Featured are devices and systems embodying one or more electrically-addressable-solid-state nanopores useful for sensing and/or characterizing single macromolecules as well as sequencing DNA or RNA. In one aspect of the present invention, there is featured a linear or 2-D electrically-addressable array of nanopores, where the nanopores are located at points of intersections between V-shaped grooves formed in an upper surface of the insulating member and a V-shaped groove formed in a lower surface of the insulating member. In another aspect of the present invention the solid-state nanopore of the present invention the width and/or length of the nanopore is defined or established by sharp edges of cleaved crystals that are maintained in fixed relation during the formation of the insulating member including the nanopore.

The present invention relates generally to nanopore and micropore devices and methods for their manufacture and use. More particularly the present invention relates to nanopore and micropore devices used for detecting, and characterizing biomolecules, as well as sequencing nucleic acids, and new methods for fabrication and application thereof.
Nanopores and micropores are structures that are useful and implemented for a wide range of applications. Nanopores are holes with diameters in the range of 100 nm to 1 nm in a membrane or solid media. Micropores refer to holes with diameters ranging from 100 nm to 100 μm. For nanopores, many applications have been contemplated including rapid detection and characterization of biological agents, and DNA sequencing. Micropores are already widely used as a mechanism for separating cells.
For the applications of DNA sequencing, two prior-art methods have been proposed using nanopores. U.S. Pat. No. 5,795,782, issued to Church et al. discloses a method of reading DNA sequence by detecting the ionic current variations as a single-stranded DNA molecule moving through the nanopore under a bias voltage. Another method for DNA sequencing using nanopores was discussed in U.S. Pat. No. 6,537,755, issued to Drmanac. Drmanac proposes to use nanopores to detect the DNA hybridization probes (oligonucleotides) on a DNA molecule and recover the DNA sequence information using the method of Sequencing-By-Hybridization (SBH).
Other applications using nanopores have been discussed widely in literature, including real-time monitoring of cell activities and detection of biological agents in biodefense. For many of these important applications, it is highly desirable to develop nanopore devices using solid-state materials. Here solid-state materials are broadly defined including high-density materials such as silicon oxides and nitrides, and polymeric materials such as hard plastics, as they are naturally insulating or can be insulated by adding a surface layer or making the surface insulating, e.g. by oxidization.
A well-known technique for producing nanoscale holes in solid-state materials uses high-energy particles to create damage tracks. The tracks become nanoscale holes when etched. Because a freestanding nanometer-thick film is mechanically unstable, the nanopores produced by this technique often have length on the order of a micrometer or more and are typically limited by the thickness of the starting film. For example, such long nanopores (also called nano-capillaries) were used by Bohn et al., in US Patent Publication No. 2003/0136679 and Kuo et al., in "Hybrid three-dimensional nanofluidic/microfluidic devices using molecular gates", Sensors and Actuators A, vol. 102 (October 2002): 223-233. Such long nanopores are not suitable for many applications such as DNA sequencing as currently discussed. Recent efforts in this field have been focused on developing new techniques for fabricating short nanopores having a pore length that is less than 20 nm.
U.S. Pat. No. 6,464,842, issued to Golovchenko et al. proposed a film-thinning technique. In the disclosed method, a shallow cavity is first created on one side of a membrane; the membrane is then thinned down from the opposite side slowly using a low-energy ion beam. Utilizing an active feedback loop to control the application of the low-energy ion beam, one can stop the thinning process as soon as a pore is opened at the cavity. This technique has been further developed into a nanoscale "sculpting" approach, [see Li et al., "Ion-beam sculpting at nanometer length scales", Nature, vol. 412 (July 2001): 166-169]. The main drawback of this approach is that highly specialized and expensive ion-beam instrumentation is needed.
In U.S. Pat. No. 6,503,409, Fleming proposes a method of making a nanopore (or nano-aperture) using silicon technology. In Fleming's approach, a nanopore is formed at the crossing point of two nanoslits. The nanoslits are fabricated by etching away a thin (2-5 nm) layer of sacrificial material. Because the pore size is controlled by the thickness of the sacrificial layer, the channel connecting to the pore is also of 2-5 nm in thickness. This feature is highly undesirable since the DNA molecules will be less likely to access the pore due to the large penalty in free energy (known as the entropic barrier) they have to overcome to reach the pore.
To take advantage of the silicon technology while avoiding the limit of the Fleming approach, Storm et al. [Storm et al., "Fabrication of solid-state nanopores with single-nanometer precision", Nature Materials, vol. 2 (August 2003): 537-540.] proposed a different method. Storm et al. used standard electron-beam lithography to create a 100 nm etch mask on the surface of a silicon membrane. When this mask is exposed to KOH solutions, an inverse pyramid feature is developed due to the anisotropy of the etching rate along different crystalline axes. Storm et al. showed that one can simply control the etching time so that a pore of 20 nm is opened on the opposite side of the etch mask. After oxidization, the silicon around the pore opening is turned into silicon oxide (SiO2). In the next step the SiO2 material around the pore is fluidized using a high-energy electron beam, such that the surface tension of the fluidized SiO2 pulls the material into the empty space thereby reducing the pore size. This technique has been shown to have great reliability in producing nanopores with diameters ranging from 1-20 nm. The pores can also be completely closed off using the same technique.
There are at least two major limitations in all of the above discussed techniques related to nanopore fabrication. The first is that all of the above techniques only produce individual pores. A single nanopore in a membrane will have very low throughput in molecule sensing operations. Accordingly, it is highly desirable to have an array of nanopores on the same membrane. However, a device using a membrane with many parallel pores will not be useful, since one cannot determine which pore a DNA is moving through. Second, all of the above techniques produce nanopores having pore length on the order of 10 nm or more.
In order to make the nanopores useful for practical applications, one needs to create a high-throughput device such as an array of nanopores wherein each pore in the array is independently electrically addressable. It would be desirable to provide a device and method that yields a linear array of nanopores or two-dimensional array of nanopores. It also would be particularly desirable to provide such linear and two-dimensional nanopore arrays that are electrically addressable. It would further be desirable to provide a new nanopore that can be formed using synthetic material and a method for using and making such a nanopore. It also would be desirable to provide a nanopore or an array of nanopores each with a length of less than 10 nm. It would be highly desirable to have simplified processes for fabricating nanopores and related fluidic systems at low cost.

Addressable nanopores and micropores including methods for making and using same


An animal brushing arrangement and method wherein a support part, a brush, an electric motor and a rotation sensor are provided. The electric motor is arranged to rotate the brush about a rotation axis, and the rotation sensor is arranged to detect a rotational movement about the rotation axis that is caused by an external force applied to the brush, such as by an animal, when the motor is not operating, a detection of such a rotational movement being operative to activate the motor.

Some animal brushing arrangements for brushing larger animals such as livestock, horses, pigs, etc., are mounted to a support structure and provided with a rotating brush which is driven by an electric motor, either directly or via a gear box. The brush is provided with bristles which, when the brush is rotated, interact with the fur and skin of an animal. The animal is thus brushed, scratched and/or groomed by the rotating brush.
In a particular kind of such animal brushing arrangements the rotating brush is suspended at one end from a brush carrying arrangement. The brush carrying arrangement comprises one or more parts, which allow the brush to swing back and forth in at least one plane. The brush may thus be moved by an animal when leaning against the brush to reach different parts of the body of the animal. Such animal brushing arrangements may be provided with the electric motor attached to the brush carrying arrangement above the rotating brush, as disclosed in e.g. EP 1487258, EP 1665927 and WO 2012/005654. Alternatively, such an animal brushing arrangement may be provided with the electric motor arranged inside the brush, as disclosed e.g. in EP 2422617.
The electric motor of such a brushing arrangement is started and stopped in order to start and stop a rotation of the rotating brush. In particular, it is desirable to provide on-demand brushing when an animal is yearning to be brushed, e.g. by leaning against the brush. Thus, energy may be saved when no animal is present to be brushed. EP 2271203 and EP 2422617 disclose the use of sensors or switches for controlling brush rotation. EP 2271203 discloses a sensor arranged to detect, by means of markings on a wall mounted mounting plate, a direction of pivoting of a casing of the brush. The alternative use of an inclinometer or inclinodetector is also mentioned. A direction of rotation of the brush is based on the detection. EP 2422617 discloses a switch mounted on a portion of a carrier of the brush. The switch is actuated by an angle bar arranged on a further portion of the carrier, when the brush and the further portion perform a pivoting motion in relation to the switch.
It has been realized by the inventor that small animals such as calves and goats may not be strong enough to lift a brush sufficiently to trigger a switch arranged on parts of the carrying arrangement of a rotating brush.

Animal brushing arrangement and method of operating animal brushing arrangement


The methods/systems described herein facilitate large-scale data collection and aggregation. One exemplary system that facilitates large-scale reporting of health-related data comprises a data collection component, a database and an aggregation component. The data collection component can collect health-related data on a large-scale from a non-selected population. The database can store at least some of the health-related data. The aggregation component can facilitate automatically ascertaining at least one pattern from the health-related data at least in part by applying one or more statistical, data-mining or machine-learning techniques to the database. One exemplary method of extracting health observations from information obtained on a macro-scale comprises receiving information about a plurality of self-selected subjects, pooling the information, mining the pooled information at least in part by employing a data-mining algorithm to infer one or more health observations from the pooled information, and monetizing the one or more health observations.

