This invention provides a method and a kit for rapid and robust development monoclonal antibodies. The method does not require hybrid technologies nor does it require single cell manipulations. The method allows elimination of cross-target antibodies.

Development of monoclonal antibodies that can be recombinantly produced in mammalian cell cultures has high priority goal in research and medical areas. The crucial step in this process is determination the sequences of antigen binding domains of antibodies with desired properties. Many different techniques are described for this but these techniques also have shortcomings related to time-consumption, cost or efficiency of sequence production. For these reason there is a need for a robust, rapid, inexpensive and flexible method for development of monoclonal antibodies suitable for production in mammalian cell factories.
Generally, monoclonal antibodies (MAbs) are made by identical immune cells and they have monovalent or monospecific affinity: they bind to the same epitope. However, there are antibodies, which are produced by completely different, non-identical immune cells, which bind to the same epitope. The high affinity and selective binding of MAbs to their antigens make them highly potent for use in biochemistry, molecular biology and medicine.
Historically, the first method for isolation of monoclonal antibodies was hybridoma technology. This technology is based on forming hybrid cell lines (hybridomas) by fusion of antibody-producing B cell with a myeloma cell. The antibodies produced by the particular hybridoma clone are all of a single specificity. Thus, single clones are screened for identification of antibody with desired properties. However, the production of the MAbs by hybridoma technology has also some shortcomings: the process needs relatively long time (up to several months) and has complications if applied to organisms other than murine species. Moreover, no antibody sequence information becomes directly available by the method. Thus, when the hybridoma screened antibody is selected for further development (e.g. for developing therapeutic products), the variable domains of heavy (VH) and light chain (VL) that together determine antibody's antigen binding properties must be isolated from the hybridoma cells and sequenced. Sequence data is ultimately needed for recombinant production of the final MAb product as well as for improvements, such as humanization, isotype conversion, affinity maturation etc.
In contrast, recombinant antibody isolation technologies usually do not include hybrid cell line step but involve obtaining of VH and VL domain sequences from antibody expressing source cells (e.g. B-cells from spleen, bone marrow or blood). Commonly, VH and VL cDNAs are amplified by RT-PCR using mRNA isolated from the cells. By combinatory library based strategies large repertoire of different VH and VL sequences are amplified from population of cells (e.g. millions of B-cells isolated from immunized animal). Thereafter, the amplified products are used for construction of combinatory libraries by random pairing of VH and VL domains. Thus, combinatory strategies necessarily involve the screening step for identification of the antibodies (VH and VL combinations) with desired properties from large libraries. These screening methods involve in vitro antibody display techniques, such as phage display and ribosome display, as well as in vivo display platforms, such as bacterial, yeast, and recently also mammalian cell-surface displays. Mammalian cell display has a number of features which are advantageous for selecting antibodies for recombinant production. For example, using mammalian cells for screening ensures that later there will be no loss of activity of MAb when the antibody is produced as natural post-translationally modified IgG molecule in mammalian cells. Loss of activity is a complication sometimes associated with MAbs screened in phage, bacterial and even yeast display systems. Instead, performing the screening in mammalian cells ensures that recovered active antibody is synthesized, modified, assembled and secreted through the authentic mammalian cellular pathways.
The recombinant methods also include non-combinatorial strategies that are based on retrieving of antibody sequences from single B-cell or clonally expanded progeny of the single cell. By this way the original heavy and light chain pairs are kept together during the development process. This can be achieved by amplification of re-arranged VH and VL region cDNAs from one particular B-cell by a technically challenging single-cell RT-PCR based methods. Also the isolated single B-cells can be amplified in cell culture. The methods include immortalization of the differentiated B-cells, e.g. using Epstein-Barr virus (EBV), retroviral oncogenes, TLR ligands, or cultivation in specific conditions with irradiated thymoma cells or using IL4 treatment and CD40 triggering. In addition, techniques are developed for facilitating or increasing the efficiency of the non-combinatorial strategies, e.g. by enrichment of source B-cells that express the antibodies with desired affinity. For example lymphocyte capturing (panning) has been used on the antigen coated surface for establishment of retained B-cell cultures that were used as source of VH and VL sequences. Microwell array chip assay or fluorescence based sorting methods have been used for identification and isolation of cells secreting antibodies with desired properties. However, all of the non-combinatory methods involve either complicated single-cell manipulations and/or establishment of sterile primary cell cultures from biological materials, specialized equipment and expensive supplements.
The methods, and the kit described here below provide solutions to the shortcomings of the currently existing technologies.

Method for development of monoclonal antibodies


A memory hub module includes a decoder that receives memory requests determines a memory request identifier associated with each memory request. A packet memory receives memory request identifiers and stores the memory request identifiers. A packet tracker receives remote memory responses and associates each remote memory response with a memory request identifier and removes the memory request identifier from the packet memory. A multiplexor receives remote memory responses and local memory responses. The multiplexor selects an output responsive to a control signal. Arbitration control logic is coupled to the multiplexor and the packet memory and develops the control signal to select a memory response for output.

Computer systems use memory devices, such as dynamic random access memory ("DRAM") devices, to store data that are accessed by a processor. These memory devices are normally used as system memory in a computer system. In a typical computer system, the processor communicates with the system memory through a processor bus and a memory controller. The processor issues a memory request, which includes a memory command, such as a read command, and an address designating the location from which data or instructions are to be read. The memory controller uses the command and address to generate appropriate command signals as well as row and column addresses, which are applied to the system memory. In response to the commands and addresses, data are transferred between the system memory and the processor. The memory controller is often part of a system controller, which also includes bus bridge circuitry for coupling the processor bus to an expansion bus, such as a PCI bus.
Although the operating speed of memory devices has continuously increased, this increase in operating speed has not kept pace with increases in the operating speed of processors. Even slower has been the increase in operating speed of memory controllers coupling processors to memory devices. The relatively slow speed of memory controllers and memory devices limits the data bandwidth between the processor and the memory devices.
In addition to the limited bandwidth between processors and memory devices, the performance of computer systems is also limited by latency problems that increase the time required to read data from system memory devices. More specifically, when a memory device read command is coupled to a system memory device, such as a synchronous DRAM ("SDRAM") device, the read data are output from the SDRAM device only after a delay of several clock periods. Therefore, although SDRAM devices can synchronously output burst data at a high data rate; the delay in initially providing the data can significantly slow the operating speed of a computer system using such SDRAM devices.
One approach to alleviating the memory latency problem is to use multiple memory devices coupled to the processor through a memory hub. In a memory hub architecture, a memory hub controller is coupled over a high speed data link to several memory modules. Typically, the memory modules are coupled in a point-to-point or daisy chain architecture such that the memory modules are connected one to another in series. Thus, the memory hub controller is coupled to a first memory module over a first high speed data link, with the first memory module connected to a second memory module through a second high speed data link, and the second memory module coupled to a third memory module through a third high speed data link, and so on in a daisy chain fashion.
Each memory module includes a memory hub that is coupled to the corresponding high speed data links and a number of memory devices on the module, with the memory hubs efficiently routing memory requests and memory responses between the controller and the memory devices over the high speed data links. Each memory requests typically includes a memory command specifying the type of memory access (e.g., a read or a write) called for by the request, a memory address specifying a memory location that is to be accessed, and, in the case of a write memory request, write data. The memory request also normally includes information identifying the memory module that is being accessed, but this can be accomplished by mapping different addresses to different memory modules. A memory response is typically provided only for a read memory request, and typically includes read data as well as an identifying header that allows the memory hub controller to identify the memory request corresponding to the memory response. However, it should be understood that memory requests and memory responses having other characteristics may be used. In any case, in the following description, memory requests issued by the memory hub controller propagate downstream from one memory hub to another, while memory responses propagate upstream from one memory hub to another until reaching the memory hub controller. Computer systems employing this architecture can have a higher bandwidth because a processor can access one memory device while another memory device is responding to a prior memory access. For example, the processor can output write data to one of the memory devices in the system while another memory device in the system is preparing to provide read data to the processor. Moreover, this architecture also provides for easy expansion of the system memory without concern for degradation in signal quality as more memory modules are added, such as occurs in conventional multi drop bus architectures.
Although computer systems using memory hubs may provide superior performance, they nevertheless may often fail to operate at optimum speeds for a variety of reasons. For example, even though memory hubs can provide computer systems with a greater memory bandwidth, they still suffer from latency problems of the type described above. More specifically, although the processor may communicate with one memory device while another memory device is preparing to transfer data, it is sometimes necessary to receive data from one memory device before the data from another memory device can be used. In the event data must be received from one memory device before data received from another memory device can be used, the latency problem continues to slow the operating speed of such computer systems.
Another factor that can reduce the speed of memory transfers in a memory hub system is the transferring of read data upstream (i.e., back to the memory hub controller) over the high-speed links from one hub to another. Each hub must determine whether to send local responses first or to forward responses from downstream memory hubs first, and the way in which this is done affects the actual latency of a specific response, and more so, the overall latency of the system memory. This determination may be referred to as arbitration, with each hub arbitrating between local requests and upstream data transfers.
There is a need for a system and method for arbitrating data transfers in a system memory having a memory hub architecture to lower the latency of the system memory.

System and method for arbitration of memory responses in a hub-based memory system


An information recording method for recording content information in a recording medium having at least re-readable area, comprising converting, based on a first conversion rule φ1, first information including a first component for obtaining content control information, converting, based on a second conversion rule φ2, second information including a second component for obtaining the first information, and writing the converted first information and the converted second information into the re-recordable area of the recording medium.

