present invention is directed to a medical prosthetic device prepared by a process comprising exposing the medical prosthetic device to a composition comprising: (A) at least one antimicrobial compound of the formula
wherein R1 is hydrogen or alkyl and R2 is hydrogen, alkyl, or a group of the formula
and
(B) at least one compound selected from the group consisting of biologically acceptable acids and biologically acceptable salts thereof, wherein the composition is included in a pharmaceutically effective amount for preventing or inhibiting infection and blood coagulation.
As stated above, the present invention is directed to a method of inhibiting or preventing infection and blood coagulation in or near a medical prosthetic device after said device has been inserted in a patient comprising administering to the device a pharmaceutically effective amount of a composition comprising:
(A) at least one antimicrobial compound of the formula
wherein R1 is hydrogen or alkyl and R2 is hydrogen, alkyl, or a group of the formula
and
(B) at least one compound selected from the group consisting of biologically acceptable acids and biologically acceptable salts thereof.
The preparation of representative examples of the compounds of formula I is described in U.K. Pat. No. 1,124,285. Basically, these compounds are condensation products of taurinamide and formaldehyde and, therefore, will be referred to herein as xe2x80x9ctaurinamide derivatives.xe2x80x9d They are active not only against both gram-positive and gram-negative bacteria, but also against exotoxins and endotoxins produced by these organisms.
Where R1 and/or R2 are alkyl, they may be either straight or branched chain alkyl and are preferably independently selected from those alkyls having from 1 to 8 carbon atoms, i.e., methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, and isomers thereof. More preferably, where R1 and/or R2 are alkyl, they are independently selected from those alkyls having from 1 to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, and isomers thereof More preferably, where R1 and/or R2 are alkyl, they are independently selected from those alkyls having from 1 to 6 carbon atoms, i.e., methyl, ethyl, propyl, butyl, pentyl, hexyl, and isomers thereof; most preferably, the alkyl group(s) have from 1 to 4 carbon atoms, i.e., methyl, ethyl, propyl, butyl, and isomers thereof. It is, however, most preferred that R1 be hydrogen and that R2 be hydrogen or a group of formula II.
In the present invention, of the compounds of formula I, the compounds taurolidine (R1=H; R2=formula II) and taurultam (R1xe2x95x90R2xe2x95x90H) are particularly preferred. Taurolidine is bis-(1,1-dioxo-perhydroxy-1,2,4-thiadiazin-4-yl)methane.
The antimicrobial compound employed in the practice of the present invention is a formaldehyde carrier, i.e., a non-toxic derivative containing formaldehyde in combination.
The mode of action of taurolidine has been shown to include the transfer of methylol groups to hydroxyl or amino groups present on the above toxins or on the mureine of the bacterial cell walls. In solution, taurolidine exists in equilibrium with taurultam and N-methylol taurultam, taurolidine being greatly predominant. Taurultam is itself in equilibrium with methylol taurinamide, the equilibrium being greatly in favor of taurultam. When the above methylol derivatives, methylol taurultam and methylol taurinamide, contact the toxins or bacteria, methylol groups are transferred. Methylol taurultam is thereby converted to taurultam, while methylol taurinarnide is converted to taurine, a naturally occurring aminosulfonic acid that is extremely well tolerated in the human body. It will thus be appreciated that taurolidine and taurultam act in essentially the same way and produce the same final products.
Bacterial infections by gram-negative organisms are commonly accompanied by endotoxaemia, that is, by the reaction of the patient to the endotoxin liberated by the organisms.
Endotoxin is a complex lipopolysaccharide constituent of the O-somatic antigen and is loosely attached to the cell walls of gram-negative bacteria. Irrespective of the bacterial source, all endotoxins exhibit similar toxic propertiesxe2x80x94in contradistinction to the exotoxins of gram-positive bacteria, which exert a wide range of individual effects. In man, it can produce the syndrome of endotoxin shock when large numbers of gram-negative bacteria are lysed. This syndrome is encountered in about 30% of patients with gram-negative septicaemia. It is known that endotoxins can be inactivated by taurinamide derivatives.
Toxic proteins, such as, exotoxins, can similarly be inactivated and methylol transfer antibacterials can be administered to combat toxic proteins in the absence of lipopolysaccharide toxins. Toxins that may be concerned include the exotoxins of such gram-negative bacteria as E. coli and Bacteroides fragilis. It is known that intravenous administration to mice of 0.2 mL of a 20% solution of taurolidine in sterile 5% polyvinyl pyrrolidone can very significantly reduce the mortality rate on intraperitoneal administration of pathogenic strains of both E. coli and B. fragilis.
