A method of depositing diamond-like films produces depositing species from a plasma of a hydrocarbon gas precurser. The plasma is generated by a laser pulse which is fired into the gas and is absorbed in an initiater mixed with the gas. The resulting detonation produces a plasma of ions, radicals, molecular fragments and electrons which is propelled by the detonation pressure wave to a substrate and deposited thereon.

Diamond-like coatings are in great demand as protective coatings for optical components; as coatings in sliding wear parts such as valves, pistons, bearings and the like; as heat sinking materials in integrated circuit technology and as laser host material. Diamond-like coatings also have great potential as a integrated circuit semi-conductor material because of the very high heat transfer of such materials. By diamond-like coatings, applicant means coatings formed of carbonaceous species having characteristics of hardness and chemical structure similar to natural diamond, at least in part. Such coatings may include other species of chemicals and structure, at least in part.
Because of the great demand for these materials, techniques have been developed to produce this material. Common to all of the production techniques is the formation of a gas plasma as a source of free radicals and ions which form the depositing species and/or coating environment and which provides the transient energy required for diamond or diamond-like film nucleation. The conventional methods require radio frequency electronics to generate the plasma and require suitable filtering and collimating electrodes to extract and control the depositing species.
In addition, conventional methods require the provision of a means for insuring an electrical potential difference between the plasma region and the substrate to be coated, normally in the range of 100 to 1,000 electron volts potential difference. A further problem common to conventional methods of formation of diamond-like coatings is the requirement that adequate cooling be provided for the substrate, since the substrate is in close proximity to a very hot plasma. Conventional processes require that the substrate be maintained near room temperature as a key ingredient to forming diamond-like coatings. Heating of the coating films, either during formation or afterwards, will collapse the sp3 bonding characteristic of diamond films to a sp2 bonding, that is, will convert the diamond-like film to one of graphite.
Diamond-like coatings formed by state of the art methods notoriously have problems with adhesion to the substrate and are unable to support a shear stress. The industry recognizes a ten micron thickness limit as that which is attainable by conventional processes. The accumulation of diamond-like material above this limit incurs problems with the cohesive forces within the film which induces delamination of the film. Moreover, attempts to produce film beyond the ten micron thickness result in the collapsing of the sp3 hybrid to the sp2 bonding, that is, the formation of graphite. These films, above the ten micron thickness, have a very weak bond to the substrate such that the diamond-like coating can be easily scraped from the substrate, for example by application of a dental pick.
Conventional plasma assisted techniques for producing diamond-like coatings grow coatings which have separate, granular crystal structure, that is, an irregular geode-like appearance on microscopic examination. These films of discrete crystaline nature are unsatisfactory particularily when used as optical coatings since scattering of light as a result of the separate crystals can degrade the optical throughput.
With this process, continuous, tightly adhering, optically suitable diamond-like films may be deposited on substrates such as lenses, or on other surfaces subject to wear, without the use of the electronics and necessary in state of the art deposition processes. This method generates a plasma by the absorbtion of laser radiation into a precurser gas or gas mixture. The gas rapidly decomposes to produce the accelerating forces and the depositing species necessary to produce diamond-like coatings. Externally generated accelerating fields or potentials between the gas and the substrate are not required. Moreover, it is not necessary to substantially heat the substrate prior to deposition. Instead, the plasma region may be spaced from the substrate and generated intermittently, for example at ten microseconds duration, so that the temperature excursions are transient and high energies are developed to propel the deposition species onto the substrate. This system does not require a sophisticated vacuum system, as do conventional methods, since the coatings may be produced at atmospheric pressure as well as at reduced pressured. For example, applicant's process may typically operate at one to 100 torr total pressure. Conventional deposition processes normally take place at millitorr pressures.
This process may also work to provide deposition coverage of substantially greater areas than previous techniques. Previously, the art required collimated beams or very localized plasma mixtures which result in small area coverage. This process may be used over much wider areas. Moreover these films may be much thicker than conventional films. This process has produced films of greater than ten microns thickness. At this thickness the films have very high adhesion to the substrate. Standard pull tests indicate that the films may withstand in excess of 10,000 psi pulling pressure. The films are also very strong in shear stress. A Sebastian pulling post can be pulled through twenty degrees on removal of this film.