1. Field of the Invention
The present invention relates to a method and an apparatus for recording information including secret information, effective for recording a content necessitating protection of copyright and a method and an apparatus for reproduction thereof.
2. Description of the Related Art
Recently, any type of information can be digitized and technology capable of distributing such information through transmission media or recording media has been developed, as expressed by the term "digital revolution." As a result, a great number of people have come to acquire digital information freely. In such an environment, signals such as digital audio signals, digital video signals, relating data which computers handle are recorded in a recording medium. Information transmission and storage are carried out so that the above-described signals are reproduced from the recording medium, information is copied to a read-only medium, transmitted information is reproduced or information is transmitted through a transmission line.
Recently, as a recording medium capable of recording a large volume of video/audio information, the digital versatile disc (DVD) has been realized. A movie over two hours long is recorded in a DVD and such DVD recorded information is reproduced through a playback apparatus, so that the movie can be watched freely at home.
DVDs are classified into: read-only DVD-ROMs, DVD-Rs which allow a one-time recording, and DVD-RW, DVD-RAM which allow re-recording.
DVD-video is a standard currently used which allows a whole movie to be recorded in a single disc. A user can acquire information based on digital signals freely through reproduction of such DVD-video discs or reception of digital broadcasting. Under such circumstances, if the acquired digital signals are copied to a recording medium such as a hard disc and the aforementioned DVD-RAM and encoded with an encoder based on the DVD-video standard, it is possible to copy a disc.
Thus, in a DVD-video, digital information to be recorded is encrypted. The copy protect method employing cryptography technology functions effectively for a DVD-video disc or DVD-ROM, in which encrypted information is pre-recorded.
In the field of such information transmission and storage processing, recently, copyright protection is gaining in importance. Particularly, if information necessitating protection of copyright is recorded on an ordinary recording medium, illegal copy needs to be prevented. That is, although an individual having a copyright permits recording of information to only a single recording medium, it is possible to illegally copy the information onto a number of recording medium, thus preventing this is of the utmost importance.
Because a rewritable or re-recordable recording medium has appeared, generation control information is needed for the content, and its control information includes "copy is prohibited," "a single copy is permitted," "copying several times is permitted" and the like.
Recently, as a concept for content control, such concepts as "move," "check-out," and "check-in" have appeared. These words are defined as follows.    (1) "Move": Moving the content from a recording area to another recording area. Consequently, the content written into an original recording area is erased.    (2) "Check-out": Copy is permitted N times or the content is copied from a recording area (or first recording medium) to another recording area (or second recording medium). The content written into an original recording area is not erased but copy control information N is reduced by one. Of course, if N=0 is reached, the content cannot be copied any more. Although usually, a copied content can be reproduced, this copied content is not permitted to be copied further.    (3) "Check-in": When the copy control information of the content in an original recording area is for example, (N−1) times, executing processing for returning that content from the other recording area recorded previously. As a result, the copy control information for controlling the content of the original recording area is increased by one, i.e., changed to N times. It follows that the content written into the other recording area is erased.
If an information recording/reproducing apparatus, which operates according to one of the above concepts is used faithfully to its function, there occurs no problem. However, the information recording/reproducing portion may be modified so that the copy control information is made meaningless. Thus, the presence of the copy control information becomes meaningless.
Technologies for blocking such illegal copy of digital signals are disclosed in Japanese Patent KOKAI Publications No. 9-128990, No. 8-204584, and No. 8-28684.
The Japanese Patent KOKAI Publication No. 9-128990 discloses a method of recording by replacing a part of an error correction code with specific information (encryption key or the like). According to this method, since a part of the digital data or the error correction code is replaced with the specific information, an error occurs in the replaced portion. Therefore, if the amount of the specific information increases, the error rate of the original data increases, which increases the load on error correction processing.
According to Japanese Patent KOKAI Publication No. 8-204584, when supplying data subjected to error correction processing to a decoding portion, a correction impossible data portion is replaced with a special code containing a synchronous code so that it can be detected by the decoding portion. The decoding portion recognizes the error portion using the special code to carry out decoding.
According to the Japanese Patent KOKAI Publication No. 8-286840, encryption is carried out by changing additional information or the position of the additional information in order to prevent illegal copying. The allocation structure of digital data is determined so as not to occur a correction impossible state of digital data due to a data error generated by embedding encryption key information.
To control the content and control information (including copy control information), encryption and decryption processing is carried out for the content and control information in the information recording/reproducing portion. However, key information for encrypting or decrypting the content or control information may be illegally removed. Consequently, decrypting of the content and control information is enabled, so that it is possible that the content is duplicated illegally into another recording medium or recording area in a large quantity and the content is decrypted.
In order to prevent such illegal copying, procedures for encryption and decryption need to be improved further. Additionally, the recording medium for recording the content or key information and the recording/reproduction method must also be improved.

Method and apparatus for recording information including secret information and method and apparatus for reproduction thereof


A cutting machine having a rotatingly driven cutting tool (2) and a tool guard (1). The tool guard (1) has a first tool guard part (11) which is fixedly mounted with respect to the apparatus and a second tool guard part (12) which can be pivotably mounted relative to the first tool guard part (11). Each tool guard part includes side walls (30, 32) lying adjacent to respective sides of the cutting tool and a center web which connects the two side walls to each other. The center web (31) extends curved in the peripheral direction and is disposed above the cutting tool (2). In order to perform a disturbance-free pendular cut, the pivotable second tool guard part (12) carries a slide piece (40) which projects beyond the end edge (34) of the center web (31) and has a rounded outer slide surface (35) facing away from the center web (31). The end edge (34) faces away from the fixed first tool guard part (11).

In work apparatus of the kind mentioned above, such as cutting machines, a vacuum fan is mounted on the tool guard. The tool guard has a first tool guard part which is stationary and a second tool guard part which is pivotally mounted. The vacuum fan is mounted on the stationary tool guard part and is driven together with the cutting disc by a drive motor. The pivotable tool guard part has a center web having an end edge. This end edge rests upon the workpiece to be cut in order to ensure that the abrasion dust, which occurs during the cutting operation is taken up and vacuum removed as completely as possible.
When cutting in the forward direction, the forces acting on the end edge effect a pivoting of the second tool guard part into the stationary first tool guard part without significantly affecting the guidance of the work apparatus. When cutting in the opposite direction, the forces acting on the end edge of the center web lying on the workpiece cause the work apparatus to stand up whereby the guiding reliability is affected. This can lead even to lifting the cutting disk out of the kerf which, under some circumstances, can require the work apparatus to be positioned once again for cutting and this often leads to a ragged cut edge. For rough workpiece surfaces, problems in guiding the work apparatus therefore occur with a back and forth cutting movement (pendular cut).

Portable hand-guided work apparatus having a tool guard


A combined audio and electrical anatomy-signal sensor which is designed to collect, essentially from a selected, common anatomical site, related audio and electrical anatomical signals, such as heart-produced signals. The sensor includes a unique body structure which is designed to function both as a part of the audio-information gathering structure, and as a part of electrical electrode structure for gathering electrical signals. Chamber space is provided within this body for receiving and containing desired electrical circuitry, in the form of circuit-board-supported electrical components, which may be designed to perform any one of a number of different functions relative to signal gathering and transferring at and from an anatomical site. The presence of such circuitry within the body of the proposed sensor enables use of the sensor for specialized signal gathering and processing purposes, under circumstances which can obviate the need for various, special retro-modifications of existing, external, signal-monitoring apparatus.

The present invention relates to a combined audio and electrical signal sensor, or collector, for gathering anatomical signals. For the purpose of illustration herein, a preferred embodiment of the invention, and certain modifications thereof, are described in conjunction with collecting heart-produced signals, such as heart-produced sound and ECG signals, with respect to which application the invention has been found to offer particular utility. While the description which follows below is specifically presented in the setting of collecting such heart-related signals, it should be understood that the combined collection of these specific kinds of signals is intended to represent, more generally, the collection of various kinds of related anatomical audio and electrical signals.
Those involved in the field of cardiology recognize that there are circumstances wherein it is useful, and important, to collect simultaneously produced heart-related audio and ECG signals, and most preferably to collect such signals, as nearly as is possible, from a common anatomical site. The present invention addresses this situation by proposing a unique, integrated, audio/electrical signal sensor which (a) is specially designed to perform simultaneous collection, effectively from a selected, common anatomical site, of these two kinds of signals, and (b) includes within it selected electrical circuitry (circuit components) which function to play a selectable, predetermined role regarding either the manner(s) in which signals are collected preparatory to outward delivery to external apparatus, such as to external cardio-monitoring apparatus, or the manner(s) in which collected signals may be processed before such delivery, or both.
Proposed in accordance with this invention is a signal-collection sensor which is specially designed in a manner that uniquely enables body structure, or the body, in the sensor to play roles in the collections of both kinds of signals (audio and electrical) from a common anatomical site. In the preferred and best-mode form, or embodiment, of the invention, the sensor body is a unitary structure, and in an alternative embodiment, it is a plural-part (two-part) structure. The sensor body, as proposed by the present invention, has an anatomy-facing side which is shaped with an outwardly facing, concave, acoustic dome which defines a cavity for the gathering of audio signals. Preferably, this cavity takes the form of a volume of revolution which is centered symmetrically with respect to what is called herein a signal-collection symmetry axis that is intended to intersect a selected anatomical site when the sensor is placed on the anatomy for use. It is especially the presence of this acoustic cavity which enables the sensor body to play an important role in acoustic signal gathering. With the sensor in use in a condition with the mentioned signal-collection axis intersecting a selected anatomical site, sounds gathered in the cavity, which is thus substantially symmetrically disposed relative to that site, can be considered to be "coming from" the site per se.
The sensor body is also formed with electrical conductor structure, whereby this body effectively acts as an ECG-signal-collecting electrode. In the preferred embodiment of the invention, the sensor body is made of an electrically conductive plastic material. In an alternative embodiment, the sensor body is integrated with an appropriate electrically conductive surface coating. When the sensor is positioned on the anatomy for use, the anatomy-facing side of the body, and particularly that portion of the anatomy-facing side which circumsurrounds the acoustic cavity, is generally symmetrically disposed relative to the particular, selected anatomical site, whereby collected electrical signals can also be treated as coming essentially from the selected anatomical site per se.
Space is provided within a chamber region formed inside the sensor body for the presence of selected electrical circuitry, including electrical circuit components which, as suggested earlier, may play a role in defining the manners in which audio and electrical signals are gathered and are delivered to the "outside world".
These and other features and advantages that are offered by the invention will become more fully apparent as the description which now follows is read in conjunction with the accompanying drawings.