Other toxic proteins include venoms such as mellitin and fungal toxins such as amanitin and xcex1-bungarotoxin, which have been shown to be substantially detoxified by taurolidine.
A particular advantage of taurolidine is its very low toxicity; it has been shown to be non-teratogenic in mice, the intraperitoneal LD50 being on the order of 1.5 g/kg. As mentioned above, these compounds exhibit methylol transfer activity that results in the production of taurine, which is found naturally in the body and is particularly nontoxic. A further advantage of taurolidine is its stability in aqueous solution, enabling the solutions to be pre-packed and stored over relatively long periods.
The taurinamide derivatives employed in the practice of the present invention will normally be administered as an aqueous solution by injection into the medical prosthetic device. Such solutions may contain, in addition to a given taurinamide derivative, gentamycin sulfate or chondroitin sulfate and also may commonly contain a solubilizing agent, such as, polyvinyl pyrrolidone (PVP), to help maintain the taurinamide derivative in solution and to contribute to the isotonicity of the solution. The concentration of the taurinamide derivatives in such solutions can range from greater than zero to about 2 wt %; concentrations in the range of from about 0.01 to about 1.5 wt % are preferred; and a concentration of about 1 wt % is most preferred. Higher concentrations than these would be useful, but in such cases, solubility becomes a problem.
Where PVP is incorporated into the solution, it will commonly be employed at a concentration in the range of from 4 to 7% by weight in order to achieve relatively high concentrations of the taurinamide derivatives, especially taurolidine, which have low water solubility. The molecular weight of the PVP should not be greater that about 30,000 and is preferably less than 10,000, e.g., between about 200 and 3500. Kollidone(copyright) 17, sold by BASF is especially suitable. Such PVP is fairly quickly absorbed and excreted through the kidneys.
The amount of solution of taurinamide derivative injected into a medical prosthetic device will be enough to fill it. Such devices, when they are hemodialysis catheters, typically have internal volumes in the range of from about 0.1 mL to about 10 mL; such quantities will, of course, vary with the length and diameter of the tubing of the device, which, inter alia, can be a function of the size of the individual patient.
The concentration of the taurinamide derivative in such solutions is preferably in the range of from about 0.4 to about 5% by weight, depending, at the maximum, upon the solubility of the compound. Solutions of about 0.4 to about 2.0 weight % taurolidine, i.e., about 4 to about 20 grams per liter, are particularly preferred.
An example describing the preparation of a stock solution of taurolidine has appeared in several patents, for example, U.S. Pat. No. 4,337,251:
15 Liters of double distilled pyrogen free water are filled into a 25 liter glass vessel equipped with a stirrer and an intensive reflux device and heated to 50xc2x0 C. with stirring. Taurolidine (400 g) is added followed by PVP (Kollidone 17; 1000 g). After dissolution, the solution is cooled and the pH is adjusted to 6.0 with a few drops of 0.1 N hydrochloric acid. The solution is then passed through an adsorption filter to remove microorganisms and pyrogens and through a sterilizing Millipore filter before being filled into 100 mL vials, which are finally autoclaved.
If desired, some or all of the PVP may be replaced by a parenterally acceptable polyol. This use for polyols has been disclosed in U.S. Pat. No. 5,210,083, the disclosure of which is incorporated herein by reference in its entirety. There, it is pointed out that at higher concentrations of taurolidine, crystallization can occur, which can render the solution unuseable.
In the case of bacteria and their endo- and exotoxins, it has been found that after the methylol transfer, as described above, there is a further irreversible step involving dehydration. Thus, in the case of bacterial endotoxins, which are lipopolysaccharides, it was found that an irreversible cross-linking reaction takes place that prevents the endotoxin from exerting its lethal effect. Similarly, in the case of bacterial exotoxins, which are proteins or polypeptides and do not contain lipopolysaccharide material of the kind found in the endotoxins , the detoxification reaction has been found to be irreversible. However, it is disclosed in U.S. Pat. No. 5,210,083 that the transfer of methylol groups by the mechanism set out above is reversible in the case of many hydroxyl or amino compounds, so that an equilibrium can be established that does not significantly interfere with the availability of taurolidine. Thus, polyols, such as, sugars and sugar alcohols, can also be used to maintain relatively high concentrations of taurolidine and/or taurultam in aqueous solution without significantly affecting their antibacterial and antitoxin activity. Preferred polyols include carbohydrates, e.g., hexoses, such as, glucose, fructose, and mixtures thereof; pentoses, such as, xylose; polysaccharides, such as, dextran or hydrolyzed starch; glycerol; and sugar alcohols, such as, sorbitol, mannitol, and xylitol. Glucose is most preferred.