In addition to coating flat substrates, this process may produce coatings over curved or irregular surfaces as well. Coated surfaces of this type would be highly valuable on curved lenses, on nosecones, aircraft canopies and on windows. The films have a high degree of lubricity as well as hardness and durability.
It is an object of this invention to produce tightly adhering diamond-like coatings on substrates and to produce substrates having the diamond-like coatings thereon.
It is a further object of this invention to produce diamond-like coatings having superior optical, electrical, electronic, thermal and mechanical properties.
It is also an object of this invention to produce diamond-like coatings from a laser induced plasma and to develop a method for producing such coatings.
It is an object of this invention to develop a method of producing diamond-like coatings by absorbing laser produced energy into a coating precurser gas.
It is an object of this invention to develop a method of producing diamond-like coatings by absorbing laser energy into a plasma initiator.
It is an object of this invention to develop a method of producing diamond-like coatings from a precursor gas by initiating and propagating a laser induced plasma therein.
These and other objects will be apparent from the following Description of the Drawings and Description of the Preferred Embodiments.

Diamond like coating and method of forming


The touch screen panel of the present invention includes first sensing patterns formed on a transparent substrate, a first insulating film formed on the first sensing patterns, second sensing patterns formed on the first insulating film, a plurality of metal patterns disposed on edge regions of the first and second sensing patterns, and a plurality of auxiliary metal patterns formed in the same layer as the metal patterns. Each of the first and second sensing patterns has sensing cells and coupling lines. Each of the coupling lines connects two of the sensing cells. Each of the metal patterns is coupled to the first sensing pattern or to the second sensing pattern, and each of the auxiliary metal patterns being formed on one of the first coupling lines or on one of the second coupling lines.

1. Field of the Invention
The present invention relates to a touch screen panel, and more particularly, to a touch screen panel that minimizes resistance of an intersection portion of first and second sensing patterns.
2. Description of the Related Art
A touch screen panel is an input device through which a user can input his or her instruction by selecting an instructed content displayed on a screen such as an image display device, etc. using a human's finger or an object.
To this end, the touch screen panel is provided on the front face of the image display device to convert a contact position, which the human's finger or object directly contacts, into an electrical signal. Therefore, the instructed content selected on the contact position is accepted as an input signal.
The touch screen panel as described above can replace an input device, e.g., a keyboard, a mouse, or the like to be coupled to the image display device to operate so that its applications are expanding widely.
As a method to implement the touch screen panel, a resistive type, a photosensitive type and an electrostatic capacity type have been known.
Among others, the electrostatic capacity type touch screen panel includes a conductive sensing pattern to sense change in electrostatic capacity formed in association with other sensing patterns in the vicinity thereof or a ground electrode, etc., thereby converting a contact position into an electrical signal.
Here, in order to clearly determine the contact position on the contact surface, the sensing pattern includes first sensing patterns (X patterns) formed to be coupled along a first direction, and second sensing patterns (Y patterns) formed to be coupled along a second direction.
The first and second sensing patterns as described above are generally positioned in the same layer. In this case, the sensing patterns positioned in the same X or Y lines are coupled by forming separate coupling patterns through contact holes formed in insulating films there.
Here, since the coupling patterns are made of the same material as the first and second sensing patterns, a mask process should be added in order to form the coupling patterns, thereby causing problems that the number of masks is increased and the process is complicated.
Also, if the first or second sensing patterns are electrically coupled through the separate coupling patterns, the first sensing pattern and the second sensing patterns are intersected with each other in regions where the coupling patterns are formed.
At this time, the width of the coupling pattern is generally minimized in order to reduce the effect of parasitic capacitance generated by the coupling pattern. When the coupling pattern has a narrow width, conversely, line resistance becomes high to have a disadvantage that sensing sensitivity is lowered.


The invention relates to microfluidic devices and methods that employ electromagnetic radiation to move a droplet of fluid on a fluid-transporting surface of a substrate. Typically, radiation of a particular wavelength is directed through a substantially transparent material, and the radiation imparts an optical trapping force to move the droplet. In addition, a means for reducing evaporative loss from the droplet may be provided.