Combined electrical and audio anatomical signal sensor


The subject matter disclosed herein is generally directed to methods and compositions for tagging cells of interest, tracking evolution of the tagged cells, and recovering the original tagged cells for further study. Specifically, cells are tagged with a DNA construct encoding a barcode sequence comprising a guide sequence. Barcoded cells can then be recovered using a reporter construct having CRISPR target sequences specific for the cell having a barcode of interest.

Elucidating the biological processes underlying evolutionary selection is fundamental to our understanding of the genesis of human disease and its response to therapy. However, a comprehensive analysis of both the phenotypic and genomic underpinnings of evolutionary fitness has been precluded by the high cost, extensive labor and cell destructive nature of single-cell phenotypic and genetic characterization methods.
Tracking sub-clones and their progeny ("lineages") within a population of cells is essential to understanding the dynamics of evolutionary selection. Diverse libraries of inert DNA barcodes have provided a scalable methodology for tracking individual cells, but preclude phenotypic and genetic characterization of the drivers of evolutionary dynamics. Single-cell characterization methods have facilitated characterization, but are challenging to scale appropriately due to their high cost, inability to preserve cell viability, reduced resolution and incompatibility with current barcoding strategies. Moreover, studying the lineages that are not selected for is impossible using current methods. As a result, the determinants of drug sensitivity, clonal non-selection and unfit epigenetic states are precluded from discovery and the ability to capitalize on them is blunted. Thus, a bottleneck in defining the genetic and phenotypic basis of evolutionary selection is the lack of an experimental system that permits tracking, selection, and viable recovery at any stage of evolution of cells from specific lineages, permitting phenotypic and genomic characterization of these cells and their progeny. A novel methodology is crucial to move from passive population-level observations of cancer evolution to testing clone specific, mechanistic hypotheses.

Methods and compositions for studying cell evolution


New humanized and chimeric monoclonal antibodies that recognize EGF-R and comprise an artificial sequence at least of the FRs of the heavy chain variable region of a human immunoglobulin. The hypervariable regions of both monoclonal antibodies is the following amino acid sequence: light chain:. CDR-1: arg-ser-ser-gln-asn-ile-val-his-ser-asn-gly-asn-thr-tyr-leu-asp; PA1 CDR-2: lys-val-ser-asn-arg-phe-ser; PA1 CDR-3: phe-gln-tyr-ser-hys-val-pro-trp-thr. PA1 CDR-1: asn-tyr-tyr-ile-tyr; PA1 CDR-2: gly-ile-asn-pro-thr-ser-gly-gly-ser-asn-phe-asn-glu-lys-phe-lys-thr; PA1 CDR-3: gln-gly-leu-trp-phe-asp-ser-asp-gly-arg-gly-phe-asp-phe.. Heavy chain:. Use of the antibodies for therapeutical and diagnostic purposes.

The Epidermal Growth Factor (EGF), which is a 53 amino acid polypeptide with a molecular weight of 6045 D, was isolated and purified for the first time from murine submaxillary gland (Cohen S; J Biol Chem (1962) 237, 1555). Later, a similar molecule was obtained from human urine (Cohen S and Carpenter G; (1975) PNAS USA 72, 1317). The action of this polypeptide is mainly performed via its membrane receptor, a 170 KD molecular weight glycoprotein. Its intracellular domain is associated with a tyrosine kinase activity with structural homology to the oncogene v-erb-B showing relation to the malignant transformation process (Heldin C H et al; (1984) Cell 37, 9-20).
High levels of EGF-R have been detected in malignant tumors originating in the epithelium such as breast, bladder, ovarian, vulva, colonic, lung, brain and esophagus cancers. The role played by EGF and its receptor in regulating tumor growth is unknown, but it has been suggested that the EGF-R expression in tumor cells provides a mechanism for autocrine growth stimulation which leads to uncontrolled proliferation (Schlessinger J, Schreiber A B, Levi A, Liberman T and Yarden Y; (1983) Crit Rev Biochem 14(2), 93-111).
It has been reported that EGF produces overgrowth of breast cancer cell lines (Osborne C K et al; (1980) Cancer Research 40, 2361), besides that it modulates the differentiation under some cellular systems (Tonelli C J; Nature (1980) 285, 250-252). These effects on cellular differentiation and proliferation are related to the high expression of EGF-R (Buss J E et al; (1982) PNAS 79, 2574).
The presence of EGF-R in tumor cells has proven to be an indication of a poor prognosis in human breast cancer. Approximately 40% of the breast tumors show specific binding sites of high affinity for the EGF (Perez R, Pascual M R, Macias A, Lage A; (1984) Breast Cancer Research and Treat 4, 189-193). There is also an inverse correlation with the presence of estrogen receptor, indicating EGF-R as an indifferentiation marker or an indicator of the potential capacity of proliferation of the malignant cells.
Other groups have reported that the expression of EGF-R is higher in regional ganglionar metastasis than in primary carcinomas of breast (Sainsbury J R et al; (1985) Lancet 1, 8425, 364-366) and that the expression of the receptor is different in the different histologic subtypes of human breast carcinoma cells, their presence constituting a signal of bad prognosis (Macias A et al; Anti Cancer Research 6: 849-852).
The evidences obtained in different studies have prompted to consider the EGF/EGF-R system as a possible target for therapeutic actions.
We obtained a murine monoclonal antibody (R3), raised against the human placenta as described in European Patent application No. 93202428.4, and found to bind to the external domain of the human EGF-R. It was found to inhibit the binding of EGF at both low and high affinity EGF-R sites.
Passive immunotherapy using monoclonal antibodies against the EGF-R have been the object of multiple investigations, which have demonstrated that the specific recognition of the receptor by the antibody inhibits the EGF binding, with an inhibitory effect on the mitogenic stimulation of malignant cells (Sato J D et al; (1987) Methods in Enzimology 148, 63-81); but there is evidence that the murine origin of these antibodies produces a human anti-mouse antibody response.
The development of the hybridoma antibody technique by Kohler and Milstein revolutionized the discipline of immunochemistry and provided a new family of reagents with potential applications in clinical diagnosis and immunotherapy (Kohler G, Milstein C; (1975) Nature 256, 495-497). While it has become routine to produce mouse monoclonal antibodies (mAbs) for use in basic research and clinical diagnosis, it has been difficult to use these for in vivo immunotherapy because they have reduced half-life in humans, poor recognition of mouse antibodies effector domains by the human immune system and the foreign immunoglobulin can elicit an antiglobulin response (HAMA response) that may interfere with therapy.
The ability to genetically manipulate antibody genes and then to express these altered genes by transfection techniques enables us to produce mAbs having more desirable properties than the existing hybridoma antibodies. Thus genetic engineering can be used to enhance desired effector functions in antibody molecules and to decrease or eliminate undesired effector functions.
The use of recombinant DNA technology to clone antibody genes has provided an alternative whereby a murine mAb can be converted to a predominantly human form with the same antigen binding properties. S L Morrison in 1984 created mouse-human antibody molecules of defined antigen-binding specificity by taking the variable regions genes of mouse antibody producing myeloma cell lines and joining them to human immunoglobulin constant region (Morrison S L et al; (1984) PNAS USA 81, 6851-6855).
Other authors have attempted to build rodent antigen binding sites directly into human antibodies by transplanting only the antigen binding site, rather than the entire variable domain, from a murine antibody (Jones P T et al; (1986) Nature 321, 522-524; Verhoeven M et al; (1988) Science 239, 1534-1536). Some applications of this method have been developed (Rietchmann L et al; (1988) Nature 332, 323-327; Quee C et al; (1989) PNAS USA 86, 10029-10033), other authors have worked with reshaped antibodies, which included some murine residues in human FRs in order to recover the affinity for the original antigen (Tempest PR; (1991) Biotechnology 9, 266-272).
Orlandi R et al (Proc Natl Acad Sci USA 86, 3833-3837, 1989) disclose the constant regions of the human gamma-1 heavy chain and the human kappa light chain, and suitable cloning vectors therefor.