Many industries benefit from information technologies (IT) that facilitate collecting and drawing conclusions from aggregated data. Generally, the larger the data set, the better the conclusions that can be drawn from the data. However, such a task is complex, time-consuming and costly to perform on a large-scale.
Moreover, some industries face unique IT obstacles that further increase the difficulties of large-scale data acquisition and management. For instance, because health histories generally are stored in private, non-uniform databases, assembling this data on a large-scale would be extremely expensive. By way of another example, collecting and aggregating drug safety information is an important but challenging IT task. To address the potential for harmful drug effects, many countries establish government agencies to approve a pharmaceutical or medical device product before it can be sold to the public. These agencies usually require proof of efficacy and of an acceptable safety profile before the pharmaceuticals and medical devices are approved for sale. Typically the proof is obtained by conducting clinical trials on selected populations. These trials usually take many months and are quite expensive to conduct. In addition, some countries have post-market surveillance mechanisms in place, such as mandatory and voluntary adverse event reporting. However, delays inherent in the current systems have resulted in medications and devices with unacceptable risks remaining on the market during the time the data is being collected and aggregated.

Large-scale information collection and mining


Transient internal combustion engine fueling control with reduced calibration burden and increased precision through application of a convection model to estimate the mass transfer of fuel between cylinder intake gasses and intake system components primarily as a function of fuel film temperature and gas flow across fuel film on such components. The convection model applies potential/flow conditions in proximity to fuel film on intake components of an engine cylinder to predict the depletion of the fuel film and generates an impact factor representing the fraction of injected fuel impacting intake system components in a manner providing fuel control stability. The convection model applies an intake valve temperature estimate generated simply as a function of air mass flow rate through the intake system to be used in the calculation of the film convection parameters.

Ambitious automotive internal combustion engine emissions, fuel economy and performance goals require precise control of the ratio of air to fuel available for consumption in engine cylinders. Precise air/fuel ratio control requires compensation for fueling lags associated with the fuel injection system, including fueling lags caused by fuel film build-up on engine cylinder intake system components, such as valve poppets and intake passage walls. For a given fuel injection event, a portion of the fuel injected into a cylinder intake runner (passage) leading to an engine cylinder impacts the walls and intake valve poppet, leading to an accumulation or mass transfer of fuel film to such intake system components. That fuel film gradually depletes and is drawn, along with later injected fuel, into the engine cylinder during subsequent cylinder intake events, for combustion therein. The mass of fuel transferred to the intake system components and the time rate of depletion of that fuel is conventionally modeled as a boiling process.
For a given engine application, a substantial number of calibration parameters are required to account for the fuel mass transfer under the boiling process model. The need for a large set of calibration parameters is mainly due to the non-physical, weak relationship between the independent variables (i.e. intake manifold pressure and coolant temperature) used to schedule the parameters and the actual conditions occurring in the engine intake system. Accordingly, a significant amount of time is required to model the fuel mass transfer process each time an engine or engine intake system is changed, adding significant lead time and cost to engine development. Additionally, due to the lack of a clear underlying theory of parameter behavior, calibration parameter results vary significantly between applications due to differences in the approaches and expectations of calibration personnel.
It would therefore be desirable to provide a simplified model of the mass transfer process for transient internal combustion engine cylinder fueling control that accurately models the mass build-up and depletion of fuel film on the intake system, to provide for accurate control with reduced calibration burden.


Charges stored in a non-volatile semiconductor memory cell are erased in a manner that reduces leakage current. The cell includes source and drain regions formed on one surface of a semiconductor substrate. A channel region is defined by the source and drain regions. A tunnel oxide layer is formed over the channel region and a floating gate layer is formed on the tunnel oxide layer to store the charges. A control gate layer is formed over the floating gate. A first positive voltage is applied to the source region and a negative voltage is applied to the control gate layer. A second positive voltage is applied to the substrate. The combination of applied voltages reduces leakage current, in turn improving cell operating performance.

1. Field of the Invention
The present invention relates to non-volatile semiconductor memory cells and more particularly to a method and apparatus for erasing data stored in electrically erasable programmnable read only memories (EEPROMs) that reduces band-to-band leakage current.
2. Description of the Related Art
Conventional erasable programmable read only memories (EPROMs) include a multiplicity of memory cells. Each memory cell of a typical metal oxide semiconductor device has a floating gate layer located underneath a control gate layer. A channel layer is defined by drain and source regions on the surface of a semiconductor substrate. The floating gate layer lies over the channel layer and is completely insulated from other portions by an insulating layer such as a SiO.sub.2 layer.
Programming of data in the EPROM is usually carried out by applying 10 to 20 or more volts between the drain and source regions and applying an appropriate voltage to the control gate. Application of these voltages cause electrons to be accelerated across the channel layer, thereby producing electron-hole pairs by impact ionization. Once these electrons gain sufficient energy, they overcome the potential barrier of a gate oxide layer on the channel and inject into the floating gate layer. The injected electrons increase a threshold voltage of the memory cell. Thus, the memory cell can store a logic state "1" or "0" different from the initial erased state.
In an erasing operation, ultra-violet (UV) light is irradiated to the floating gate. Electrons stored in the floating gate absorb the exiting UV energy. The exiting electrons are carried away to the substrate through the gate oxide, causing the cells to store the erased state.
One improvement for such EPROMs is an electrically erasable and programmable read only memory (EEPROM). The EEPROM includes a control circuit for controlling programming and erasing operations. A voltage multiplying circuit generates high voltages, necessary for programming and erasing data from a single power source, such as 5 volts. EEPROMs are currently in wider use than EPROMs due to the simplicity of their programming and erasing. For example, one use for EEPROMS is in integrated circuit cards.
Referring to FIG. 1, symmetrical source region 6 and drain region 4 are doped with N+ impurities and are formed on a p-type semiconductor substrate 2. The source region 6 and drain region 4 are separated by a channel region over which is positioned a tunnel oxide layer having a thickness of about 100 .ANG.. A floating gate 8 is positioned on the tunnel oxide layer. An intermediate insulating layer of oxide-nitride-oxide (ONO) having a thickness of about 250 .ANG. is formed on the floating gate 8. A control gate 10 is positioned on the intermediate insulating layer. Thus, the transistor cell has a stack type structure.
Another prior art EEROM structure is shown in FIG. 2 and an EEPROM structure used in the present invention is shown in FIG. 3. The EEPROM structures in FIGS. 2 and 3 are substantially identical to the structure shown in FIG. 1, except for the technique and structure for erasing data. Thus, the explanation of the structures shown in FIGS. 2 and 3 will be omitted to avoid duplication.
Referring to FIG. 1, the cell is erased by applying a high voltage Vpp, such as 12 volts, to the source region 6, holding the control gate 10 and the substrate 2 at ground potential and floating the drain region 4. This erasing approach has an advantage of reducing the applied erase voltage Vpp to about 12 volts as compared with a bulk erasing in which an erase voltage of about 20 volts is applied to the substrate.
The potential difference of 12 volts between the substrate 2 and the source region 6 produces a leakage current. Also, the potential difference of 12 volts between the source region 6 and the control gate 10 through the thin tunnel oxide causes a portion of the source region 6, overlapping the floating gate 8, to be deep-depleted. A small amount of charge is injected into the thin tunnel oxide layer, lowering the potential barrier of the tunnel oxide, for electron tunneling (i.e. causing band-bending). Thus, the presence of the high potential difference between the source region 6 and control gate 10 results in another leakage current referred to as a band-to-band leakage current.
These leakage currents disturb normal erasing operations of the cell. For example, a typical EEPROM chip with a single power supply includes a voltage multiplying circuit for generating high erase and program voltages. If a block erasing operation of the chip is performed, a multiplicity of cells in the block must be simultaneously erased. Due to the leakage currents in each cell, the constant current capacity of the voltage multiplying circuit is insufficient for erasing all of the cells in the block. Thus, the cells cannot be erased.
FIG. 2 shows a prior art method of erasing data in a transistor cell. Erasing is performed by applying a supply voltage Vcc to a N+ source region 6, applying negative 10 volts to control gate 10, floating N+ drain region 4 and grounding the substrate 2. The lowered voltage of the source region decreases a source-substrate junction leakage current. However, the potential difference between the source region 6 and the control gate 10 does not considerably reduce the band-to-band leakage current. The electric field across the thin tunnel oxide layer is slightly greater than that in FIG. 1 and the electron-tunneling induced hole generation in the oxide layer is no less than that in FIG. 1. Thus, the transistor in FIG. 2 is no more effective in reducing the total leakage current than the transistor in FIG. 1.
As discussed above, electron tunneling, alternatively referred to as Fowler-Nordheim tunneling, occurs through a small tunneling region of the thin tunnel oxide layer overlapping the source region 6 and the floating gate 10. Since reprogramming cells requires the cells also be erased, every cell must generally keep a constant threshold voltage over a certain number of program-erase cycles. In the case of block erasing, threshold voltages of cells (bits) in the block must be densely distributed at a desired voltage, regardless of the number of program-erase cycles.
The tunnel oxide layer at the small tunneling region is stressed by the repeated erasing cycles. Repeated erasing cycles increase the number of holes trapped in the oxide layer causing changes in the threshold voltage. Variations in manufacturing conditions also cause variations in oxide thickness. This means that every cell in the block may not be erased to the same desired threshold voltage. Thus, block erased cells might not have a close distribution of threshold voltages. Therefore, it is necessary that during the erasing operation of the chip, the holes trapped in the tunnel oxide layer are reduced.
It is therefore an object of the present invention to provide a method of reducing band-to-band leakage current during erasing operations in nonvolatile semiconductor memory cells.
It is another object of the present invention to reduce holes trapped in a thin tunnel oxide during erasing operations in a nonvolatile semiconductor memory cell.

Method for erasing electrically erasable and programmable memory cells


Angiogenic endothelial cells are selectively targeted with lipid/DNA complexes or cationic liposomes containing a substance which affects the targeted cells by inhibiting or promoting their growth. A site of angiogenesis can be precisely located by administering cationic liposomes containing a detectable label. The complexes may comprise nucleotide constructs which are comprised of promoters which are selectively and exclusively activated in the environment of an angiogenic endothelial cell.