The present invention relates to the use of electromagnetic radiation to move droplets of fluid on a fluid-transporting surface. In particular, the invention relates to microfluidic devices and methods in which radiation is directed through a material that is substantially transparent to that radiation in order to optically move fluid droplets on a fluid-transporting surface. Typically, optical movement of fluid droplets is achieved while evaporative loss from the droplets is reduced.
A number of factors have contributed to the recent advances in the fields of biological sciences, biochemical assays, clinical diagnostics, and synthetic and analytical chemistry. These factors, for example, include the growing significance of genomics, the emergence of proteomics, and developments in combinatorial chemistry. In addition, the rise of drug-resistant forms of infectious diseases, increases in the incidence of food-chain contamination by pathogenic bacteria, the threat of biological warfare, and the continued prevalence of infectious diseases in underdeveloped countries also highlight the need for improved techniques for drug screening, drug target validation, toxicology studies, and combinatorial chemistry.
In these fields, progress has often been limited by the inability to process large numbers of samples at high speed. Extended time frames are necessitated by tedious sample preparation techniques and slow detection methods. These constraints in turn make automation of diagnostic assays difficult and create barriers to driving assay costs down. Thus, there is a current need in the art for rapid and inexpensive techniques to carry out diagnostics, parallel syntheses, and high throughput screening.
Expensive or rare fluids are employed in many emerging scientific applications, such as proteomics and genomics. Thus, considerable interest has been focused on microfluidic techniques, which typically involve small sample volumes and low reagent consumption. In addition, microfluidic techniques may be used to carry out numerous parallel processes, can be used across a range of fluid properties, and are compatible with movement of biological moieties that may vary by orders of magnitude in size and physical characteristics (e.g., from peptide hormones to intact cells). Processes in a microfluidic format are, therefore, particularly amenable to automation, enabling routine screening and surveillance programs to be established. In addition, new process paradigms, such as flow-through processing of biological samples, become feasible only in a microfluidic format.
A variety of microfluidic devices have been developed for chemical and bioanalytical applications. Typically, microfluidic devices involve the miniaturization and automation of a number of laboratory processes, which are then integrated on a chip. Thus, microfluidic technology may be employed to carry out a series of chemical or biochemical processes in a single device, including sample purification, separation, and detection of specific analytes. Applications include medical diagnostics, genetic analysis, or environmental sampling. See, e.g., Ramsey et al. (1995) xe2x80x9cMicrofabricated chemical measurement systems,xe2x80x9d Nat. Med. 1:1093-1096.
Microfluidic devices may be constructed using simple manufacturing techniques and are generally inexpensive to produce. For example, the microfabrication methods used to make microchips in the computer industry may also be used to create microfluidic devices, enabling the creation of intricate, minute patterns of interconnected channels. Once a pattern is created, microchip manufacturing methods are employed to recreate the channel design in a substrate. In some instances, chemical etching or stamping techniques are employed. As a result, highly precise channels with dimensions that can be varied in their width and depth may be produced on a substrate. Once the pattern is produced in the substrate, a cover plate is affixed over the substrate so as to form conduits in combination with the channels.
Typically, the substrates and/or cover plates are comprised of a rigid material such as glass (see, e.g., Woolley et al. (1994), xe2x80x9cUltra-high-speed DNA fragment separations using microfabricated capillary array electrophoresis chips,xe2x80x9d Proc. Natl. Acad. Sci. USA 91:11348-11352), plastic (see, e.g., McCormick et al. (1997), xe2x80x9cMicrochannel electrophoretic separations of DNA in injection-molded plastic substrates,xe2x80x9d Anal. Chem. 69:2626-2630), silicon, or quartz. Alternatively, microfabricated elastomeric valve and pump systems have been proposed in International Patent Publication No. WO01/01025. Similar valves and pumps are also described in Unger et al. (2000) xe2x80x9cMonolithic microfabricated valves and pumps by multilayer soft lithography,xe2x80x9d Science 288:113-116. These publications describe soft lithography as an alternative to silicon-based micromachining as a means by which to form microfluidic devices. Through soft lithography, microfluidic structures created entirely from an elastomer may be constructed containing on/off valves, switching valves, and pumps.