Humanized and chimeric monoclonal antibodies that recognize epidermal growth factor receptor (EGF-R); diagnostic and therapeutic use


A printer includes an idler movement mechanism that rotates a transfix member at a speed corresponding to a rotational speed for a rotating image member before moving the transfix member into engagement with the rotating image member to form a nip. The printer includes a rotating image member for receiving colorant from a print head to form an image on the rotating image member, a motor having rotational output that is coupled to the rotating image member for rotating the rotating image member at a first surface speed, a transfix member for forming a nip with the intermediate print member to transfer the image from the intermediate print member to media in the nip, the transfix member being moveable from a first position, in which the transfix member does not form a nip with the intermediate print member, to a second position, in which the transfix member forms the nip with the intermediate print member, and a rotational transfer link for coupling the transfix member in the first position to the rotation of the rotating image member so the transfix member rotates at a second surface speed that corresponds with the first surface speed as the transfix member is moved to the second position to form the nip with the rotating image member rotating at the first surface speed.

Modern printers use a variety of inks to generate images from data. These inks may include liquid ink, dry ink, also know as toner, and solid ink. So-called "solid ink" refers to ink that is loaded into a printer as a solid, which is typically in stick or pellet form. The solid ink is melted within the printer to produce liquid ink that is supplied to a print head for ejection onto media or an intermediate member to generate a printed image from image data. These solid ink printers typically provide more vibrant color images than toner or liquid ink jet printers.
A schematic diagram for a typical solid ink imaging device is illustrated in FIG. 1. The solid ink imaging device, hereafter simply referred to as a printer 100 has an ink loader 110 that receives and stages solid ink sticks. The ink loader 100 has a plurality of feed channels in which the ink sticks are placed. Typically, a feed channel is provided for each color of ink used in the printer. For example, a color printing machine has a feed channel for each of the black, cyan, yellow, and magenta colors that are used for color printing.
The ink sticks progress through a feed channel of the loader 110 until they reach an ink melt unit 120. The ink melt unit 120 heats the portion of an ink stick impinging on the ink melt unit 120 to a temperature at which the ink stick melts. The liquefied ink is supplied to one or more print heads 130 by gravity, pump action, or both. Printer controller 180 uses the image data to be reproduced to control the print heads 130 and eject ink onto a rotating print drum 140 as image pixels for a printed image. Media 170, such as paper or other recording substrates, are fed from a sheet feeder 160 to a position where the image on the drum 140 can be transferred to the media. To facilitate the image transfer process, a pressure roller 150, sometimes called a transfix or transfer member, presses the media 170 against the print drum 140. Offset printing refers to a process, such as the one just described, of generating an ink or toner image on an intermediate member and then transferring the image onto some recording media or another member.
In some offset printing processes, the intermediate member is brought to a stop so the transfix member can be brought into contact with the intermediate member to form a nip. The leading edge of the media is then fed into the nip as the intermediate member is driven to commence rotation of the member. The rotation of the intermediate member also drives the free-wheeling transfix member so the two rotating members push the media through the nip for the transfer of the image from the intermediate member to the media. While stopping the rotation of the intermediate member facilitates the coordination of the media and transfix member with the intermediate member, it reduces the number of images that can be generated by the printer. Consequently, offset printing processes have been developed that continue to rotate the intermediate member while coordinating the movement of the media and transfix member with the intermediate member.
While these offset printing processes increase printing productivity, they also introduce additional mechanical stresses to the transfer process. One issue is related to the movement of a stationary transfix member into engagement with the rotating intermediate member. The inertial load of the stationary transfix member requires a brief period of time for the intermediate member to bring the transfix member up to the appropriate speed for transfer of the image. Additionally, some slippage between the two members may occur as the rotating intermediate member imparts its driving force to the transfix member. The impact of the stationary transfix member on the rotating intermediate member also puts some stress on the motor driving the intermediate member. Responding to the repetitive load of the stationary transfix member being applied to the intermediate member over the long term may reduce the operational life of the motor.

Mechanism for transfix member with idle movement


Use of a disposable filtration capsule with a non-occluded membrane filter element in the place of a standard spiral wound cartridge allows for the more rapid and quantitative filtration, recovery, and quantitation of microorganisms in liquid, particularly surface waters, well water, tap water, and the like. The capsule allows a severe reduction in the water sample size tested, substantially minimizes risks of cross-contamination, and provides a leak-proof vessel for shipment. Risk of infection of laboratory personnel and time of analysis are both reduced. Costs of measuring contamination by microorganisms such as Giardia and Cryptosporidium is lowered significantly while increasing the accuracy and dependability of the measurement.

Protection of the sanitary nature of drinking water is a concern worldwide. While numerous sources of microbial contamination exist, a principle concern is the introduction of pathogenic intestinal protozoa such as Cryptosporidium and Giardia into the water supply. These microorganisms are particularly troublesome, as they are often present in the form of cysts and oocysts. The process of encystment renders the organisms environmentally resistant. Such intestinal pathogens are often introduced into the environment by the direct deposit of human or animal feces (both domestic and feral), or through purposeful or accidental discharge of sewage or wastewater into the lake, stream, or aquifer which supplies raw water to be treated for the purpose of rendering it potable. In addition to testing the drinking water for the presence of microorganisms, tests upstream can often identify the source of contamination. In addition to drinking water tests, tests of water where swimming or bathing is expected is also often necessary to prevent spread of disease, as is illustrated by the closure of much of the Western shore of Michigan's Lake Saint Clair during the summer of 1993 due to fecal contamination from sewage overflow and concurrent weather conditions which maintained rather than ameliorated the contamination in windward areas.
The current proposed test for Cryptosporidium and Giardia is set forth in ASTM D-19 Proposal P229, "Proposed Test Method for Giardia Cysts and Cryptosporidium Oocysts in Low-Turbidity Water by a Fluorescent Antibody Procedure." The proposed test method of the Environmental Protection Agency (EPA), United States, was published in 59 FED. REGISTER No. 28, 6416-6427 (Feb. 10, 1994), and is substantially similar to the ASTM P229 method. Both methods are herein incorporated by reference.
In the ASTM P229 method, water to be tested is directed through a cartridge filter containing a spiral wound 25.4 cm (10 inch) long depth filter. The recommended water volume is 380 L (100 gallons), and is directed through the filter cartridge, the nominal 1 .mu.m spiral wound filter element retaining suspended matter (but see below) and passing the water in which the sediment is suspended. When the necessary quantity of water has traversed the filter, the cartridge is disassembled, and the water present in the cartridge housing and the cartridge itself are transferred to a plastic sample bag, e.g., a Zip-Lock.RTM. bag, and preferably double bagged, for transportation to the laboratory.
In the lab, the filter cartridge is cut apart with a knife or scalpel and the yarn wrapping and sediment separated into three portions, an interior, relatively sediment-free portion, an intermediate portion, and an outside, heavily sedimented portion. The yarn in each of these portions is washed successively with the same three 1.0 L volumes of eluting solution, the most interior yarn being washed first. The washing step consists of massaging the yarn in the eluting solutions by hand, or alternatively adding the yarn to a stomaching bag (alternative EPA procedure) and homogenizing in a stomacher followed by hand massaging and homogenizing a second time.
The eluate, containing sediment and any microorganisms trapped by the filter, is centrifuged for 10 minutes at 1050.times. g in 250 ml centrifuge bottles in a swinging bucket centrifuge, the supernatant discarded to waste and the solids combined, resuspended, and n recentrifuged to produce a pellet whose volume is measured, a portion of which is resuspended and tested for the presence of Cryptosporidium and Giardia by standard molecular methods, in this case fluorescent antibody procedures. Additional information relative to these molecular methods as well as other methods which may, in general, be useful is disclosed by Abdallah M. Isa, "Elisa Technology", ENCYCLOPEDIA OF MICROBIOLOGY, Vol. 2, pp. 59-62 (1992); J. Lederberg, Ed., "Indirect Fluorescent Antibody Tests and Other Immunomicroscopic Methods", ENCYCLOPEDIA OF MICROBIOLOGY, Vol. 2, pp. 163-164 (1992); E. Baron, L. Peterson and S. Finegold, DIAGNOSTIC MICROBIOLOGY, Bailey & Scott's; pp. 1015-1085; D. Jones, "Polymerase Chain Reaction (PCR)", ENCYCLOPEDIA OP MICROBIOLOGY, Vol. 3, pp. 443-449 (1992); and J. Conroy, R. Stevens and K. Hechemy, "Enzyme Immunoassay", ENCYCLOPEDIA OF MICROBIOLOGY, Vol. 3, pp. 87-92 (1992) which are incorporated by reference.
The prior art methods of testing leave much to be desired. Among the deficiencies are the following:
Filter cartridges and housings from different manufacturers are not fully inter-changeable; PA1 Filter cartridges may be installed incorrectly; PA1 Filter housings must be cleaned thoroughly between uses, which is both time-consuming as well as offering the potential for cross-contamination; PA1 Filter "pore size," although nominally 1 .mu.m, spans a wide range, allowing considerable sediment and microorganisms, if present, to pass through; PA1 Housing water and filter cartridge are stored in plastic bags which are susceptible to leakage through damage or improper closure, presenting both cross-contamination, transportation, and loss of sample risks; PA1 Installation and removal must be performed with protective equipment (latex gloves). PA1 The filter element must be manually cut-apart with a knife or scalpel, which poses a risk of infection to the technician, even when wearing latex gloves; PA1 The washing procedure is laborious and uses a large quantity of eluate; PA1 The washing procedure is inefficient, resulting in relatively low recovery of microorganisms, and in addition is highly variable; PA1 The centrifugation of eluate requires large centrifuge bottles which are preferably discarded after use to avoid cross-contamination; and PA1 The combination of centrifuged samples for further concentration runs the risk of sample loss and/or contamination.
The foregoing deficiencies are associated with the basic nature of the filter cartridge and housing and its use in the field. However, upon arrival at the laboratory, further serious deficiencies arise. For example:
The foregoing are but some of the deficiencies associated with the prior art process. As an indication of how much of an impact these deficiencies may have on microorganism quantitation, in a round robin test in which water containing a known quantity of challenge microorganisms was "quantitated" using the proposed ASTM procedure, an average of less than 3% (EPA Contract No. 68-C3-0365, WA No. 2-2, p. 21) of cryptosporidium microorganisms were recovered.
It would be desirable to provide a method of isolation of microorganisms from liquids which minimizes the potential for contamination and cross-contamination; which substantially prevents leakage during shipment; which maximizes sediment and microorganism retention; which is more economical of time and capital; which substantially decreases risk of infection of laboratory personnel; which allows quantitation with smaller sample size; which may provide smaller quantities of eluate with which to work; and which provides the opportunity for greater accuracy and reliability of the quantitation.