The concentration of the polyol is typically in the range of from about 3 to about 40% by weight. In the case of glucose, the concentration is preferably in the range of from about 10 to about 30% by weight, more preferably about 20%.
Where such polyols are used, the concentration of taurolidine in the solution is preferably in the range of from about 0.5 to about 5%, more preferably in the range of from about 2 to about 3% by weight. The concentration of taurultam is preferably in the range of from about 1 to about 7.5%, more preferably in the range of from about 3 to about 5% by weight.
Since gram-negative organisms will frequently be present and since the bacteriostatic activity of the taurinamide derivatives is lower than that of many conventional antibiotics, it may be advantageous to administer the compositions employed in the practice of the present invention in conjunction with a broad spectrum antibiotic substance, more especially, a substance strongly active against both gram-positive and gram-negative pathogens that, preferably, induces no or only delayed resistance, for example, a xcex2-lactam antibiotic, such as, penicillin, ampicillin, or cephalosporin; a tetracycline antibiotic; a macrolide antibiotic, such as, erythromycin; a polypeptide antibiotic, such as, bacitracin or novobiocin; or, more preferably, an aminoglycoside antibiotic, such as, amikasin, butirosin, fortimycin, streptomycins, neomycin, linkomycins, such as, clindamycin and lincomycin, kanamycin, dideoxykanamycin B (DKP), lividomycin, netilmicin, ribostamycin, sagamycins, seldomycins and their epimers, sisomycin, sorbistin, tobramycin, vancomycin, gentamicin, and rifamycins, such as, rifampicin and rifamycin; and the like. Of these, gentamicin is preferred.
However, antibiotics are often contraindicated for use in surgical treatment, owing to their tendency to produce resistant strains, and, except in unusual cases, it is preferred that the taurinamide derivative be relied upon solely for antibacterial action, since such derivatives do not produce resistant strains.
The composition employed in the practice of the present invention preferably also contains a pharmacologically acceptable carrier solution, such as, water, Ringer""s solution, or saline. Additionally, the compositions of the present invention can also contain other dissolved additives that can favorably influence their physical and biochemical properties, for example, amino acids, sugar, common salt, fats, lipids, and the like.
The antimicrobial taurinamide derivatives employed in the practice of the present invention are used in combination with a biologically acceptable acid or a biologically acceptable salt thereof. It is preferred that the acid be a carboxylic acid and more preferred that it also be an anticoagulant. U.S. Pat. No. 5,077,281 teaches that taurolin compounds exhibit outstanding coagulation-inhibiting action in their own right and are especially suitable for use in medical conditions requiring dialysis and for vascular prostheses, either alone or in combination with other anti-coagulants such as coumarin or heparin. As pointed out in the patent, this is contrary to the teaching of xe2x80x9cTaurolinxe2x80x9d, published by W. L. Bruckner and R. W. Pfirrmann, Verlag Urban und Schwarzenberg, Munich, 1985, which expressly states that taurolin does not influence blood coagulation and displays no anti-phlogistic action. It is the belief of the present inventor that the taurinamide derivatives employed in the practice of the present invention do exhibit a degree of anticoagulant activity, although to a lesser extent than is found with better known anticoagulants, such as heparin. Accordingly, it is beneficial to employ the taurinamide derivatives in combination with an anticoagulant, preferably one that is a biologically acceptable acid or salt thereof.
In accordance with the present invention, beneficial results are achieved when the antimicrobial taurinamide derivatives are combined with a biologically acceptable acid or biologically acceptable salt thereof so as to produce a pH for the ultimate composition that is no higher than 7, preferably in the range of from about 3.5 to about 6.5, more preferably in the range of from about 4.5 to about 6.5. Exemplary of such acids are acetic acid, dihydroacetic acid, benzoic acid, citric acid, sorbic acid, propionic acid, oxalic acid, fumaric acid, maleic acid, hydrochloric acid, malic acid, phosphoric acid, sulfurous acid, vanillic acid, tartaric acid, ascorbic acid, boric acid, lactic acid, ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis -{xcex2-aminoethyl ether}-N,N,Nxe2x80x2,Nxe2x80x2-tetraacetic acid, and diethylenetriamine pentaacetic acid, esters of p-hydroxybenzoic acid (Parabens), and the like, and biologically acceptable salts of the foregoing, such as, ammonium phosphate, potassium citrate, potassium metaphosphate, sodium acetate, sodium citrate, sodium lactate, sodium phosphate, and the like. A blood anticoagulating amount of an acid selected from the group consisting of citric acid, phosphoric acid, ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis-{xcex2-aminoethyl ether}-N,N,Nxe2x80x2,Nxe2x80x2-tetraacetic acid, and diethylenetriamine pentaacetic acid and biologically acceptable salts thereof is preferred. It is preferred that the acid employed in the practice of the present invention be an organic acid, especially one having at least one carboxyl group, particularly citric acid or EDTA. It is more preferred that the acid be citric acid and most preferred that it be used in combination with a citrate salt, e.g., sodium citrate, since, in addition to its pH lowering and anticoagulation capabilities, it is also known to be an antiseptic at the 3% level.