The present invention can be applied to the treatment and diagnosis of a variety of different diseases and abnormalities. Although the present invention is not limited to such, it can be used in the treatment of cancer, wound healing, and a variety of chronic inflammatory diseases. In general, each is presently treated directly by physical means such as surgical removal of cancerous tissue, suturing of wounds and surgical removal of inflamed joints. Further, each can be treated by chemical means. Chemotherapy is applied to cancers, growth hormones are applied to wound healing and anti-inflammatory drugs are applied to treating chronic inflammatory conditions. These, and related treatments are directed, in general, to treating the cancerous, injured, or inflamed tissue directly. In order to provide an understanding on how the present invention departs from conventional treatment modalities a brief and general description of current treatment technologies in these areas is provided.
Cancer Treatments
The term "cancer" encompasses a spectrum of diseases that vary in treatment, prognosis, and curability. The approach to diagnosis and treatment depends on the site of tumor origin, the extent of spread, sites of involvement, the physiologic state of the patient, and prognosis. Once diagnosed, the tumor is usually "staged," a process which involves using the techniques of surgery, physical examination, histopathology, imaging, and laboratory evaluation to define the extent of disease and to divide the cancer patient population into groups in order of decreasing probability of cure. Such systems are used both to plan treatment and determine the prognoses for the patient (Stockdale (1996) "Principles of Cancer Patient Management," In: Scientific American Medicine, vol. 3, Dale, D. C., and Federman, D. D. (eds.), Scientific American Press, New York). The type or stage of the cancer can determine which of the three general types of treatment will be used: surgery, radiation therapy, and chemotherapy. An aggressive, combined modality treatment plan can also be chosen. To this end, surgery can be used to remove the primary tumor, and the remaining cells are treated with radiation therapy or chemotherapy. Rosenberg (1985) New Engl. J. Med. 312:1512-14.
Surgery plays the central role in the diagnosis and treatment of cancer. In general, a surgical approach is required for biopsy, and surgery can be the definitive treatment for most patients with cancer. Surgery is also used to reduce tumor mass, to resect metastases, to resolve medical emergencies, to palliate and rehabilitate. Although the primary surgical technique for cancer treatment has involved the development of an operative field where tumors are resected under direct visualization, current techniques allow for some resections to be performed by endoscopic means. A primary concern in the treatment of cancer is the consideration of operative risk (Stockdale, F., supra).
Radiation therapy plays an important role in both the primary and palliative treatment of cancer. Both teletherapy (megavoltage radiation therapy) and brachytherapy (interstitial and intracavity radiation) are in common use. Electromagnetic radiation in the form of x-rays is most commonly used in teletherapy to treat common malignant tumors, while gamma rays, a form of electromagnetic radiation similar to x-rays but emitted by radioactive isotopes of radium, cobalt, and other elements, are also used. Radiation therapy transfers energy to tissues as discrete packets of energy, called photons, that damage both malignant and normal tissues by producing ionization within cells. The target for the ions is most commonly the DNA; radiation therapy exploits the fact that the radiation damage is not uniform between malignant and non-malignant tissues—rapidly dividing cells are more sensitive to DNA damage than quiescent cells (Pass (1993) J. Natl. Cancer Instit. 85:443-56.) Radiation therapy is associated with unique benefits as well as important toxicities. Radiation is preferred in certain anatomic areas, (e.g., the mediastinum), where radiation may be the only feasible local method of treatment, and radiation may also be the only feasible local modality if tumor involvement is extensive. Radiation may also be used when the patient finds surgery unacceptable, or when the patient's medical condition prohibits a surgical procedure. Radiation treatment involves tissue damage which can lead to early and late radiation effects. The early effects (acute toxicity of radiation therapy) include erythema of the skin, desquamation, esophagitis, nausea, alopecia, and myelosuppression, while the late effects include tissue necrosis and fibrosis, and usually determine the limiting toxicity of radiation therapy (Stockdale, F., supra).
Nearly all chemotherapeutic agents currently in use interfere with DNA synthesis, with the provision of precursors for DNA and RNA synthesis, or with mitosis, and thus target proliferating cells (Stockdale, F., "Cancer growth and chemotherapy," supra). Animal tumor investigation and human clinical trials have shown that drug combinations produce higher rates of objective response and longer survival than single agents (Frei (1972) Cancer Res. 32:2593-2607). Combination drug therapy uses the different mechanisms of action and cytotoxic potentials of multiple drugs, including the alkylating agents, antimetabolites, and antibiotics (Devita, et al. (1975) Cancer 35:98-110). The physiologic condition of the patient, the growth characteristics of the tumor, the heterogeneity of the tumor cell population, and the multidrug resistance status of the tumor influence the efficacy of chemotherapy. Generally, chemotherapy is not targeted (although these techniques are being developed, e.g. Pastan (1986) Cell 47:641-648), and side effects such as bone marrow depression, gastroenteritis, nausea, alopecia, liver or lung damage, or sterility can result.
Wound Healing
Wound healing is a complex and protracted process of tissue repair and remodeling involving many different cell types which requires a finely tuned control of various biochemical reaction cascades to balance the regenerative processes. Wound healing is generally divided into three phases: inflammation, proliferation, and maturation (Waldorf, et al. (1995) Adv. Dermatol. 10:77-96). The process comprises the migration of different cell types into the wound region, growth stimulation of epithelial cells and fibroblasts, formation of new blood vessels, and the generation of extracellular matrix. The correct functioning of these processes depends on the biological activation of various cytokines (Bennett, et al. (1993) Am. J. Surg. 165:728-37). Nutrition, the immune system, oxygen, blood volume, infection, immunosuppression, and a decrease in red blood cells are all influential factors in wound healing (Witney, (1989) Heart Lung 18: 466-474).
The quality as well as the rate of wound healing is usually dependent on the type and extent of the original injury. Three general types of process are used to treat wounds, each of which is directed to healing the damaged tissue. Closure of wounds is most commonly accomplished by suturing, although tapes, stapling or electrocautery can also be used (Wheeless, C. R., 1996, Wheeless' Textbook of Orthopaedics) (Garrett, et al. (1984) J. Hand. Surg. 9(5):683-92). Skin tapes and various sutures each exhibit certain benefits and disadvantages in primary closure of wounds. Skin tapes cause less inflammatory reaction but fail to close the subepithelial wound spaces, while the inflammatory reaction and subsequent scarring caused by various sutures depends upon the size of the suture needle, the diameter of the suture material, and whether it is a monofilament or woven suture (Simpson, (1977) Laryngoscope 87: 792-816).
In a wound, the size of an inoculum of microorganisms, the virulence of the organisms, and host antimicrobial defense mechanisms determine if an infection will develop. Thus, antibiotics can also be of therapeutic value in the treatment of wounds (Edlich, (1986) Emergency Medical Clinics of North America 4(3):561-80). The pharmacological action of each antibiotic must be understood in order to choose the proper antibiotic, its route of administration, and to avoid side effects (Simpson, supra). Recent results suggest that antibiotic therapy allows cell proliferation and differentiation to proceed more rapidly and thus may be helpful in augmenting wound repair (Barrow, et al. (1994) Respiration 61:231-5; Maeder, et al. (1993) Paraplegia 31: 639-44). Proteolytic enzymes have also been used as adjuncts to antibiotic treatment of contaminated wounds (Rodeheaver, et al. (1978) Am. J. Surg. 136(3):379-82).
The topical administration of various cytokines, including bFGF, EGF, PDGF, and TGF-beta, either alone or in combination, may considerably accelerate wound healing (Moulin, (1995) Eur. J. Cell. Biol. 68:1-7). Growth factors attract cells into the wound, stimulate their proliferation, and have profound influence on extracellular matrix deposition. Since developing the ability to mass-produce these cytokines by recombinant techniques, many studies have demonstrated that growth factors can augment all aspects of tissue repair in normal and impaired healing models (e.g., Schultz, et al. (1987) Science 235: 350-2; Deuel, et al. (1991) Annu. Rev. Med. 42: 567-84). Although preliminary clinical trials have shown that growth factor treatment has occasionally led to statistically significant improvements in tissue repair, it is not clear that these results are clinically significant, and it has been suggested that new clinical trials must focus on targeting growth factors for specific types of impaired healing (Greenhalgh, (1996) J. Trauma 41:159-67).
Chronic Inflammation
Natural, humoral, and cellular immune mechanisms have all been implicated in the pathogenesis of chronic inflammatory diseases (Seymour, et al. (1979) J. Oral. Pathol. 8:249-65). Autoimmune diseases result from abnormalities in lymphocyte function. Abnormalities in T cell function can be responsible for disease through cell-mediated immunity, and the activity of helper T cells in the production of antibodies may contribute to autoantibody formation. The central role of helper T cells in autoimmune disease is supported by the association of many of these diseases with certain HLA molecules. The failure of one or more steps in the maintenance of tolerance could result in autoimmunity (Robinson (1996) "Immunologic Tolerance and Autoimmunity," in: Scientific American Medicine, Vol. 2, Section VI, Scientific American Press, New York, p. 1-11).
Several types of treatment are used in autoimmune disease, all of which are directed at lessening the immune response in the affected tissue. For example, treatment for rheumatoid arthritis, an autoimmune disease, can utilize anti-inflammatory agents such as nonsteroidal anti-inflammatory agents (NSAIDs) or glucocorticosteroids, remission inducing agents such as gold salts, and/or immunosuppressive drugs such as cyclophosphamide. Orthopedic surgery can also be used to replace joints damaged during the inflammatory process (see Gilliland, B. C., and Mannik, M., 1983, "Rheumatoid Arthritis" In: Harrison's Principles of Internal Medicine, McGraw Hill, New York, P. 1977-1984). Recent work has suggested the possibilities of new treatments, also directed to the affected tissue, such as the use of TNFα in the treatment of rheumatoid arthritis (Brennan, et al. (1995) Br. Med. Bull. 51:368-384).
Allergy refers to a condition in which the immune response to environmental antigens causes tissue inflammation and organ dysfunction. As in the autoimmune diseases, the data suggest an interaction of several components of the immune system in allergic diseases. The diversity of expression of allergic diseases arises from different immunologic effector mechanisms, which evoke specific patterns of tissue injury (Beer, et al. (1996) "Allergy," In: Scientific American Medicine, Vol. 2, Section VII, Scientific American Press, New York, P. 1-29). The clinical features of each allergic disease reflect the immunologically mediated inflammatory response in the affected organs or tissues (e.g. asthma reflects an inflammatory response in the airways).
Several treatment strategies are used to treat the immune-mediated allergic diseases, all of which are directed at lessening the immune response in the inflamed tissue. For example, in the treatment of asthma, therapy can involve environmental control, pharmacotherapy, and allergen immunotherapy (Beer, et al. (1996) "Allergy," In: Scientific American Medicine, Vol. 2, Section VII, Scientific American Press, New York, pp. 1-29). In the treatment of asthma, elimination of the causative agent is the most successful means of preventing the inflammation. However, this is often not possible, and thus several classes of drugs have been used. These include the methylxanthines (for bronchodilation), adrenergic stimulants (stimulation of α-adrenergic receptors, bronchodilators), glucocorticoids (lessen inflammation in the lung), chromones (downregulate mast cells, lessen inflammation in the lung), and anticholinergics (bronchodilators) (McFadden, et al., "Lung disease caused by immunologic and environmental injury," In: Harrison's Principles of Internal Medicine, McGraw Hill, New York, p. 1512-1519). Desensitization or immunotherapy with extracts of the suspected allergens has also been suggested in order to reduce inflammation in asthma (McFadden and Austen, op. cit.; Jacquemin and Saint-Remy (1995) Ther. Immunol. 2:41-52).
Atherosclerotic Plagues
Atherosclerosis is the progressive narrowing of the lumen (inner passageway) of arterial blood vessels by layers of plaque (fatty and fibrous tissues). The major complications of atherosclerosis, including ischemic heart disease, myocardial infarction, stroke, and gangrene of the extremities, account for more than half of the annual mortality in the United States.
Arteries are composed of three layers: the intima, which comprises endothelium and connective tissue on the luminal side of the internal elastic lamina; the media, which comprises smooth muscle cells and, in the elastic arteries, elastic fibers, and, in large vessels, the vasa vasorum; and the adventitia, which is the external layer of the vessel wall and comprises a connective tissue sheath composes of fibroblasts, small vessels, and nerves. Atherosclerosis can occur in any artery. In coronary arteries, it may result in heart attacks; in cerebral arteries it may result in strokes; and in peripheral arteries it may result in gangrene of the extremities. Atherosclerosis is a complex process, and precisely how it begins or what causes it is not known. However, endothelial injury is believed to be an initial step in the formation of atherosclerotic lesions, and may be caused by hemodynamic strain, hypercholesterolemia, hypertension or immune complex disease. Endothelial injury leads to cholesterol and lipid accumulation, intimal thickening, smooth muscle cell proliferation, and formation of connective tissue fibers. Gradually, the build-up of fatty deposits and the proliferation of the smooth muscle cells lead to the formation of plaques which eventually narrow and block the artery.
Neovascularization within the intima of human atherosclerotic lesions has been described, but its role in the progression of atherosclerosis is unclear. Moulton, et al. (1999) Circulation 99:1726-1732; Isner (1999) Circulation 99:1653-1655; Depre, et al. (1996) Catheterization and Cardiovascular Diagnosis 39:215-220.
The mortality rate due to atherosclerosis and related pathologies makes it clear that current treatments are inadequate. The factor most important in causing atherosclerotic events is a high blood plasma concentration of cholesterol in the form of low-density lipoproteins. Current methods of treatment include drugs which inhibit the liver enzyme system for cholesterol synthesis.
Current Treatments—Immunology
The treatment regimes described above have had varying degrees of success. Because the success rate is far from perfect in many cases research continues to develop better treatments. One promising area of research relates to affecting the immune system. By the use of genetic engineering and/or chemical stimulation it is possible to modify and/or stimulate immune responses so that the body's own immune system treats the disease e.g., antibodies destroy cancer cells. This type of treatment departs from those described above in that it utilizes a biological process to fight a disease. However, the treatment is still a direct treatment meaning that the antibodies created directly attack the cancer cells.
The present invention can be utilized for treatments which involve a radical departure from normal treatments in that the present invention does not involve directly affecting the cancerous, damaged or inflamed cells.
Others have recognized that, at least theoretically, it is possible to treat cancer or inflammation associated with angiogenesis by inhibiting the angiogenesis. A typical example of the current thinking relating to such is discussed within PCT Publication WO 95/25543, published Sep. 28, 1995. This published application describes inhibiting angiogenesis by administering an antibody which binds to an antigen believed to be present on the surface of angiogenic endothelial cells. Specifically, the application describes administering an antibody which binds to αvβ3 which is a membrane receptor believed to mediate cell-cell and cell-extracellular matrix interactions referred to generally as cell adhesion events. By blocking this receptor the treatment hopes to inhibit angiogenesis and thereby treat cancer and inflammation.