Filtration device for quantitation of microorganism contaminated liquids


Systems and methods which provide organization of content using robust content information to enable presenting content to a user organized in a highly relevant way are disclosed. According to embodiments, a user does not control the organization of the particular content (although the user may establish some level of preferences), but rather content organization rules may be autonomously applied through analysis of robust content information and provide content organized in a thematic organizational structure which is highly relevant to the user. Such content organization rules may identify content connection points which are not readily apparent, but which nevertheless provide a collection of content which is relevant. Such content organization rules may operate to provide organization of content related through a thematic thread, such as may comprise a temporal aspect, a geographic aspect, a subject matter aspect, a content file aspect, a setting aspect, a general aspect, and/or the like.

With the proliferation of consumer electronics, such as personal computers having document generation and media content capabilities, digital video recorders, digital cameras, digital recorders, and smart devices having image and/or sound recording features readily available to capture various content, and personal digital media players and smart devices having image and/or sound reproduction features almost omnipresent to provide playback of the various content, the instances of digital media content created by and available to users is quite large. A user may, for example, generate and store numbers of digital documents, photographs, videos, sound files, etc.
Unfortunately, however, the organizational techniques employed for storing and thus later accessing such digital media content tends to be manual and relatively simplistic. For example, a user may employ a simple hierarchical folder or directory (collectively referred to herein as folders) structure in which various digital media content is associated only through their inclusion in a same folder. The level of organizational granularity provided with respect to such folders is typically not detailed (e.g., "my trip to Europe", "work documents", "videos", etc.). Implementing a fine level of granularity for content organizational structure using such folders is often not practical, requiring significant time to navigate the hierarchical folders and to manually sort the content. Moreover, such organizational structures are static, leaving the content in the folders, and thus associated with the other content of the particular folder, unless and until the user takes steps to manually reorganize the folders.
Accordingly, the use of such digital media content is often not fulfilling and generally diminishes with time. For example, the time required to access content of interest is sometimes impractical, and even more so with the passage of time. With the stagnant nature of the content and its organization, the user often loses interest in the content as time goes on. Moreover, the lack of spontaneity in current data and media retrieval technologies produces a barrier to entry for personal content enjoyment for the end-user.
Various data aggregators have been developed to deliver external content (e.g., content from sources other than the user and the user's devices), such as commercially produced news and information. Such data aggregators merely provide external content based upon key words, phrases, and other search criteria established by the user or on the user's behalf. The content aggregated by the data aggregators is not associated with the user's own digital media content and does nothing to improve or otherwise supplement the user's experience with respect to their own digital media content.

Systems and methods for organizing content using content organization rules and robust content information


A system provides mechanisms and techniques to retrieve trace data from a trace buffer residing in a data storage system. The software program operating on a processor within the data storage system operates in trace mode to produce trace data in the trace buffer upon occurrence of trace events. An event trace routine operates in response to a system call to access the trace buffer and return either a current value of a trace buffer pointer or the current trace buffer pointer as well as trace data read from the trace buffer beginning at a location and in an amount as specified in the system call to the event trace routine. The trace capture process can operate either within the data storage system or preferably on a remote host computer system to access trace data in the trace buffer in the data storage system by using the event trace routine. The trace capture process can periodically query the event trace routine with a frequency determined by an adaptive timing algorithm in order to detect the addition of trace data to the trace buffer. Upon detecting such a condition, the trace capture process can use the event trace routine to retrieve the trace data from the trace buffer. The trace capture process can also detect if trace data is written beyond the end of the trace buffer and can perform the proper sequence of trace data access operations using the event trace routine in order to provide continuous remote access to all trace data produced in the trace buffer.

Most types of computer systems have a requirement to maintain data for prolonged periods of time. To meet this requirement, a typical computer system includes a coupling to a data storage system which the computer system can access to store and retrieve the data. The computer system may be coupled to the data storage system via a high speed data transfer interface (e.g., a small computer system interface (SCSI), a Fibre-Channel interface (e.g., ESCON), or the like), or the coupling may be formed over a computer network such as a Storage Area Network (SAN) that may link a plurality of computer systems to one or more high-capacity data storage systems. Through an interoperation of software (e.g., applications, operating systems, protocols and the like) and hardware (e.g., circuitry) in both the computer system and the data storage system, the computer system is able to access data within storage media (e.g., disk drives) that the data storage system controls.
Within a typical data storage system, one or more processors (e.g., Central Processing Units or CPUs) operate according to prescribed software program(s) to manage and control access to the data within the storage media in the data storage system on behalf of the computer systems that request access to such data. Such data storage system software programs are generally considered the operating system or control program for the data storage system. For example, within a high-capacity data storage system such as one of the Symmetrix line of data storage systems manufactured by EMC Corporation of Hopkinton, Mass., U.S.A., a front end interface provides a coupling for the data storage system to one or more computer system(s) (via direct interfaces or via a SAN) while a back end interface provides a coupling to the storage media devices (e.g., disk drives) within the data storage system that stores data. The front and back end interfaces are coupled by a data bus (one or more) which allows the interfaces to interoperate with each other. A cache memory system is accessible on the data bus for use by the front and back end interfaces to temporarily store data during processing. A processor operating within the front end interface (e.g., on a circuit board that operates as the front end interface) operates a software program (e.g., firmware or microcode) that performs high speed processing of data (and requests for such data) between the front end interface and the remotely connected computer systems. Likewise, the back end interface includes a processor that operates a software program to handle tasks associated with accessing (e.g., reading and writing) data to and from the storage devices within the data storage system based on the requests received by the front end interface.
Due to the complex operation of a typical data storage system, the software programs which perform (e.g., execute or otherwise operate) on processor(s) such as the front and back end interfaces within a data storage system can become quite large and complex. By way of example, the microcode software program which provides the access request processing operations for a front end interface within a Symmetrix data storage system may be many thousands of lines of code in length. During the design, development and testing of such complex data storage system software control programs, software developers frequently include the ability for the software program to operate in a "trace mode" which allows the program to trace the occurrence of certain trace events during the program's operation. Essentially, trace mode operation causes the software program to capture trace data as defined by a software developer in relation to an occurrence of the certain defined or selected trace events.
Before operating a software program in trace mode in a conventional data storage system, a software developer is able to define one or more trace events and associated trace data which is to be captured upon occurrence of each trace event. The software developer can then operate the software program in trace mode. While operating in trace mode, the software program in the data storage system is able to detect occurrences of each trace event during operation of the software program. Upon detection of a trace event, the software program performs or calls a designated trace routine (which is itself generally considered part of the software control program) which is responsible for capturing trace data (e.g., variable or data structure values, data access request formats, command parameters, and so forth) related to the trace event. The trace routine places the trace data, which may include the current values of data structures, parameters, input/output request values, and so forth that are relevant to the trace event as designated by the software developer, within a trace buffer in the cache memory system within the data storage system. The trace buffer is typically a reserved area of the cache memory system which is limited in size, for example, to sixteen or thirty-two megabytes (MB).
After the software developer operates the software program in trace mode for a certain period of time in order to exercise the features of the program which would typically cause the trace event(s) to occur, the software developer can halt the operation of the software program. At this point, the trace buffer in the cache memory system contains the trace data which the trace routines captured during operation of the software program at the occurrence of each trace event. The software developer can then view the trace data within the trace buffer in the cache memory system by interaction, for instance, with a service processor (e.g., a keyboard and monitor) which is integrated as part of the data storage system. By reviewing the trace data, the software developer can determine if the software program for which the trace data was generated had properly performed in the data storage system during its operation.
Some data storage system configurations include a service processor that allows the software developer to download the trace data from the trace buffer onto a removable storage medium such as a floppy disk so that the trace data can be transported to another computer system for further analysis. By viewing the trace data according to these techniques, the software developer can debug the software program to determine whether or not it is operating properly.

Methods and apparatus for accessing trace data


The present invention relates to novel formulations comprising a sprayable composition comprising tranexamic acid and chitosan for use in the treatment of wounds or injuries, in particular for use as a topical hemostatic composition or for surgical intervention and the process for preparation thereof.