Mermel, L. A. et al., in a talk entitled Taurolidine Activity Against Vancomycin-Intermediate Susceptibility Staphylococcus Aureus (VISA) and Methicillin-Resistant Staphylococcus Aureus (MRSA) presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (1998), disclosed that taurolidine activity increases with decreasing pH in the range of from pH 7.0 to pH 5.0.
EDTA is a known anticoagulant that is used in blood collection tubes. It is also known to have the ability to form chelates with calcium. Since calcium is one factor that is known to have a role in the coagulation of blood, it is believed possible that at least part of EDTA""s efficacy in anticoagulant activity may be brought about by this means. Sodium citrate is also believed to have anticoagulation properties by virtue of its ability to generate insoluble calcium citrate.
Ethylene glycol-bis-{xcex2-aminoethyl ether}-N,N,Nxe2x80x2,Nxe2x80x2-tetraacetic acid (EGTA) and diethylenetriamine pentaacetic acid (DTPA) and salts thereof are other known chelating agents that can be used in place of, or in addition to, EDTA or citric acid/citrate.
The foregoing anticoagulants can be used alone in the free acid state, but, more often will be employed with some or all of their carboxylic acid groups neutralized with an appropriate base or combined with a similar salt. Generally, it will be desirable to employ a cation that will form a salt that is soluble in aqueous solution, such as alkali metal ions, e.g., sodium, potassium, or lithium. Zinc citrate may also be employed. Sodium or potassium salts are normally preferred, especially sodium, and the disodium salt of EDTA and sodium citrate are most preferred.
The acid and/or salt will be used in a concentration effective to bring about the desired anticoagulation effect and, at the same time, bring about, or help to bring about, an appropriate pH for biological use. Typically, the combined antimicrobial and anticoagulant composition of the present invention will have a pH in the range of from about 3.0 to about 7, preferably from about 3.5 to about 6.5 and, most preferably from about 4.5 to about 6.5. The composition will normally be at a physiological pH. If necessary, the pH can be adjusted by additional acid or base, such as a mineral acid, for example hydrochloric acid, or, preferably, one that will not cause acidosis, such as, for example, acetic, malic, or lactic acid. Other methods for adjusting the pH, familiar to those of skill in the art, can also be employed. Where, as is preferred, trisodium citrate and citric acid are employed in the practice of the present invention, the trisodium citrate will typically be used in a concentration range of from about 5 to about 50 grams per liter. The citric acid will then be added in sufficient amount to bring the pH to the desired level.
Although the process of the present invention is primarily concerned with introducing the antimicrobial/anticoagulant compositions into catheters that are already in place, those skilled in the art will understand that contacting an artificial surface outside the body with these compositions can prevent the deposition of blood coagula on such surface after its implantation and aid in the elimination of sites for bacterial growth. Thus, the surfaces of medical devices, such as hemodialysis catheters, can be pre-treated by the compositions employed in the practice of the present invention to prevent the blockage due to blood coagula that present a favorable site for bacteria growth and thereby prevent the infection that may ensue. The apparatus can be treated with a composition initially and then, after insertion, repeated periodic flushing as referred to above.
Although the process of the present invention is primarily and preferably directed to maintaining the patency and asepsis of implanted hemodialysis catheters, beneficial effects may also be obtained in applying the process to other, similar, devices, such as, central venous catheters, peripheral intervenous catheters, arterial catheters, Swan-Ganz catheters, umbilical catheters, percutaneous nontunneled silicone catheters, cuffed tunneled central venous catheters as well as with subcutaneous central venous ports.
Various features and aspects of the present invention are illustrated further in the examples that follow. While these examples are presented to show one skilled in the art how to operate within the scope of the invention, they are not intended in any way to serve as a limitation upon the scope of the invention.