This patent is subject to a terminal disclaimer.

Cationic liposome delivery of taxanes to angiogenic blood vessels

The Regents of the University of California


The clip structure is provided for securing the microphone of a vehicle telephone in a position beneath the forward marginal edge portion of a vehicle headliner with a microphone cable extending around the forward edge of the vehicle headliner into the space between the vehicle headliner and the vehicle roof structure. The clip structure includes means for securing the microphone in place, means for securement of the structure to the headliner and means for retaining the microphone cable in place.

1. Field of Art
The present invention relates to a clip structure for securing the microphone of a vehicle telephone to the forward marginal edge portion of a vehicle headliner.
2. Prior Art
Cellular telephones have become a popular accessory item for vehicles. Current technology has permitted the desired use of such telephones in vehicles at a relatively low cost as compared with previous vehicle telephone systems.
One problem which has been encountered with vehicle telephones is the use of a handset of the type commonly used in office and home telephones for transmitting and receiving. The use of handsets is inconvenient for a driver. Desirably, a hands-free telephone system is preferred. This is currently being accomplished by stationary mounting of the receiver element and the transmitter element in a position in the forward compartment of a vehicle adjacent the driver's seat thereby permitting the driver to use the telephone without the inconvenience of holding a handset.
One type of transmitter currently being used for this purpose is a microphone mounted by means of bracket structure at the forward edge of the vehicle headliner or on the sunvisor. Prior art mounting structure has included three clip elements generally formed of sheet metal. These elements include a clip which attaches to either the headliner or visor, a second clip which mounts the microphone component, and a third clip for routing the microphone cable. Such mounting structure is visually objectionable in that is consists of three separate components not integrated into the vehicle interior design. Assembly is also somewhat costly in that three separate parts have got to be mounted by the assembly worker.
The present invention provides a single clip structure which incorporates three functionally independent clips molded into one unit. The structure is securable to the forward marginal edge of the vehicle headliner in a position convenient for use by the driver. The clip structure is desirably molded from a plastic material which results in an aesthetically appealing rounded structure. The clip structure includes an integrally formed channel that mounts the microphone cable above the headliner. The channel positively captures the microphone cable and protects it from damage by providing generous strain relief and a protective housing structure. Further, the channel permits right, left or straight-out cable routing.

Clip structure for mounting vehicle telephone microphone


When a two-dimensional tomogram is to be displayed, motion information associated with a direction orthogonal to the tomogram is colored and mapped on the tomogram to be visualized by using the volume data of a TSI image. For example, a mapping image is generated by color-mapping shortening information at each point on a cardiac tissue on a short axis view by using the volume data of the TSI image. Superimposing and displaying the mapping image on the original short axis view makes it possible to simultaneously observe the shortening information even while a short axis view is obtained and observed.

1. Field of the Invention
The present invention relates to the visualization of a heart by using the TSI (Tissue Strain Imaging) method and, more particularly, to the mapping of the shortening information of the heart in the long axis direction in a contraction phase to a short axis image or the mapping of the thickening information of the heart in the cardiac wall thickness direction to a short axis image.
2. Description of the Related Art
In general, with regards to a living tissue such as cardiac muscle, it is very important for the diagnosis of the tissue to objectively and quantitatively evaluate the motion or function of the tissue. In image diagnosis using an ultrasonic image processing apparatus, various quantitative evaluation methods have been tried mainly for heart cases. For example, it is known that the normal cardiac muscle thickens in the wall thickness direction (short axis), and shortens in the long axis direction in a contraction phase. It is generally said that the motion directions of thickening and shortening are perpendicular to each other and exhibit different mechanisms. It is suggested that evaluating the myocardial wall motion by observing these motions makes it possible to support diagnosis associated with a heart disease such as myocardial infarction.
In a conventional ultrasonic diagnostic apparatus, however, the following problems arise. While a short axis view is obtained and observed, no biometric information perpendicular to a scanning plane of the short axis view can be acquired due to the characteristics of the ultrasonic diagnostic apparatus. Therefore, shortening information cannot be simultaneously expressed. In addition, while a apical long axis approach is obtained and observed by, for example, the tissue Doppler method, thickening information cannot be simultaneously expressed because of a Doppler angle limitation.

Ultrasonic image processing apparatus, ultrasonic diagnostic apparatus, and ultrasonic image processing program


A fixing unit includes a current detection portion configured to detect a drive current of a pump unit and determines whether a valve unit is in an abnormal state corresponding to the output of the current detection portion.