The above-described microfluidic devices, however, pose certain technical challenges that must be overcome. For example, fluid flow characteristics within the small flow channels of a microfluidic device may differ from the flow characteristics of fluids in larger devices, since surface effects tend to predominate, and regions of bulk flow become proportionately smaller. Consequently, several techniques have been developed in order to achieve fluid flow control in microfluidic devices. One commonly used technique involves the generation of electric fields to manipulate buffered, conductive fluids around networks of channels through electrophoretic or electroosmotic forces. See, e.g., Culbertson et al. (2000), xe2x80x9cElectroosmotically induced hydraulic pumping on microchips: differential ion transport,xe2x80x9d Anal. Chem. 72:2285-2291. Another technique, as described in Anderson et al. (2000), xe2x80x9cA miniature integrated device for automated multistep genetic assays,xe2x80x9d Nucleic Acids Res. 28:E60, involves achieving fluidic control by coupling the device to an external system of solenoid valves and pressure sources.
The use of three-dimensional channels to define fluidic pathways, however, gives rise to several limitations. For example, leakage of fluids or analytes into undesired channels through diffusion or the influence of local electric field gradients requires the precise control of bias voltages along each channel in the microfluidic network. This need for precise control increases the design constraints for complex systems and requires that a high degree of engineering sophistication be incorporated into the microfabricated device. In particular, electric field gradients and path length differences around bends or corners in fluidic channels will also distort the distribution of analytes within the sample stream. This distortion can degrade the performance of an electrophoretic separation. In addition, the infrastructure and circuitry required to establish the electric fields are associated with certain spatial requirements that limit the complexity of the microfluidic devices. Furthermore, microvalves and other fluid control mechanisms greatly increase the complexity, cost, and manufacturability of such highly integrated designs.
In some instances, electric fields may be applied to move fluids without the use of three-dimensional channels. For example, U.S. Pat. No. 6,294,063 to Becker et al. describes microfluidic devices that programmably manipulate packets of fluids through the application of electric fields via electrodes located on the devices. A fluid is introduced onto a reaction surface and compartmentalized to form a packet. An adjustable programmable manipulation force is applied to the packet according to the position of the packet. As a result, the packet is programmably moved according to the manipulation force. In some cases, electromagnetic radiation may be used to maintain photochemical reaction or for sensing processes.
An alternative technique uses electric fields to effect fluid movement without channels and relies on the ability of electric fields to change the contact angle of a fluid on a surface (see, e.g., Lee et al. (2002), xe2x80x9cElectrowetting and electrowetting-on-dielectric for microscale liquid handling,xe2x80x9d Sensors and Actuators A 95:259-268). Upon application of an electric field gradient to a droplet on a fluid-transporting surface, different contact angles are formed between leading and receding surfaces of the droplet with respect to the fluid-transporting surface. This imbalance in surface tension forces will produce a net force, and move the droplet. Other techniques have been explored for manipulating droplets of liquid on a substrate surface. For instance, Ichimura et al. (2000), xe2x80x9cLight-driven motion of liquids on a photoresponsive surface,xe2x80x9d Science 288:1624-1626, describes placing a macroscopic droplet upon a particular surface polymer layer on a substrate, and using ultraviolet or blue light to change the isomeric form of the polymer layer. As a result, the contact angle between the droplet and the surface is changed, thereby moving the droplet. This approach is currently incapable of moving fluids at speeds exceeding about 35 xcexcm/s, however, and it does not work with polar fluids.
Another technique involves the use of thermal gradients to move droplets of liquid. See, e.g., Kataoka et al. (1999), xe2x80x9cPatterning liquid flow on the microscopic scale,xe2x80x9d Nature 402:794-797. The application of thermal gradients generates a thermocapillary shear stress at the air-liquid interface that is capable of driving a droplet across a surface. By the patterning of channels onto a surface, fluid movement can be precisely controlled. Another thermal gradient-driven approach, as described in Daniel et al. (2001), xe2x80x9cFast droplet movements resulting from the phase change on a gradient surface,xe2x80x9d Science 291:633-636, uses droplet coalescence to obtain droplet speeds of over 1 m/s. In either of these cases, however, the application of heat may not be suitable for some aspects of biological assays, and may exacerbate evaporation problems.