Coatings and soaks for medical prosthetic devices comprising taurinamide derivatives and carboxylic acids and/or salts thereof


A system and method of detecting air vortexing and coriolis effect vortex-created cavitation in a shutdown cooling system drain pump of a nuclear power plant during midloop operation where the plant includes a horizontal hot leg having a drain pipe connected from the lower region thereof to a drain pump which includes attaching transducers of a portable clamp-on ultrasonic flowmeter to the drain pipe to measure and detect flow-void-created disruptions in the flowmeter ultrasonic signal and providing a remote alarm triggered by the disrupted signal.

In a nuclear plant of the pressurized water reactor (PWR) type, coolant fluid, which is basically boron and water, is continuously transferred through a closed circulation loop between a nuclear reactor and one or more steam generators.
During power production, the pressurized coolant absorbs heat released by the thermonuclear reaction occurring in the reactor. The heated coolant then flows through a main pipe which is appropriately known as the "hot leg" of the circulation loop. The hot leg delivers the hot coolant to a steam generator.
In the steam generator, the coolant fluid circulates through a heat exchanger. The heat exchanger cools the coolant fluid and uses the heat removed from the coolant to produce steam. This steam is eventually used to drive turbines and generate electricity.
After the circulating coolant is cooled by a heat exchanger, a circulation pump removes the coolant from the steam generator via a "suction leg" and returns it to the reactor via a "cold leg" and inlet. The coolant is then reheated in the reactor and the cycle repeats.
This circulation of coolant through one or more loops is critical for the operation of the power plant. Not only does it deliver heat energy to the steam generators where the energy is used to produce steam for driving the turbines, but the circulating coolant also prevents the reactor core in the reactor from over-heating.
Nuclear power plant systems, including the steam generators, require periodic maintenance. In particular, the fluid circulation system must be inspected for potential degradation and nozzle dams must be installed and removed from the steam generators to allow inspection and maintenance to be performed in a dry environment.
In order to install and remove nozzle dams, the coolant fluid must be drained from the steam generator. This requires lowering the fluid level in the main circulation loop and consequently the hot leg or main pipe. During such a maintenance period, which is termed a "shutdown", the coolant continues to be heated by decay heat from the reactor core but it is cooled by an alternate heat exchanger and auxiliary circulatory system know as the "shutdown cooling system".
In order to lower the coolant or water level in the shutdown reactor system to allow maintenance operations on portions of the system above the lowered water level, the water level must be controlled and maintained at a minimum level and flow rate to continuously provide adequate core cooling. This minimum level is about midway within the reactor coolant system main loop piping (the hot leg) and is commonly referred to as "midloop".
During midloop operation, coolant water is circulated through the system to cool the core. Typically, there is a drain line or lines which communicate with the lower region of one or more of the main loop pipes or legs to draw the heated water from the core for cooling by the alternate heat exchanger in the shutdown cooling system and subsequent recirculation of cooled water to a reactor inlet and thus to the core.
It is possible to experience the formation of a coriolis effect vortex in the drain line during midloop operation if the water level is lowered too far down or if the drain flow rate is too high. Such a vortex is undesirable because it limits the rate at which coolant flow can be drained from the system and it can eventually lead to cavitation in the drain pump. Both results cause concern for continued cooling of the core.
The current methods to avoid vortex formation attempt to keep the water level as high as possible and/or reduce the flow rate, resulting in a conflict between the need to lower the water level for maintenance service, and the need to keep the water level high and at a sufficient rate for safe core cooling.
Midloop measuring systems in use are related to a detection of the water elevation and inference of the status of the vortex therefrom. Co-pending U.S. patent application Ser. No. 08/783,978, assigned to the same assignee as the instant application and filed Jan. 15, 1997, is for a system which reduces pump cavitation by inserting a vortex breaker in the drain pipe adjacent the main pipe or hot leg.
In nuclear power plants much attention has been given to shutdown cooling system reliability, especially during reactor coolant system midloop water level operation. Midloop operation in a typical pressurized water reactor (PWR) nuclear steam supply system, for example, for the installation and removal of steam generator nozzle dams, can be a very difficult operational process. In fact, typically, the water level allowed tolerance is approximately plus or minus one inch (.+-.1"). The plant operator must control this water level manually. Current instruments used measure only the average reactor coolant system (RCS) water level and the shutdown cooling pump current.
The RCS water level measurement accuracy is limited by the instrument technology used and process parameter changes such as temperature, pressure and boric acid concentration. The shutdown cooling pump current measurement alarm occurs only after air has already been ingested into the pump, thus it cannot be used to avoid the air vortex.