1. Field of the Invention
The present invention relates to a fixing apparatus configured to fix a toner image onto a sheet and an image forming apparatus including the fixing unit.
2. Description of the Related Art
Image forming apparatuses configured to form an image using an electrophotographic method includes a fixing unit configured to fix a toner image onto a surface of a recording material (referred to as sheet or paper) by a transfer method or a direct method. When the fixing unit fixes the toner image, paper with the unfixed toner image is guided to pass through a nip portion formed by a pair of rollers (i.e., a heating roller with a heated surface and a pressure roller). While the paper passes through the nip portion, heat and pressure is applied to the sheet. Accordingly, the unfixed toner is fused and fixed to the surface of the paper.
Since the unfixed toner on the paper is fused when the paper passes through the nip portion, there has been a possibility that a jam is caused by the paper wrapping around the heating roller due to the viscous behavior of the toner. Conventionally, in order to avoid such a paper jam, the fixing unit, such as the one described above, uses a separation claw which contacts the heating roller to separate the paper wrapping around the heating roller.
The separation claw can easily separate the paper from the heating roller if the image density is low or if enough space is provided between the leading edge of the paper and the top of the image (hereinafter referred to as a margin). Meanwhile, for example, if paper of a small grammage (especially coated paper) is used or the toner image is a color image of increased density or, further, the margin of the paper is small, the paper tends to wrap around the heating roller. Thus, in such a case, the separation claw may not be able to appropriately separate the paper from the heating roller.
Further, since the separation claw contacts the heating roller, the claw may scratch the surface of the heating roller. In such a case, the scratch may be transferred to the fused toner and a defective image may be formed.
Under such circumstances, a separation method that does not form a scratch on the heating roller is discussed in Japanese Patent Application Laid-Open No. 2004-212954 and No. 2009-271345. According to the separation method, compressed air is jetted from a nozzle toward the heating roller to separate the paper from the heating roller. Further, according to the method discussed in Japanese Patent Application Laid-Open No. 2004-212954, air compressed by a pump is jetted from a solenoid valve in pulses to separate the paper.
However, as discussed in Japanese Patent Application Laid-Open No. 2004-212954 and No. 2009-271345, since the air compressed by a pump is blown out from a nozzle, if the solenoid valve fails due to, for example, its deterioration, it may result in a paper jam at the fixing unit. If the paper jam occurs due to a failed solenoid valve, processing for solving the jam takes time, which results in the downtime of the image forming operation. Thus, it is convenient if the failure of the solenoid valve can be detected in advance.

Fixing apparatus and image forming apparatus


Disclosed is a method and system for inserting a new data object in a data visualization with one or more other data objects already present on a canvas. The insertion of the new data object involves receiving a position of a new data object for the canvas from a user, determining a position of a first one of the one or more data objects and a second one of the one or more data objects on the canvas, determining an overlap pixel count, if the new data object is overlapping with the position of the first one of the one or more data objects, determining an action type on the first one of the one or more data objects based on the overlap pixel count, generating a preview of the canvas with the new data object and inserting the new data object on the canvas based on user approval.

Business intelligence data presents many challenges to user interface designers trying to find an optimal way for presenting the correct amount of data on limited screen space. By nature, business intelligence data tends to be voluminous not to mention contextual such as to a given user, to a given situation, to a given geography, etc. So many business intelligence tools including reporting tools, such as Crystal Reports by Business Objects, an SAP company provides a flexible platform for creating reports in real time which are accessible to most technology novices including casual business users.
Many reporting tools and other business intelligence applications combine raw data with other data visualization objects such as charts, graphs, etc. Business users want to be able to edit data visualizations dynamically by adding and removing data. However, such users are also very concerned about how the data visualization looks including fitting in the correct type and amount of data in the correct form within given screen limitations. Accordingly, they want to be able to preview how their desired changes will affect a current visualization of the data without actually implementing the change, for instance.
This need is more pronounced on a data visualization that already has data objects (e.g., fields in a report) displayed on an existing canvas. For instance, the current user interface of Crystal Reports requires a lot of manual effort when modifying a report such as by adding a data object into a set area. This effort is commonly referred to as pixel pushing. This experience can be made easier for data visualization authors and increase their productivity simultaneously.


The present invention provides mutant nucleotidylyl-transferases, such as Ep, having altered substrate specificity; methods for their production; and methods of producing nucleotide sugars, which utilize these nucleotidylyl-transferases. The present invention also provides methods of synthesizing desired nucleotide sugars using natural and/or modified Ep or other nucleotidyltransferases; and nucleotide sugars sythesized by the present methods. The present invention further provides new glycosyl phosphates, and methods for making them.

Many bioactive metabolites possess unusual carbohydrates required for molecular recognition. (See for example, Liu, H.-w.; Thorson, J. S. Ann. Rev. Microbiol., 1994, 48, 223–256; Weymouth-Wilson, A. C. Nat. Prod. Rep. 1997, 14, 99–110; In Macrolide Antibiotics, Chemistry, Biology and Practice; Omura, S. Ed., Academic Press: New York; 1984; Johnson, D. A.; Liu, H.-w. Curr. Opin. Chem. Biol. 1998, 2, 642–649; and Trefzer, A.; Salas, J. A.; Bechthold, A. Nat. Prod. Rep. 1999, 16, 283–299.) In fact, roughly 70% of current lead compounds in modern drug discovery derive directly from natural products, many of which are glycosylated metabolites. (See Thorson, J. S. et al. Nature's Carbohydrate Chemists: The Enzymatic Glycosylation of Bioactive Bacterial Metabolites. Curr. Org. Chem. manuscript in press, (2000); and references therein and Weymouth-Wilson, A. C. The Role of Carbohydrates in Biologically Active Natural Products. Nat. Prod. Rep. 14, 99–110 (1997)). Examples of pharmaceutically important glycosylated metabolites include, for example, amphotericin, megalomicin/erythromycin, mithramycin, doxorubicin, vancomycin and calicheamicin, as shown in FIG. 5. While it is known that the sugar moieties of these pharmaceutically important metabolites often define their corresponding biological activity, (see Weymouth-Wilson, A. C., The Role of Carbohydrates in Biologically Active Natural Products, Nat. Prod. Rep. 14, 99–110 (1997)), efficient methods to systematically alter these essential carbohydrate ligands are still lacking.
In metabolite biosynthesis, glycosylation begins with the nucleotidylyltransferase-catalyzed activation of a sugar phosphate as a nucleotide diphosphosugar (NDP-sugar) donor. After activation, a number of enzymatic processing reactions often occur (e.g., deoxygenation, transamination, oxidation/reduction, epimerization, alkylation, and decarboxylation) prior to the culminating glycosyltransferase-catalyzed attachment to the aglycon. (Liu, H.-w. & Thorson, J. S. Pathways and Mechanisms in the Biogenesis of Novel Deoxysugars by Bacteria. Ann. Rev. Microbiol. 48, 223–256 (1994); Kirschning, A., Bechtold, A. F-W. & Rohr, J. Chemical and Biochemical Aspects of Deoxysugars and Deoxysugar Oligosaccharides. Top. Curr. Chem. 188, 1–84 (1997); Johnson, D. A. & Liu, H.-w. Mechanisms and Pathways from Recent Deoxysugar Biosynthesis Research. Curr. Opin. Chem. Biol. 2, 642–649 (1998); Hallis, T. M. & Liu, H.-w. Learning Nature's Strategies for Making Deoxy Sugars: Pathways, Mechanisms, and Combinatorial Applications. Acc. Chem. Res. 32, 579–588 (1999); Johnson, D. A. & Liu, H.-w. In Comprehensive Chemistry of Natural Product Chemistry (Barton, D.; Nakanishi; K.; Meth-Cohn, O. eds), Elsevier Science, Oxford, 311, (1999); Trefzer, A., Salas, J. & Bechthold, A. Genes and Enzymes Involved in Deoxysugar Biosynthesis in Bacteria. Nat. Prod. Rep. 16, 283–299 (1999); and Bechthold, A. & Rohr, J. In New Aspects of Bioorganic Chemistry (Diederichsen, U.; Lindhorst, T. K.; Wessjohann, L.; Westerman, B., eds.) Wiley-VCH, Weinheim, 313, (1999)).
The glycosyltransferases that incorporate these essential ligands are thought to rely almost exclusively upon UDP- and TDP-nucleotide sugars; however some have demonstrated promiscuity towards the sugar donor, (e.g., Gal, D-galactose; Glc, D-glucose; Man, D-mannose; NTP, nucleotide triphosphate; pFPTC, pentafluorophenoxythiocarbonyl; TDP, thymidine diphosphate; TMP, thymidine monophosphate; TTP, thymidine triphosphate; UDP, uridine diphosphate.) Genetic experiments suggest that downstream glycosyltransferases in secondary metabolism are promiscuous with respect to their NDP-sugar donor, setting the stage for the expansion of "combinatorial biosynthesis" approaches to change metabolite glycosylation. (See Madduri, K. et al., Production of the antitumor drug epirubicin (4′-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetius Nat. Biotech. 16, 69–74 (1998); and Hutchinson, C. R. Combinatorial Biosynthesis for New Drug Discovery. Curr. Opin. Microbiol. 1, 319–329 (1998).) This information has led to the exploitation of the carbohydrate biosynthetic machinery to manipulate metabolite glycosylation, (Madduri, K.; Kennedy, J.; Rivola, G.; Inventi-Solari, A.; Filppini, S.; Sanuso, G.; Colombo, A. L.; Gewain, K. M.; Occi, J. L.; MacNeil, D. J.; Hutchinson, C. R. Nature Biotech. 1998, 16, 69–74; and Zhao, L.; Ahlert, J.; Xue, Y.; Thorson, J. S.; Sherman, D. H.; Liu, H.-w. J. Am. Chem. Soc., 1999, 121, 9881–9882 and references therein), revitalizing interest in methods to expand the repertoire of available UDP- and TDP-sugar nucleotides. (See Zhao, Y.; Thorson, J. S. J. Org. Chem. 1998, 63, 7568–7572; and Elhalabi, J. M.; Rice, K. G. Cur. Med. Chem. 1999, 6, 93–116.)
These in vivo methods are limited by both a particular host's biosynthetic machinery and the specific host's tolerance to each newly constructed metabolite. Further, in vitro progress in this area is limited by the availability of the required NDP-sugar substrates. (Solenberg, P. J. et al., Production of Hybrid Glycopeptide Antibiotics in vitro and in Streptomyces toyocaensis. Chem. & Biol. 4, 195–202 (1997).)
Thus, there is a need for a greater variety of available NDP-sugar substrates.
Salmonella enterica LT2 α-D-glucopyranosyl phosphate thymidylyltransferase (Ep) is a member of the prevalent nucleotidylyltransferase family responsible for the reversible conversion of α-D-hexopyranosyl phosphate and NTP to the corresponding NDP-sugar nucleotide and pyrophosphate. Of the many nucleotidylyl-transferases studied, the NDP-sugar nucleotide-forming thymidylyltransferases have received the least attention in prior work. (See Lindquist, L.; Kaiser, R.; Reeves, P. R.; Lindberg, A. A. Eur. J. Biochem. 1993, 211, 763–770, and Gallo, M. A.; Ward J.; Hutchinson, C. R. Microbiol. 1996, 142, 269–275.) Even in Ep, substrate specificity studies prior to the work of the present inventors were limited to only a few available hexopyranosyl phosphates. (See Lindquist, L.; Kaiser, R.; Reeves, P. R.; Lindberg, A. A. Eur. J. Biochem. 1993, 211, 763–770.)