The use of hemostatic agents provides for control of bleeding in surgical procedures.
WO01/28603 relates to an injectable formulation for delivery of a composition comprising an osteogenic protein and a hemostatic gelatin foam paste as well as to a method of making a hemostatic gelatin foam paste suitable for injecting osteogenic protein, the method comprising hydration of Gelfoam® powder with glutamic acid buffer.
U.S. Pat. No. 5,394,886 relates to a skin biopsy plug wherein the plug is a porous sponge made from gelatin material, which is implanted into a wound, swells, absorbs blood, and is completely absorbed in the patient. It relates to a combination of the punch (the blade for excising skin) and the plug. The plug used is the commercially available Gelfoam®.
Gelfoam® is a commercially available product providing powdered gelatin for application on to bleeding surfaces as a hemostatic agent. The powdered gelatin is provided in a full glass jar with a metal lid or in a sachet, each of which are to be opened and the contents of which, i.e. the gelatin, are to be poured into a sterile beaker or bowl.
U.S. Pat. No. 5,645,849 claims a hemostatic patch comprising a biodegradable gelatin matrix, a hemostatic-promoting amount of thrombin and epsilon aminocaproic acid.
JP62221357 discloses a skin ointment for promoting a hemostatic effect comprising thermoplastic resin or rubber dissolved in solvent and contains dispersed gelatin powder. The product is an ointment comprising thermoplastic resin or rubber and a fine powder of collagen, gelatin or chitosan.
FR2679772 relates to particulate material to create an embolism comprising a polymer coated with a hemostatic or thrombotic agent. The hemostatic agent may be a finely divided gelatin powder.
U.S. Pat. No. 6,096,309 relates to a hemostatic composition comprising thrombin and a mixture of non-microfibrillar collagen and microfibrillar collagen in an aqueous medium wherein the microfibrillar collagen has an average fibril diameter of about 3-30 nm.
U.S. Pat. No. 4,515,637 relates to both a method of forming a collagen-thrombin hemostatic composition and to a lyophilized collagen product, comprising collagen and thrombin.
U.S. Pat. No. 6,045,570 relates to a gelatin powder for use as a hemostatic agent and to a biological sealant comprising a gelatin slurry which includes milled gelatin powder. The slurry preferably comprises Gelfoam® powder mixed with a diluent selected from saline and water. The slurry demonstrates superior flow characteristics in that it exhibits minimal latency and can be easily injected or introduced through catheter lumens, especially small lumens. The product therefore has very fluid characteristics.
U.S. Pat. No. 8,722,081 discloses the hemostatic textile material to stop bleeding, it consists of tranexamic acid, dialdehyde cellulose carrier, blood coagulation factor and bacteriolytic agent. Tranexamic acid is an antifibrinolytic agent that competitively inhibits the activation of plasminogen to plasmin. Tranexamic acid is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin, i.e., actions similar to aminocaproic acid. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid. Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. Tranexamic acid competitively inhibits activation of plasminogen (via binding to the kringle domain), thereby reducing conversion of plasminogen to plasmin (fibrinolysin), an enzyme that degrades fibrin clots, fibrinogen, and other plasma proteins, including the procoagulant factors V and VIII. Tranexamic acid also directly inhibits plasmin activity, but higher doses are required than are needed to reduce plasmin formation.
US2003/0012741 relates to a process for preparing micronized collagen. It is stated that the particle size should not exceed 20 μm in order to optimize adhesion to the wound surface.
US2015/0038406 relates to a pharmaceutical composition of tranexamic acid and also consists of antibiotic, aesthetic agent, NSAID and excipient or carrier that facilitates local administration.
US2016/0310615 relates to a spray composition comprising a co-block polymer coupled with a water soluble polymer, and a polymer delivery solvent.
Various hemostatic spray for control of bleeding from wounds are commercially available as Traumacel S® a hemostatic dusting powder in a pressurized spray, the active component being a hydrogen calcium salt of oxidized cellulose; Traumacel P® a powdered hemostatic agent comprising a calcium salt of oxidized cellulose (carboxymethylcellulose calcium) which is applied as dry powder onto a bleeding area; Avitene® is a microfibullar collagen hemostat "flour" typically applied dry and Arista® is a hemostatic spray based on microporous polysaccharide hemospheres as described in U.S. Pat. No. 6,060,461 relating to particles, in particular dextran particles, having a particle size from 0.5-1000 μm and an average pore diameter from 0.5-1000 nm. It is disclosed that such particles may be used for enhancing clot formation on a wound by administering the particles in the form of a dry powder.
Katharine Ker et al, Cochrane Database Syst Rev. 2013 Jul. 23; (7): (Topical application of tranexamic acid for the reduction of bleeding) discloses the effects of the topical administration of tranexamic acid in the control of bleeding.
Jim Bartley et al, Med Hypotheses. 2013 December; 81(6):1036-8: (Should chitosan and tranexamic acid be combined for improved hemostasis after sinus surgery) discloses the chitosan combined with a hemostatic agent such tranexamic acid as well as improving hemostatic control should lead to improved clinical outcomes after endoscopic sinus surgery, however this document does not disclose the amount of chitosan and tranexamic acid concentration used for improving hemostatic control after endoscopic sinus surgery.
Hemostatic control is also a part of total knee arthroplasty. Total knee arthroplasty is a major surgical procedure, which is carried out with tourniquent, causing major blood loss in post-operative period due to dramatically increased perfusion in the limb and enhanced fibrinolysis.
Chaitanya Krishna et al, International Journal of Orthopaedics Sciences 2016; 2(2): 01-04: (Topical and intravenous tranexamic acid in reducing blood loss in total knee arthroplasty? A comparative study in Indian population) discloses that topical tranexamic acid and intravenous tranexamic acid are equally efficacious and its recommended for use of tranexamic acid for reduction of peri- and post-operative blood loss in Total knee arthroplasty patients. The topical tranexamic acid reduces the systemic side effects, and topical tranexamic acid in one group is given as tranexamic acid 2 gm in the intra-articular drain and drain was clamped for one hour and then opened to retained the tranexamic acid in the joint space.
Abdel et al, J Bone Joint Surg Am. 2018; 100:1023-9; (Intravenous Versus Topical Tranexamic Acid in Total Knee Arthroplasty) discloses that both intravenous and topical tranexamic acid were effective in reducing calculated blood loss and transfusion rates in patients undergoing elective total knee arthroplasty. The topical tranexamic acid used in this study is 3 gm of tranexamic acid diluted in 45 mL of normal saline solution (total volume of 75 mL) and topically applied after cementation.
However, there exists a need to develop the pharmaceutical composition of spray for treating wounds or injuries, in particular for use as a topical hemostatic composition or for surgical intervention. The present invention relates more specifically to a topical spray composition comprising tranexamic acid and chitosan.

Tranexamic acid spray for knee arthroplasty


A method and apparatus for allowing a television viewer to quickly and easily relate the teams' names and scores to the players are disclosed. The teams' names and scores are presented on a small scoreboard or banner on the television screen, and either the backgrounds of the names and scores or the names and scores themselves are colored the same color as the selected uniform portions of the respective teams. This can also be applied to presentations of statistics.

1. Field of the Invention
This invention relates to televised sporting events.
2. Related Art
Televised sporting events usually have a small scoreboard displayed on the television screen showing the name of each team or an abbreviation thereof, the score of each team, the quarter, period, or inning of the game, and the time left in the quarter or period, if applicable. In these scoreboards, each team's name and score, and the backgrounds for the names and scores, are the same color. The technology currently exists to choose the color for the display of the teams' names and scores, or background colors of the names and scores. However, in the prior art there is no relationship between the color of the teams' names and scores, or the background colors, and the teams' colors. Further, in the prior art, the same color is used for both teams' name and score, and the background for both is the same color.
It can be difficult for a viewer to relate the name and score of a team to the players on the field. This is due in part to the fact that many fans do not know each team's colors. The large number of teams in play makes it difficult to identify a team until a close-up camera displays a team name or logo.
Similarly, televised sporting events sometimes have a banner across the top or bottom of the television screen displaying the name and score of each team. Again, it can be difficult for a viewer to determine which players belong to which team, and hence, which team on the field is currently winning the game.
Televised sporting events also show statistics for each team, or for players from each team playing corresponding positions, or for other comparative purposes. Again, it can be difficult for a viewer to determine which team players belong to, making it difficult to determine which team has achieved the statistics shown.

Televised scoreboard or statistics presentation with colors corresponding to players' uniforms


A method for printing solder paste onto a surface of a printed circuit board through the medium of a screen having openings. The method includes feeding the paste into a chamber of a dispenser, dispensing the paste contained in the chamber onto a first side of the screen and onto the surface of the board from the dispenser through a slit-like aperture, removing paste residue from the first side of the screen by a blade extending from a first cleaning apparatus, removing paste residue from a second side of the screen by another blade extending from a second cleaning apparatus, and sucking and transporting the paste residue adhered to inner peripheral surfaces of openings in the screen as well as the paste residue being removed from the second side of the screen by a vacuum device connected to the second cleaning apparatus. The slit-like aperture of the dispenser is formed by a fixed front wall and a moveable rear wall selectively moving toward and away from the fixed front wall.