Shutdown cooling pump vortex detection system


A method, apparatus, and system for accounting for dark current in the output of an imaging array is presented. A dark current monitor on the monolithic semiconductor imaging array is provided. The dark current monitor may be darkened pixels of the imaging array, darkened pixels of another array, or a temperature monitor and associated circuitry necessary to calculate relative dark current from the monitored temperature.

Modern imaging systems using charged coupled device (CCD) arrays and complementary metal oxide semiconductor CMOS arrays have come into increasing use for both industrial and consumer applications. CCD arrays have a longer history and much more time to solve problems arising in manufacture and use. CCD arrays have fewer dark current problems than CMOS arrays. However, CMOS arrays promise less expensive imaging, principally because other functions may be combined on the semiconductor substrate and the well honed techniques developed for computer technology may be used to produce the arrays.
Prior art CMOS arrays have an array of pixels arranged in rows and columns, where light is absorbed in the semiconductor substrate to generate electrons, and the electrons are stored until they are "read out" to generate an image. The charge stored for one pixel is generally sent through a column amplifier to generate a voltage, which is then converted to a digital signal in an analog to digital converter (ADC). The ADC has a minimum signal input Vmin below which a zero is generated, and a maximum signal input Vmax which saturates the ADC. Each column amplifier generally has an offset voltage which is added to the signal from the stored electrons, so that the signal sent to the ADC is Vmin if no light is incident on the pixel and no electrons are stored. Since the amplification is slightly temperature and process dependent, the offset voltage must be adjustable, and means provided to send a "zero" or "dark" signal to the column amplifier so that the offset may be set to a voltage slightly less than Vmin. The "dark" signal may be sent by dummy pixels which in effect ground the input to the amplifier.
However, electrons are generated in the pixel without light by spontaneous means which are generally exponentially dependent on the temperature of the semiconductor material of the pixel. The electrons so generated give rise to "dark current". Most light sensors produce "dark current". The prior art of CMOS image arrays is deficient in that the "dark current" is not accounted for in the case that the array temperature, and also the variation in temperature over the array, changes with time. For the case of a CMOS integrated circuit application, where many functions are carried out on a monolithic semiconductor chip, this is a serious deficiency. Each part of the chip produces a different amount of heat at different times. Part of the array may be near a section of the chip having a dense array of devices liberating a large amount of heat, so that parts of the array will have a large temperature difference with respect to other parts of the array. The temperature and variation in temperature may change as the device is used for imaging, so that the dark current contribution to the image is variable and unaccounted for.