Active-site engineering of nucleotidylyltransferases and general enzymatic methods for the synthesis of natural and “unnatural” UDP- and TDP-nucleotide sugars

Sloan-Kettering Institute for Cancer Research


A method and computer program are provided for controlling access to a memory device wherein, even with a complex data storage structure, access is made to memory areas within the memory device with a minimal number of selection inputs required for selection of a desired memory area.

The continuously increasing extent of the functionality of applications which are provided in data processing systems has resulted in the amount of data which needs to be controlled by the data processing systems increasing to a similar extent. The desire to use the extended functionality of applications (for example, for supporting complete business processes) is a further motivation for increasing networking of data processing systems and for increased integration of different applications provided there, in order to form workflow management systems. The increasing networking of data processing systems and the increased integration of applications have increasingly led to the need to take account of the problems associated with multiple access to memory devices in the data processing systems. Increasing amounts of data and multiple access not only result in new requirements for data maintenance and distribution, but also require new strategies for access to memory resources by data processing systems.
The present invention is, therefore, directed toward a method for fast and efficient control of access to a memory device, and a computer program for implementing the method.

Method for controlling the access to a storage device and a corresponding computer program


A system and method are disclosed for integrating an intelligent electronic device (IED) in a network management system. The IED may be configured to communicate using the network management protocol of the network management system. IED variables may be mapped to associated network management protocol variables to allow the network management system to access the IED variables using the network management protocol.

Advancements in, and demands for, technology have increased. In particular, high technology industries have increased their demands on the electrical power supplier, requiring more power, increased reliability and lower costs. A typical computer data center may use several hundred watts of energy per square foot compared to an average of 15 watts per square foot for a typical commercial building. Accordingly, the monitoring of energy usage and the detection of power quality events may be necessary for high technology industries.
Complex networks of computer and communications equipment may use a network management system to manage this equipment. One or more network management stations obtain information from the attached network devices using a network management protocol that communicates with agent software running on each device. Although network devices may offer a variety of performance data via the network management protocol, they do not have the ability to measure key parameters of the power system they are attached to.
The network management system, such as a computer network, may utilize energy meters and/or Intelligent Electronic Devices ("IED's") to monitor energy usage. The energy meters and/or IED's may be part of an energy management system that is independent of the network management system. The energy management system may communicate with a network protocol, such as the Modbus interface. The communication within the energy management system may be independent of the network management system that is being monitored.

Energy monitoring system using network management protocols


An improved device for holding chalk for application to pool cue tips which includes a walled housing that defines a chalk receiving chamber therewithin for receipt of a plurality of cubes of chalk in side-by-side fashion. A front wall of the device has an opening that is adequate in dimension to permit ready access of the tip of a pool cue therethrough for contact with the appropriate surface of the chalk of any one of the cubes that is located behind the slot and within the housing. The chalk holding device according to the present invention is intended for mounting to a support surface such as a wall of a table, building wall or the like so as to preferably present the face of the chalk cubes to a player at an angular relationship in a range of from about 12.degree. to about 45.degree. to the vertical to facilitate ease of use. With a device according to the present invention a locking member is provided to hold the cubes of chalk within the intended area for same with the locking member adapted for receipt of a special tool for installation and removal to hamper and minimize chalk removal by players.

The present invention relates to an improved device for holding and presenting a plurality of pieces or cubes of cue chalk around a pool or billiard table for use by players in order to properly apply chalk to the tip of a pool cue.
Historically, chalk for application to the tip of a pool cue is presented in a solid cube form with a paper covering about at least a majority of all but one side of the cube and with the exposed cube side having a preformed concavity therein for receipt of the tip of a pool cue. Rotation of the pool cue with the tip in contact with the concave chalk imparts a thin coating of chalk onto the cue tip to enhance contact between the cue tip and a cue ball. The concavity is preformed into the cube of chalk form to ensure the proper application of chalk to the full surface of the cue tip from first use of the chalk until the chalk is totally consumed, with the concavity becoming deeper and deeper into the cubic body of the chalk with continued use.
Individual cubes of chalk have been normally placed about a pool or billiard table, simply resting on the table rail or some nearby surface such that a player desiring to chalk his cue can simply hold the chalk in one hand and the cue in the other hand, insert the tip of the cue into the concavity of the chalk and create relative rotational movement so as to apply the chalk to the tip of the cue. In instances where individual cubes of chalk are unattached and freely reside around the pool table, a number of potential problems and/or inconveniences exist. First, a player may inadvertently place the cube of chalk in his pocket during play, and after completion of play may walk away with the chalk thus necessitating the operator to supply a new cube of chalk. Secondly, since the chalk freely rests on the rail of the pool table, it can be knocked onto the table and interfere with play or knocked onto the floor where it may be stepped on and broken, thus destroying the chalk as well as marking up the floor, carpet, or other floor covering.
Also, many pool tables, particularly in commercial establishments include a ball return trackway leading from the various ball pockets to a central location at one end of the table to facilitate return of the balls for retrieval and/or reracking for a new game. Frequently individual cubes of chalk will be knocked from their resting place on the rail of the pool table into one of the six pockets around the table. While each of the trackways for returning the balls to a common location is provided with a space to permit the chalk to fall through the trackway, often the chalk becomes lodged in the trackway and interferes with return of the balls. When such an occurrence happens, it becomes necessary for the table operator or the owner of the establishment to gain access to the trackway and remove the chalk, thus permitting free return of the balls that were held by the chalk. Otherwise, play on the table will have to be suspended. Since many pool tables located in commercial establishments are serviced by amusement companies located away from the commercial establishment, an extra service call is routinely necessary which causes the operator to send a service man to the location for removal of chalk. Though the removal process is simple, obviously time is required for the operator to make the service call and until the chalk is removed, play on the table must be suspended thus interfering with the pleasure and amusement of the players as well as causing lost income to the owner of the establishment.
A number of attempts have previously been made to provide a holder for chalk which would alleviate or reduce at least certain of the problems noted above. Such prior efforts are exemplified in the prior art listed below.
Ellul, Jr., U.S. Pat. No. 4,826,163 provides an elongated tubular structure having circular openings at opposite ends of same. Cubes of chalk are located within the tubular structure and with the formed concavity of the chalk being exposed behind the circular end openings. The device is secured to a support surface with access to the chalk through opposite ends of the device.
The Smith, Jr., U.S. Pat. No. 4,151,992 patent presents a housing behind which two pieces of chalk are presented and with circular openings therethrough for access by the cue tip to the chalk. A key lock is located between the two openings for removal of the housing cover for replacement of expended chalk and the introduction of new cubes. A base plate to which the housing cover is affixed is secured to a support surface.
Peterson, U.S. Pat. No. 1,627,573 includes a tubular element for receipt of a cube of chalk behind a circular opening and with a spring bias behind the chalk to maintain same immediately adjacent the opening. The tube is angularly adjustable with respect to a mounting plate for securing same to a surface.
Nelson, U.S. Pat. No. 1,571,211 discloses a support structure for receiving two pieces of chalk exposed at opposite ends and with rotary means associated therewith for imparting rotation to the chalk for application of the chalk to a cue tip.
Hill, U.S. Pat. No. 1,450,741 discloses a circular container for receiving chalk behind a circular opening and with a special key for removal of the cover from the chalk.
Moore, U.S. Pat. No. 1,194,212 shows a device for receiving a single cube of chalk and for securing same beneath the rail of a pool table so as to protrude angularly outwardly therefrom. The cube of chalk is secured within its housing with the end of same having the formed concavity being totally exposed for receipt of a cue tip.
Vasbinder, U.S. Pat. No. 1,031,668 is directed to an automatic chalking device where a cube of chalk held within a housing is automatically rotated by a spring mechanism for application of chalk to the cue.
Peloquin, U.S. Pat. No. 1,016,953 shows a chalk holder for mounting beneath the side rails of a pool table and for presenting a single cube of chalk behind a circular opening.
Jay, U.S. Pat. No. 974,066 shows a covered housing for receipt of a single cube of chalk and with a spring ratchet arrangement coupled with a spiral shaft for imparting rotation to the chalk for automatic chalking.
Wright, U.S. Pat. No. 789,779 shows a rectangular housing for receiving chalk therein and with openings at the ends of the housing exposing chalk to a cue tip. A special lock is provided to prevent removal of the chalk from the housing except by one with authority to do so.
Zaehringer, U.S. Pat. No. 334,099 discloses a housing for a cube of chalk which is located behind a circular opening with a housing that is mountable beneath a pool table.
While each of the above prior art patents discloses some technique for holding a piece of cue chalk and presenting same to a player for application of the chalk to the tip of a pool cue, such patents do not anticipate or suggest the structure of the improved device according to the present invention.