1. Field of the Invention
The present invention relates generally to a method for dispensing viscous materials, and more particularly to a method for screen printing of solder paste onto a surface of a printed circuit board through the medium of a screen having a plurality of openings that is used in producing surface mount technology circuit boards.
2. Description of the Prior Art
There are various methods by which solder paste can be printed on a printed circuit board. One approach is to use the screen printing apparatus which has a spatula-like squeegee which is arranged to be displaced back and forth along a pair of parallel-oriented guide rails and is arranged to be raised and lowered relative to the guide rails. This screen printing apparatus is adapted to be in pressure contact with an upper surface of the screen when it is lowered and placed into a lower position where solder paste is printed onto a surface of a printed circuit board through the medium of the screen. This type of screen printing apparatus is disclosed in the Japanese Patent Gazette No. 1-55597 published on Nov. 27, 1989. In this type of screen printing apparatus, a considerable amount of solder paste is manually supplied onto the screen prior to operating the apparatus and the solder paste supplied onto the screen in such a way is printed on the surface of the circuit board by reciprocating the squeegee, while its lower end is pressed against the screen to introduce the solder paste into openings in the screen. Another screen printing apparatus similar to the above-mentioned type of apparatus is also disclosed in the Japanese Patent Gazette No. 1-19275 published on Apr. 11, 1989.
Major disadvantages of this type of screen printing apparatus are that as a considerable amount of solder paste placed on the screen is kept exposed to the air until the apparatus is put into operation, it tends to be solidified due to evaporation of flux contained therein and/or to be oxidized as it contains oxidizable components, such as lead. As the printing of solder paste is performed by reciprocating the squeegee, the solder paste tends to be excessively printed on a surface of the circuit board. As a result, printed films tends to be blurred on the surface of the circuit board and, in addition, a uniform printing effect cannot be obtained in every printing cycle. It is difficult to prevent the solder paste from acquiring of such changes as solidification, oxidation, etc., even if it is frequently kneaded on the screen with manual labour during the period when the apparatus is not in operation. To use such a solidified and/or oxidized solder paste brings about undesirable printing effect. For this reason, it must be removed from the screen and replaced with new solder paste. This means that a considerable amount of solder paste becomes a useless waste to be abandoned. In addition, replacement of solder paste not only requires the manual labour, but also requires printing operation to be stopped for a certain period of time. This results in an economic loss and worker exposure to lead which is a health concern.
A screen printing apparatus which is provided with an apparatus for cleaning solder paste residue from a lower surface of a screen having a plurality of openings therein is also already known. This type of apparatus is also disclosed in the Japanese Patent Gazette No. 1-19275 referred to above and is characterized by the provision of a paper-wrapped roller as a means for cleaning solder paste residue from the lower surface of the screen. The paper-wrapped roller is arranged to be reciprocated in a rolling engagement with the lower surface along a pair of guide rods in order to wipe off the residue adhered to the lower surface of the screen. A major disadvantage of this type of apparatus is that the paper-wrapped roller can only clean the residue from the lower surface and cannot clean the residue adhered to inner peripheral edges of the openings of the screen.


A process of forming a compound film includes formulating a nano-powder material with a controlled overall composition and including particles of one solid solution. The nano-powder material is deposited on a substrate to form a layer on the substrate, and the layer is reacted in at least one suitable atmosphere to form the compound film. The compound film may be used in fabrication of a radiation detector or solar cell.

Solar cells convert sunlight directly into electricity. These electronic devices are commonly fabricated on silicon (Si) wafers. However, the cost of electricity generated using silicon-based solar cells is rather high, compared to electricity generated by the traditional methods, such as fossil-fuel-burning power plants. To make solar cells more economically viable, low-cost, thin-film growth techniques that can deposit high-quality light-absorbing semiconductor materials need to be developed. These techniques need to employ cost-effective approaches to grow solar cell absorbers on large-area substrates with high throughput and high materials utilization. Therefore, low-cost and high-efficiency thin film solar cell fabrication requires: i) a solar cell absorber material that fundamentally has the capability to yield high-efficiency devices, ii) a low-cost deposition technique that can deposit this absorber material in the form of a high-quality thin film on a low-cost substrate. Both of these ingredients are necessary for manufacturing high-efficiency, low-cost solar cell structures. When solar cells formed on large-area substrates are interconnected, modules with higher voltage and power output are obtained.
Copper-indium-gallium-sulfo-selenide, Cu(In,Ga)(S,Se)2, compounds are excellent absorber materials for thin-film solar cell structures provided that their structural and electronic properties are good. An important compositional parameter of Cu(In,Ga)(S,Se)2 thin films is the metals molar ratio of Cu/(In+Ga). The typically acceptable range of this molar ratio for high-efficiency solar cell absorbers is about 0.70–1.0, although in some cases when the compound is doped with a dopant such as sodium (Na), potassium (K) or lithium (Li), this ratio can go even lower. If the Cu/(In+Ga) molar ratio exceeds 1.0, however, a low-resistivity copper selenide, sulfide or sulfo-selenide phase precipitates and deteriorates the performance of the device due to electrical shorting paths it creates through the absorber. Therefore, control of the Cu/(In+Ga) ratio is important for any technique that is used for the preparation of Cu(In,Ga)(S,Se)2 films for radiation detector or solar cell applications. The Ga/(In+Ga) ratio is also important to control since this ratio determines the bandgap of the absorber, which can be varied from about 1 eV (for CuInSe2) to 2.43 eV (for CuGaS2). In principal the Ga/(In+Ga) ratio may vary from zero in CuIn(S,Se)2 to 1.0 in CuGa(S,Se)2. However, laboratory experience to date has shown that best device efficiencies are obtained for Ga/(In+Ga) ratios in the range of 0.1–0.3.
Although important to control, the Cu/(In+Ga) and Ga/(In+Ga) ratios are not the only factors that influence the electronic properties of Cu(In,Ga)(S,Se)2 compound thin films. The compositional ratios of a compound film may be within the acceptable ranges, but solar cells fabricated on this film may still have poor light-to-electricity conversion efficiencies. Cu(In,Ga)(S,Se)2 compound thin films used in high-efficiency solar cell structures, besides having the right composition, also need to have good morphology and large-grain structure. For example, a typical high-quality Cu(In,Ga)(S,Se)2 thin film is 1.0–3.0 μm thick; it is dense and it has columnar grains with widths of at least 0.5 μm.
One approach that yielded high-quality Cu(In,Ga)Se2 films for solar cell applications is co-evaporation of Cu, In, Ga and Se onto heated substrates in a vacuum chamber [see for example, Bloss et al., "Thin Film Solar Cells", Progress in Photovoltaics, 1995, vol. 3, page 3]. Absorbers grown by this technique are typically dense and they have large columnar grains. The Cu/(In+Ga) ratio and the Ga/(In+Ga) ratio are closely controlled during deposition by monitoring and controlling the individual evaporation rates of Cu, In and Ga. Consequently, Cu(In,Ga)Se2 solar cells fabricated on co-evaporated absorbers yielded small, laboratory-size solar cells with close to 19% conversion efficiency. Although there are now concentrated efforts to apply this technique to the fabrication of large-area Cu(In,Ga)Se2 modules, the method is not readily adaptable to low-cost production of large-area films, mainly because control of Cu/(In+Ga) and Ga/(In+Ga) ratios by evaporation over large-area substrates is difficult, materials utilization is low and the cost of vacuum equipment is high.
Another technique for growing Cu(In,Ga)(S,Se)2 type compound thin films for solar cell applications is the two-stage processes where at least two components of the compound are first deposited onto a substrate, and then reacted with each other and/or with a reactive atmosphere in a high-temperature annealing process. U.S. Pat. No. 4,798,660 issued to J. Ermer et al. teaches a method for fabricating a CuInSe2 film comprising sequentially depositing a film of Cu on a substrate by DC magnetron sputtering and depositing In on said film of Cu and heating the composite film in the presence of Se to form the compound. This approach is schematically depicted in FIG. 1, as it would be applied to the growth of a Cu(In,Ga)Se2 thin film. In FIG. 1, a Cu sub-layer 12 is first deposited on a substrate 10 which has a metallic film 11, such as molybdenum (Mo) on its surface. Then a (In+Ga) sub-layer 13 is deposited over the Cu sub-layer 12 to form the composite layer 14. Later in the process, the complete structure of FIG. 1 is heated in the presence of Se vapors to convert the composite layer 14 into a Cu(In,Ga)Se2 compound layer.
Karg et al. in U.S. Pat. No. 5,578,503 teach an alternate two-stage technique where a Cu film, an In or Ga film and a S or Se film are deposited on a substrate to form a stacked layer and then this stacked layer is heated rapidly to form the compound. The stacked structure of this prior art approach is depicted in FIG. 2, as it would be applied to the growth of a Cu(In,Ga)Se2 solar cell absorber. In FIG. 2, a Cu sub-layer 22 is first deposited over the metal film 21 which is previously coated on substrate 20. This is followed by the depositions of a (In+Ga) sub-layer 23 and a Se sub-layer 24. All the sub-layers form the stacked layer 25 which is then converted into a Cu(In,Ga)Se2 compound layer when the whole structure of FIG. 2 is rapidly heated in a rapid thermal processing (RTP) furnace.
Yet another two-stage processing approach is taught in European Patent application No EP0838864A2 by K. Kushiya et al. In that method a stacked precursor comprising a Cu—Ga sub-layer and an In sub-layer was employed. This method is schematically shown in FIG. 3 as it would be applied to the growth of a Cu(In,Ga)Se2 absorber. According to FIG. 3, a Cu—Ga sub-layer 32 is first deposited over the metal contact layer 31 which was previously deposited on the surface of substrate 30. An In sub-layer 33 is then deposited over the Cu—Ga sub-layer 32. The structure of FIG. 3 is then annealed in the presence of Se vapors to convert the multi-layer 34 into a Cu(In,Ga)Se2 layer. Further annealing in H2S yields a Cu(In,Ga)(S,Se)2 film.
All of the prior art two-stage techniques reviewed above yielded high-quality compound films in terms of their structural and electronic properties. Large-scale manufacturing, however, also requires strict control of the material composition over large-area substrates. This means that in the two-stage processes that utilize a stack of various sub-layers, the uniformity and thickness of each sub-layer have to be individually controlled over large-area substrates. This is very difficult. DC magnetron sputtering techniques which are commonly used to deposit the sub-layers of FIGS. 1, 2 and 3 are expensive vacuum techniques with low materials utilization. Therefore, their cost is high.
Since compositional control, especially the control of the Cu/(In+Ga) ratio is important for Cu(In,Ga)(S,Se)2 compounds, attempts have been made to fix this ratio in an initial material, before the deposition process, and then transfer this fixed composition into a thin film formed using this initial material. T. Arita et al. in their 1988 publication [20th IEEE PV Specialists Conference, 1988, page 1650] described a screen printing technique that involved mixing and milling pure Cu, In and Se powders in the compositional ratio of 1:1:2 and forming a screen printable paste, screen printing the paste on a substrate, and sintering this film to form the compound layer. They reported that although they had started with elemental Cu, In and Se powders, after the milling step the paste contained the CuInSe2 phase. Solar cells fabricated on the sintered layers had very low efficiencies because the structural and electronic quality of these absorbers were poor.
Thin layers of CuInSe2 deposited by a screen printing method were also reported by A. Vervaet et al. [9th European Communities PV Solar Energy Conference, 1989, page 480]. In that work a CulnSe2 powder was used along with Se powder to prepare a screen printable paste. Layers formed by screen printing were sintered at high temperature. A difficulty in this approach was finding a suitable fluxing agent for dense CulnSe2 film formation. Therefore, solar cells fabricated on the resulting layers had poor conversion efficiencies.
U.S. Pat. No. 5,985,691 issued to B. M. Basol et al describes another particle-based method to form a Group IB-IIIA-VIA compound film, where IB=Cu, Ag, Au, IIIA=In, Ga, Al, Tl, and VIA=S, Se, Te. The described method includes the steps of preparing a source material, depositing the source material on a base to form a precursor, and heating the precursor to form a film. In that invention the source material includes Group IB-IIIA alloy-containing particles having at least one Group IB-IIIA alloy phase, with Group IB-IIIA alloys constituting greater than about 50 molar percent of the Group IB elements and greater than about 50 molar percent of the Group IIIA elements in the source material. The powder is milled to reduce its particle size and then used in the preparation of an ink which is deposited on the substrate in the form of a precursor layer. The precursor layer is then exposed to an atmosphere containing Group VIA vapors at elevated temperatures to convert the film into the compound. The precursor films deposited using this technique were porous and they yielded porous CuInSe2 layers with small-grain regions as reported by G. Norsworthy et al. [Solar Energy Materials and Solar Cells, 2000, vol. 60, page 127]. Porous solar cell absorbers yield unstable devices because of the large internal surface area within the device. Also small grains limit the conversion efficiency of solar cells.
PCT application No. WO 99/17889 (Apr. 15, 1999) by C. Eberspacher et al. describes methods for forming solar cell materials from particulates where various approaches of making the particulates of various chemical compositions and depositing them on substrates are discussed.
As the above brief review of prior art demonstrates, there have been attempts to use Cu(In,Ga)Se2 compound powders, oxide containing particles, and Cu—(In,Ga) alloy powders with (In,Ga)-rich compositions, to form precursor layers which were then treated at high temperatures to form Cu(In,Ga)Se2 compound films. These techniques were successful in demonstrating compositional control. In other words the overall composition of the powder was directly transferred into the precursor layer and then into the compound layer. As discussed previously however, composition is only one of the important parameters of high-quality solar cell absorbers. The other important parameters are the morphology and the grain size, which directly influence the electronic properties of these films. Solar cell absorbers need to be dense layers with large grain size. This requires precursor layers that are dense and compositionally uniform both in micro-scale and macro-scale. Repeatability and the overall yield of the process further requires the quality of the source material or the initial powder material to be repeatable. This means that the chemical composition and the phase content of the individual particles comprising the powder need to be well controlled and repeatable.
To this end, there is a need for a low-cost method that has the capability to form Cu(In,Ga)(S,Se)2 thin films over large-area substrates with controlled compositional uniformity, good structural and electronic properties in a repeatable manner with high yield.