Integrated CMOS imaging array dark current monitor


A removing tool for car-window edge strips includes a grip, a linking rod, a protective disc and a tool set. The protective disc is positioned between the grip and the linking rod, and the linking rod has a flat insert groove diametrically formed vertically for the tool set to insert therein and kept tight by screws. The protective disc can protect hands of a user from getting hurt during removing operation. The flat insert groove of the linking rod can be used for combining different tool sets for removing car-window edge strips and dried glue attached with the edge strips with convenience and quickness.

1. Field of the Invention
This invention relates to a removing tool for car-window edge strips, particularly to one convenient to use, possible to use different tool sets changeable, and quickly removing edge strips in the outer side of a car window.
2. Description of the Prior Art
Generally a car window is provided with an edge strip closely contacting the glass of the car window for preventing water from directly flowing into the door and also scraping off water drops off the glass in case of the glass is lowered down. However, dirt and water may accumulate in the gap between the edge strip and the glass over time, resulting in erosion and breakup of the edge strip after a certain period of use. Therefore, the edge strip sometimes has to be replaced with new one. At present, no special tools for removing the car-window edge strip, and a flat tool such as a flat-tip screwdriver is usually used for removing it. As the edge strip is closely contacting the glass, a worker without a time-tested experience may not be dexterous enough to do the work and hurt in plying off edge strips or harm the metal portion of a window. Even if edge strips are pried off, there remains dried glue in the edge, necessary to be taken off by a knife, resulting in potential cut in a worker's fingers or hand.

Removing tool for car-window edge strips


Provided are systems and methods for simplifying cloud compute markets. A compute marketplace can be configured to determine, automatically, attributes and/or constraints associated with a job without requiring the consumer to provide them. The compute marketplace provides a clearing house for excess compute resources which can be offered privately or publically. The compute environment can be further configured to optimize job completion across multiple providers with different execution formats, and can also factor operating expense of the compute environment into the optimization. The compute marketplace can also be configured to monitor jobs and/or individual job partitions while their execution is in progress. The compute marketplace can be configured to dynamically redistribute jobs/job partitions across providers when, for example, cycle pricing changes during execution, providers fail to meet defined constraints, excess capacity becomes available, compute capacity becomes unavailable, among other options.

Cloud computing developed from the need of private companies to recover their investment in compute grids by renting out spare cycles in off-peak times. Typical implementations in compute grids infrastructure often resulted in over-provisioned compute grids and spare cycles of compute power that were not being utilized. As the market for cloud compute resources has been established, more dedicated providers have emerged in commercial settings, such as Amazon EC2, Softlayer, and Rackspace to provide excess compute capacity to consumers. Others have specifically developed compute grids to offer such processing power to consumers both on an as needed basis and on a subscriptions based model. The development of compute marketplaces and the increase in the number of compute provides has limited some of the waste associated with excess compute capacity. However, even these dedicated providers also suffer from the need to over-provision physical resources to insure sufficient compute capacity for a given job at any given time.
As the market for cloud services has grown, providers have pushed to differentiate themselves based on price, reliability, manageability, platform and other factors and features. Typically consumers of cloud compute services, however, are not interested in these complexities. Consumers are often most concerned with getting their compute work done "as soon as possible," "as cheaply as possible," or within some time or price constraint. Thus, the identification of underlying capacities of given cloud compute systems overwhelms the typical consumer.