Device for holding chalk for application to tips of pool cues


A method and system for printing content from a computing device is provided. Content from the computing device is converted to a device independent format and printed in the device independent format. The content is converted using a mark-up language, which also defines the style of the content. The converted content description format is preloaded in the computing device and is provided to the printing device. The mark-up language may be XML and the description format may be in the is in the extensible Style sheet language (“XSL”) or extensible Style sheet language Transformation (“XSLT”) format.

1. Field of the Invention
This invention relates to device drivers, and more particularly to a format independent system that can be used by computing devices for printing.
2. Background
Portable computing devices including personal digital assistants ("PDAs"), mobile phones and other similar computing devices ("collectively referred to herein as "handheld devices") are widespread in today's business and personal lives. Most handheld devices generally store important business and/or personal information, e.g., address books, daily planners, memo-pads, calendars, project lists, and/or expense reports etc. A typical handheld device has limited computing power and low memory storage space for storing content.
One who uses a handheld device, generally carries it from place to place. Often, a handheld device user needs to print stored content from the handheld device. Generally, in order to print from a computing device, an application issues a user prompted print command to print content. A printer driver is required to facilitate the transfer of print data from the computing device to a printing device (hereinafter referred to as a "printer" or "printers").
One technique commonly used by applications (e.g. Microsoft Outlook, Microsoft Corporation®) is called "spooling". The application from which content is to be printed is spooled as a "spool file" on a storage media. The operating system (OS) spools up all the calls that the application makes to the printer driver and saves the calls in a spool file along with a copy of the print content. Then the spooled file with the print content is read from the storage media and handed to the printer driver. The printer driver takes the spooled file and creates a high level Printer Description Language File ("PDL file") and stores the PDL file on the storage media. The PDL file is then sent to the printer engine of the printer, and printed.
One example of the foregoing printer driver system is shown in FIG. 1. Based on user input, Application 100 converts the desired print content into graphical device interface ("GDI") format 101 or other text commands and graphics primitives. The print job may be spooled to a spool file 102, which is stored on a storage media (not shown). These commands may be formatted by printer driver 105 into a recognizable industry defined data definition (e.g. PCL), or to a device specific format, to create print commands 103 to control printer 104. Print commands 103 are sent to printer 104 with print content from spool file 102, which is then printed. Printer 104 may not be physically attached to a computing device where application 100 and printer driver 105 reside, but may be remotely located such as on a LAN network (not shown).
Most computing devices require device specific printer drivers, so that computer applications can interface with printer drivers and print content. Printer drivers in general require large memory space for storage. This becomes a problem for handheld devices because such devices have limited memory storage space. Also, since most printers require a specific printer driver, printing from a handheld device becomes very difficult because the handheld device may not be able to store multiple printer drivers.
Therefore, there is a need for a system that allows a handheld device to print data at any printer using a standard device independent format.


The present invention is directed to a procedure for making an enantiomerically enriched compound containing a hydronaphthalene ring structure. The process involves reacting oxabenzonorbornadienes with nucleophiles using rhodium as a catalyst and in the presence of a phosphine ligand. The compounds synthesized may be used in pharmaceutical preparations for the treatment of a variety of diseases and conditions.

The hydronaphthalene structure can be found in many natural products and pharmaceutical agents. These include homochelidonine (structure I below; Slavik, J.; et al., Collect. Czech. Chem. Commun. 30:3697 (1965); Spath, E., et al., Ber., 64:1123 (1931); Bersch, H. W., Arch. Pharm. (Weinheim, Ger.), 2914:91 (1958)) an alkaloid isolated from Chelidonium plants, dihydrexidine (structure 2 below; Snyder, S. E., J. Med. Chem., 38:2395 (1995)) which shows antiparkinsonian character, etoposide (structure 3 below; Kamal, A., et al., Tetrahedron Lett. 37:3359 (1996)) which is used in the treatment of various cancers, and SF-2315B (structure 4 below; Kim, K., et al., J. Org. Chem. 60:6866 (1995)) which is a viral reverse transcriptase inhibitor. In addition., CNS agents, immunoregulatory agents and antibiotics contain variations on this framework (Perrone. R., et al., J. Med. Chem. 38:942 (1995)).

Given the large number of pharmaceutically useful compounds which contain this core skeleton, new methodology which produces functionalized hydronaphthalene skeletons (structure 1) would clearly be of value.

Previous work on oxabicyclic ring opening reactions led to a catalytic enantioselective route to dihydronaphthol (Lautens, M., et al., Tetrahedron 54:1107 (1998)) which was a key step in the total synthesis of sertraline (Lautens, M., et al., J. Org. Chem. 63:5276 (1997)). However, little is known about the ring opening of oxabenzonorbornadiene or similar compounds with the incorporation of nucleophiles during the ring opening step. Duan and Chen developed a method of introducing aryl groups by using catalytic amounts of palladium (Duan, J.-P., et al., Tetrahedron Lett., 34:4019 (1993); Duan, J.-P., et al., Organometallics 14:1608 (1995)). Moinet et al., later developed an enantioselective version of this reaction but the yields were low (Tetrahedron Lett., 36:2051 (1995)).
Catalytic organometallic processes that form carbon-heteroatom bonds are far fewer in number than those which form carbon-carbon bonds. The Wacker Process (Henry, P. M., Paladium Catalysed Oxidation of Hydrocarbons, vol. 2, Reidel, Boston, (1980)), oxidative carbonylations of amines and alcohols (Applied Homogeneous Catalysis with Oranometallic Compounds: A Comprehensive Handbook in Two Volumes (eds.: B. Cornils, W. A. Herrmann), VCH, New York, (1984)) and the formation of arylamines and aryl ethers (Hartwig, J. F., Agnew. Chem. Int. Ed. 37:2046 (1998); Widenhoefer, R. A., et al., J. Am. Chem. Soc. 119:6787 (1997)) are a few that have been described to date.

Compounds and a novel process for their preparation


The disclosure provides a sensor and method for the measurement of fluid properties, such as steam energy and steam quality, and/or multiphase and multicomponent fluids and their flow regime profiles in a single instrument, and in some embodiments can include the mass flow rate. The invention can incorporate an orifice function that permits the measurement of fluid energy and a flow profile across at least a portion of the flow path with an electromagnetic sensing method combined with a standard mass flow rate measurement using an orifice differential pressure measurement system.

Field of the Invention
The disclosure relates generally to a system and method for measurement of the discernible properties of a fluid that relate to the composition of a fluid and the energy content of a fluid, such as steam, including a fluid attribute such as steam quality. More specifically, the disclosure relates to a system and method for measurement of the quality and related energy and composition properties of a fluid, such as steam, using electromagnetic waves.
Description of the Related Art
Fluid properties depend upon molecular composition, fluid phase and fluid internal energy state. The energy state for a given fluid phase can generally be described in terms of temperature and pressure. For example, steam energy is mainly composed of thermal energy as in heat and kinetic energy as in movement of atoms and molecules. Besides temperature and pressure as exemplary parameters for steam energy, another parameter for steam energy, which quantifies its composition with respect to phase, is steam quality. Steam quality quantifies the amount of condensed water present in saturated steam. Specifically, steam quality is defined as the mass ratio of saturated steam vapor to the total vapor plus condensate in a steam vapor- and liquid-water mixture. Although quality is an important process variable, it is not one that is easily measured in real-time. A standard method for measuring steam quality involves expensive and complicated calorimeter devices, as well as considerable time and effort. As a result, timely measurements of quality are often not available. Another standard method used in industrial settings is to measure the temperature and pressure at given points in a process flow and correlate those measurements to a database to predict the steam quality without actually measuring the quality. In the first method, the ability and time may not be available, such as in many industrial processes. In the second method that may be used for industrial processes, the accuracy may be insufficient. For example, steam turbines are operated typically at less than optimum efficiency to allow a margin of error for inaccuracies in steam quality and avoid large-scale damage. An example of such operation is described in U.S. Pat. No. 8,433,526 B2, entitled "Method and System for Steam Quality Monitoring", where the Abstract states:                A method of determining a steam quality of a wet steam located in an interior of a steam turbine includes emitting from an optical probe a plurality of wavelengths through the wet steam, measuring with the optical probe a wet steam intensity corresponding to each of the plurality of wavelengths emitted through the wet steam, determining an intensity ratio vector by dividing the wet steam intensity by a corresponding dry steam intensity for each of the plurality of wavelengths, successively applying scaling factors to the intensity ratio vector to obtain a scaled intensity ratio vector, calculating a suitable value for each of the scaling factors to obtain a plurality of residuals, determining a minimum residual of the plurality of residuals, determining a droplet size distribution by calculating the droplet number density corresponding to the minimum residual, and determining the steam quality based on the droplet size distribution.
It is well known that electromagnetic ("EM") energy can be applied to materials and the resulting response comprising energy passing through or reflected from the material can be measured to indicate properties of the materials. Electromagnetic properties of materials are frequency dependent. Information about the composition of the substance can be obtained by exposing the substance to EM energy at different frequencies and analyzing the response as a function of frequency. The term "permittivity" describes how a material responds to an applied electric field. Permittivity is determined by the ability of a material to polarize in response to an externally applied field so as to reduce the total electric field inside the material. Permittivity is often expressed as a relative value which is the ratio of the complex permittivity to the permittivity ε0 of a vacuum. The response of natural materials to external EM fields depends on the frequency of the field, because the material's polarization does not respond instantaneously to an applied field. Permittivity for materials is expressed as a complex function to allow specification of the energy storage property and energy dissipation property of the material as a function of the angular frequency (ω) of the applied field by means of real and imaginary components, respectively, as follows:εr(ω)=εr′(ω)−jεr″(ω)
Magnetic permeability, as another form of a material's response to applied EM energy, can be compared with electrical permittivity in that it is the degree of magnetization of material from reordered magnetic dipoles in the material when responding to a magnetic field applied to the material. Magnetic permeability is often expressed as a relative permeability to permeability μ0 in a vacuum. Magnetic permeability is also frequency dependent and can include real and imaginary components.
The dielectric properties of water have been measured and vary considerably based on the thermodynamic state of the water. At 100° C., the real part of the static relative permittivity of water changes from approximately 56 for the liquid phase to approximately 1.012 as a gas. However, the typical range in the permittivity values seen for a mixture of water and steam is much less than the large difference in the permittivities of liquid and vapor. This reduction in sensitivity is due to the fact that the permittivity of a mixture of molecules depends upon the relative volume occupied by each constituent. As a result, the permittivity of steam varies only from about 1.012 for dry steam to about 1.08 for 50% (x=0.5) steam quality at 100° C. and 175 psia. As temperature increases, the permittivities of both dry steam and water decrease. Increasing pressure typically increases the permittivity value.
There exists a significant need for a low cost, accurate, and robust sensing method and corresponding commercially viable instrument to measure fluid properties, including the energy of steam and related steam quality and other fluid parameters such as composition, using EM energy in a number of important energy production and industrial processing applications.