Method of forming semiconductor compound film for fabrication of electronic device and film produced by same


A blocking apparatus for positioning in front of a person's face, the apparatus in certain aspects having a front member disposable in front of a person's face, the front member having two spaced-apart ends, two tab members, each tab member projecting from one of the two spaced-apart ends of the front member, each tab member disposable at an angle to the front member and each tab member permanently attachable to another item or, in certain aspects, the front member releasably attachable to another item, and the front member sized and shaped for blocking, e.g. snow, rain, moisture and/or light on a portion of a person's face and/or eyes.

1. Field of the Invention
This invention is directed to apparatus for selectively blocking light, moisture, glare and/or sunlight in a person's vision field, on a person's face and/or on a person's eyes.
2. Description of Related Art
The prior art discloses a wide variety of sunshades, headgear, headbands, hats, eyeshades, visors, and caps.
There has long been a need for apparatus that effectively partially blocks part of a person's field of vision. There has long been a need for an apparatus to block light, etc. on a person's eyes.


A compact optoelectronic module that prevents undesirable heating by locating the electrical drive and/or receiving (control) circuit outside of the housing containing the optoelectronic transducer. The control circuit is mounted on a submount (PCB). The housing is mounted on the submount adjacent to the control circuit, and the optoelectronic transducer is coupled to the control circuit via a mount (leadframe) that extends substantially perpendicular to the submount plane and is surface mounted on the submount. The housing includes an opening, and a lens is provided between the optoelectronic transducer and the opening and defines an optical axis that is parallel to the submount plane. An encapsulating body is used to secure the optoelectronic transducer and mount inside the housing, and a portion of the encapsulating material is used to form the lens.

DE 199 09 242 A1 discloses an optoelectronic module in which a mount with an optoelectronic transducer is positioned in a module housing and is encapsulated by means of a translucent material which can be shaped. The light is injected or output via an optical fiber, which is coupled to a connecting stub on the module housing. The driver module and the receiving module for the optoelectronic transducer are also located on the mount.
The data rates for POF transmission systems are rising increasingly. So-called RCLEDs (Resonant Cavity LEDs) with data rates of up to 500 Mbit/s are thus being used increasingly. These RCLEDs have the disadvantage that they have a resonant-like behavior in the temperature range from about −40° C. to 85° C. In particular, there is a considerable reduction in power at the upper temperature limit. These reductions in power can be decreased by circuitry measures on the driver module.
In the case of transceiver embodiments in which the driver module is encapsulated in the encapsulation body with the RCLED, it is, however, impossible to implement appropriate circuitry measures. Firstly, it is difficult to additionally accommodate the external circuitry in the encapsulation body and to carry out the wiring. Secondly, a large amount of heat is developed, because the driver stage and the optical transmission source draw more current at high data rates, and because of the additional external circuitry. This heating can lead to clouding or blackening of the encapsulation body, and to destruction of the transducer module.
The only known way until now to reduce undesirable heating has been to restrict the temperature range to 0° C. to about 60° C. External circuitry which reduces the reductions in the power of the transducer module are also dispensed within the case of transducer modules which are encapsulated in an encapsulation body. Obviously, this is not satisfactory.
U.S. Pat. No. 5,768,456 describes an optoelectronic module having a transmitting and/or receiving element which is arranged on a flexible substrate. The flexible substrate is connected to a printed circuit board. A holding is provided for holding an optical waveguide which can be coupled to the transmitting and/or receiving element, and the holder is likewise arranged on the printed circuit board.
U.S. Pat. No. 5,259,052 discloses an optical plug arrangement, in which an optical plug has a protective bracket which can be moved in the longitudinal direction with respect to the optical waveguides. During insertion of the optical plug into a lug housing, the protective bracket, is moved relative to the optical waveguides, so that they project beyond the protective bracket.

Optoelectronic module and plug arrangement


The present invention provides a sensor with a LUX off function and a method for switching off, and is applicable to the field of lighting control technologies. The sensor includes: a brightness detection module, a sensor module, an MCU control module and a drive module. In the present invention, a function of automatically switching off a load driving lamp is implemented, and energy consumption is effectively reduced.

Technical Field
The present invention belongs to the field of lighting control technologies, and in particular relates to a sensor with a LUX off function and a method for switching off.
Related Art
At present, most microwave sensors are used by a built-in lamp. A lamp light value of the lamp is a variable, which affects brightness detection of the microwave sensors differently. At dawn, an actual ambient LUX value is lower than a preset LUX value of a common microwave sensor, and the lamp is triggered to be switched on when somebody passes by at the moment. Because there is no LUX off function, when people keep passing by during a delay time, the delay time is refreshed constantly to keep the lamp on, and even though the external natural light is very bright, the load lamp is not switched off. In this way, energy is wasted.

Sensor with LUX off function and method for switching off