Method and apparatus for clearing cloud compute demand


An EnodeB or a transmitting device intermittently generates synchronization signals, and then performs perfect omnidirectional pre-coding processing on the synchronization signals; the synchronization signals after perfect omnidirectional pre-coding processing pass through a transmission channel and are then received by a mobile terminal or a receiving device, and the mobile terminal or the receiving device uses the received synchronization signals and local replicas of the synchronization signals for receiving and synchronization processing. An EnodeB or a transmitting device generates vector signals via low-dimensional space-time coding, and then performs perfect omnidirectional pre-coding processing on the vector signals; the transmitted signals after perfect omnidirectional pre-coding processing pass through a transmission channel and are then received by a mobile terminal or a receiving device, and the mobile terminal or the receiving device uses the received signals for signal receiving processing.

In recent years, a MIMO (large-scale MIMO) wireless communication system with an EnodeB configured with a large number of antennas has gained wide attentions from the academia and the industry. In the large-scale MIMO system, the EnodeB is generally configured with more than ten antenna units (such as 128 or 256), and serves for dozens of users (such as 40) in the meanwhile. A large number of antenna units of the EnodeB can greatly increase the degree of spatial freedom of wireless communication, greatly improve the transmission rate, spectrum efficiency and power efficiency, and eliminate the interference between cells to a large extent. The increase of the number of antennas makes each antenna unit be made in a smaller size with a lower cost. Using the degree of spatial freedom provided by the large-scale antenna units, the EnodeB of each cell can communicate with many users in the cell on the same time-frequency resource at the same time, thus greatly increasing the spectrum efficiency. A large number of antenna units of the EnodeB also enable each user to have better spatial directivity for uplink and downlink transmission, so that the transmitting power of the EnodeB and a mobile terminal is obviously reduced, and the power efficiency is greatly increased. When the antenna number of the EnodeB is sufficiently large, random channels between each user and the EnodeB can approach to be orthogonal, and the interference between the cell and the users and the effect of noises can be eliminated. The plurality of advantages described above enable the large-scale MIMO to have a magnificent application prospect.
A public channel has a very important effect in a cellular system, and much information of the EnodeB needs to be delivered to the users through the public channel, such as synchronization signals, cell reference signals, control signaling, multimedia broadcast multicast services (MBMS), etc. One basic requirement on the design of the public channel is that the signal transmitted has an omnidirectional property, so as to guarantee reliable coverage. The existing omnidirectional transmitting methods (such as single antenna transmission, cyclic delay diversity (CDD) and space-time block coding (STBC)) are only applied to a MIMO system with few transmitting antennas (no more than eight), and these methods cannot be directly applied to the large-scale MIMO system configured with large-scale array antennas. For example, a traditional method is that a single omnidirectional antenna is used to broadcast signals (one antenna can be selected from a plurality of transmitting antennas for transmitting); however, the selected single antenna has to be equipped with a power amplifier larger and more expensive than other antennas, so as to achieve the same power coverage scope under the condition that all the antennas are used. Since one of the key advantages of the large-scale MIMO is to obviously increase the power efficiency, i.e., the power amplifier configured to each antenna unit can be obviously reduced with the quantity increase of the antennas, it can be seen that, if the single antenna transmission method is directly used in large-scale MIMO, the advantage of the expected power efficiency will be lost. The space-time coding transmission and the cyclic delay diversity (CDD) are omnidirectional diversity transmission technologies widely used in LTE and other systems which not only have difficulty in system design, but also have an application bottleneck problem that pilot overheads are linearly increased with the antenna number of the EnodeB if these two methods are directly expanded and applied in the large-scale MIMO system. In recent years, spatial domain signal expansion or pre-coding methods have been proposed regarding the omnidirectional signal transmission problems in the large-scale MIMO system, but none of these methods can guarantee perfect omnidirectional transmission. The different signal transmitting powers in each spatial direction will affect the synchronization performance and the omnidirectional signal transmission performance to a large extent.

Methods for sending and receiving synchronization signals and signals subjected to perfect omnidirectional pre-coding in large-scale MIMO system