Electromagnetic steam energy/quality, flow, and fluid property sensor and method


A support bracket for a disk brake of the type having a floating caliper comprises securing means for securing the support bracket to the suspension of a vehicle, and support means suitable for slidably supporting a sliding caliper body. The support bracket comprises an inner wall facing the inside of the vehicle and an outer wall opposite the inner wall and spaced therefrom. The inner wall and the outer wall are fixedly joined and arranged one on each side of a disk plane and delimit a space for accommodating a portion of a brake disk. Each of the inner wall and the outer wall forms two pad seats for accommodating pads.

The present invention relates to a disk brake, particularly for high performance motor vehicles, of the type comprising a support bracket having opposing walls provided with seats for accommodating respective pads, and a sliding caliper body provided with seats for accommodating hydraulic pistons for urging the pads against one another.
As is known, disk brakes of the type specified, while being satisfactory for use in medium performance vehicles with brake disks of modest dimensions, have considerable disadvantages for use in heavy, high performance vehicles which require high braking performance. High performance vehicles, in order to have available an adequate braking power, require the use of brake disks and pads having large dimensions. This involves an increase in the dimensions of the support bracket and also of the caliper body and, consequently, an increase in the lever arms which, together with the high braking force, give rise to excessive stresses on and deformation of the brake. In addition, an increase in the dimensions of the pads and an increase in the braking force involve the problem of non-uniform wear on the pads and the problem of dimensioning and positioning the hydraulic thrust units. In order to ensure reliable operation, the individual components of the brake, in particular the slideways of the sliding caliper body, have to be over-dimensioned, which involves increased production costs.


An arrangement for connecting an electronic subassembly and an optical subassembly in an electro-optical communication device such as an electro-optical transceiver. The arrangement includes a body of a rigid dielectric material for mounting e.g. on the optical subassembly. The body has electrically conductive pathways provided thereon and includes a shaped portion providing a socket-like formation. At least one electrical contact element is coupled with e.g. the electronic subassembly. The electrical contact element is pluggable into the socket-like formation of the body of rigid dielectric material and includes an elastic device adapted to elastically co-operate with the socket-like formation of the body of rigid dielectric material to retain the electrical contact element plugged in the socket-like formation to provide electrical contact with the electrically conductive pathways provide thereon, while permitting vibrational displacement of the electrical contact element within the socket-like formation.

1. Field of the Disclosure
The present disclosure relates to connection arrangements for optical communications.
The disclosure was developed with specific attention paid to the possible use in connecting Optical Sub Assemblies (OSA's) and Electronic Sub Assemblies (ESA's) in optical communication devices such as e.g. transceivers for optical communications.
2. Discussion of the Background Art
Electro-optical communication devices such as transceivers for optical communications typically comprise an Electronic Sub Assembly (ESA) and an Optical Sub Assembly (OSA) in a single package. Such an arrangement is schematically illustrated in FIG. 1, where a carrier body 100, typically of a metal material, is shown having mounted thereon an Electronic Sub Assembly (ESA) 102 and an Optical Sub Assembly (OSA) 104. The Electronic Sub Assembly 102 is e.g. in the form of a small printed circuit board (PCB) 106 having electronic circuitry 108 mounted thereon. The Optical Sub Assembly 104 is typically in the form of a casing or enclosure mounted at the "distal" end 110 of the carrier body or package 100 of the transceiver where the optical components of the transceiver i.e. the laser diode (transmitter) and the photodetector (receiver) are arranged in view of connection to the optical link fibre(s).
A current trend in recent years is to make transceivers pluggable, possibly in the form of "hot" pluggable units, that is units that can be plugged/unplugged in a host system without powering-off the host system. Such an arrangement is exemplified in FIG. 1. There, the ESA illustrated is provided at its "proximal" end with slidable electrical contacts 112 that enable plugging/unplugging the transceiver in a sort of socket (not shown) provided in the rack where the transceiver is mounted.
Proper and effective connection between the OSA and the ESA is a critical issue in manufacturing optical transceivers, especially when operating rates of the order of 10 Gbit/s and higher are contemplated.
In the first place, the connection must be as short as possible in order to guarantee high data rates. Additionally, the connection should be not too rigid in order to avoid damages due to shocks or vibrations.
Assembling the OSA and the ESA in the transceiver package should be a simple, reliable process. The ESA and the OSA are tested separately (in order to circumvent yield problems related to malfunctioning of only one of the subassemblies) and then connected. After being assembled and connected, the ESA and the OSA are tested again in order to extract and verify the programming parameters and the functionality of the complete transceiver.
Assembling the OSA and the ESA is usually performed manually or by resorting to automated, dedicated soldering process that inevitably tend to be quite expensive.
FIG. 2 is an enlarged view of the portion of FIG. 1 indicated by arrow II and includes a portion M magnified for the sake of clarity of illustration. FIG. 2 is exemplary of conventional solutions where the connection of the OSA and the ESA is produced by (hand) soldering brazed leads of the OSA directly onto soldering pads carried by the ESA.
Specifically, the left-hand portion of FIG. 2 illustrates some of the components typically located within the OSA casing. By referring, by way of example, to the transmitter side, these include a laser diode 114 having associated focusing optics in the form of e.g. a "ball" lens 116. The laser source 114 is mounted onto a thermal conditioning element 118 such as a Peltier element.
While the transmitter side of the OSA is considered here by way of example, a substantially similar layout can be considered for the receiver side—insofar as the points of momentum for the disclosure are concerned. Additionally, while a transceiver is being primarily referred to, this description will almost identically apply to electro-optical communication devices including only a transmitter or a receiver.
As used herein, the wording "electro-optical communication device" is thus inclusive of any of an optical transmitter, an optical receiver and an optical transmitter/receiver (i.e. a "transceiver").
The reference numeral 120 designates as a whole a "feedthrough", namely a shaped body of a rigid material as required for high data rate operation—such as e.g. ceramics or glass that creates (via electrical conductive stripes provided thereon) electrical pathways through the OSA casing. Specifically, in the exemplary arrangement illustrated in FIG. 2, the feedthrough 120 is shown having a sort of pod-like formation 122 protruding from the OSA casing wall. One or more electrical leads 124 brazed on the upper side of the formation 122 extend from the OSA feedthrough 120 to be soldered to corresponding conductive pads (not visible) on the ESA thus ensuring electrical connection between the OSA and the ESA. Alternative prior art solutions may include, in the place of the lead or leads 124, a flexible printed circuit board, known also as a "flex".
However effective, the prior art solutions discussed in the foregoing are costly and entail a number of disadvantages. In appreciating these negative factors, one must take into account the fact that the elements involved are generally very small: for instance, the ceramics/glass body comprising the feedthrough 120 may have a height and a length (as observed in FIG. 2) smaller than 5 mm, typically 3 mm or less.
On that size scale, leads such as the leads 124 may turn out to be too rigid, and measures have to be taken in order to improve resistance against shocks and vibrations. This requires design efforts, expensive profiling fixtures and making the leads longer than strictly required for connection purposes. However, longer leads included in the RF portion of the transceiver militate against high data throughput.
Using a "flex" (i.e. a flexible printed circuit board) somehow palliates the problems related to shock resistance. Unfortunately, using a flex renders the assembly process rather complicated, this being particularly the case if an automated production environment is considered. Additionally, in those optical communication devices where a very limited space is available, such as e.g. Small Form Factor Pluggable (SFP) transceivers, using a short flex is practically mandatory, and such a short flex tends to be as rigid as a fixed lead.
A particularly penalising feature of prior art arrangements as illustrated in FIG. 2 lies in that these arrangements involve a steady (i.e. non-releasable) connection between the OSA and the ESA e.g. by soldering. In the case of malfunctioning of either subassembly, the transceiver as a whole is usually disposed of: in fact, separating the malfunctioning subassembly from the subassembly that operates correctly, removing the malfunctioning subassembly from the transceiver, substituting a replacement unit for the malfunctioning subassembly removed and re-establishing the mechanical and electrical connections between the OSA and the ESA is an expensive and time-consuming process, and may also give rise to problems in terms of reliability. In turn, the OSA and ESA are both rather expensive components, and dispensing with transceiver—as a whole—because only one of the ESA and the OSA is malfunctioning is hardly an acceptable choice from the economical viewpoint.
The object of the present disclosure is thus to provide an arrangement that overcomes the drawbacks intrinsic to the prior arrangements considered in the foregoing.

Connection arrangement and method for optical communications

Avago Technologies General IP (Singapore) Pte. Ltd.