Optical trapping is a widely exploited phenomenon for manipulating items such as atoms, molecules, and small particles. The fundamental principle behind optical trapping is that light carries momentum, which can then be expressed as radiation pressure. When light is absorbed, reflected, or refracted by a material, momentum is transferred to the material. Optical tweezers have been developed that controllably deliver radiation pressure to manipulate small particles. Exemplary applications of optical tweezer technology include the manipulation of biological particles, such as cells, bacteria, and viruses (see, e.g., U.S. Pat. No. 4,893,886 to Ashkin et al. and U.S. Pat. No. 6,067,859 to Kas et al.), and the immobilization of biomolecules such as DNA, RNA, proteins, lipids, carbohydrates, or hormones (see U.S. Pat. No. 6,139,831 to Shivashankar et al.). While U.S. Pat. No. 6,294,063 to Becker et al. alludes to the use of optical tweezer technology for microfluidic manipulation, the microfluidic devices described require electrodes in order to apply electric fields that move the droplets and/or sense the position of the droplets. Since electrodes are generally opaque and do not allow the transmission of light therethrough, the microfluidic devices described in Becker et al. are generally incompatible with optical tweezer technology. As a result, optical trapping has not been successfully implemented in the field of microfluidics.
Thus, there exist opportunities in the field of microfluidics to employ optical techniques in order to controllably move fluids on a substrate surface.
In a first embodiment, an optical microfluidic device is provided, comprising a solid substrate, an electromagnetic radiation source, and a means for directing electromagnetic radiation. The solid substrate has a fluid-transporting surface and an opposing electromagnetic radiation-receiving surface, and is comprised of a material that is substantially transparent to electromagnetic radiation of a particular wavelength. The electromagnetic radiation source serves to generate electromagnetic radiation having the particular wavelength. The means for directing electromagnetic radiation is adapted to direct radiation generated by the source toward the radiation-receiving surface of the substrate. As a result, the directed electromagnetic radiation is transmitted through the substrate to the fluid-transporting surface in a manner effective to optically move one or more droplets of a selected fluid on the fluid-transporting surface from a first site to a second site.
In another embodiment, the invention provides an optical microfluidic device as above, except that the solid substrate is not necessarily comprised of a substantially transparent material. In such a case, an optically homogeneous cover plate is provided, comprising a material that is substantially transparent to electromagnetic radiation of the particular wavelength. In addition, the cover plate has an electromagnetic radiation-receiving surface and an opposing surface that faces the fluid-transporting surface. Accordingly, the means for directing electromagnetic radiation is adapted to direct radiation generated by the source toward the radiation-receiving surface of the cover plate. The directed electromagnetic radiation is transmitted through the cover plate to the fluid-transporting surface of the substrate in a manner effective to optically move one or more droplets of a selected fluid on the fluid-transporting surface from a first site to a second site.
In another embodiment, the invention provides an optical microfluidic device as generally described above except that neither a substantially transparent substrate or cover plate is required. Instead, the inventive device is comprised of a substrate (transparent or opaque) having a fluid-transporting surface, an electromagnetic radiation source, and a means for reducing evaporative loss of any droplet or droplets on the fluid-transporting surface.
In yet another embodiment, a method is provided for controllably moving a droplet of a selected fluid across a surface of a solid substrate. A droplet of a selected fluid is deposited on a first site of a fluid-transporting surface of a solid substrate. The substrate is comprised of a material that is substantially transparent to electromagnetic radiation of a particular wavelength. Then, electromagnetic radiation having the particular wavelength is directed toward a radiation-receiving surface that opposes the fluid-transporting surface of the substrate. As a result, the directed radiation is transmitted through the substrate to the fluid-transporting surface in a manner effective to optically move the droplet to a second site on the fluid-transporting surface.
In a further embodiment, a method is provided for controllably moving a droplet of a selected fluid across a surface of a solid substrate as described above, except that the substrate may not be substantially transparent. Instead, an optically homogeneous cover plate is provided comprising a substantially transparent material and having an electromagnetic radiation-receiving surface and an opposing surface. The cover plate is placed over the fluid-transporting surface, such that the opposing surface faces the fluid-transporting surface. Then, electromagnetic radiation is directed toward the radiation-receiving surface and through the cover plate to the fluid-transporting surface in a manner effective to optically move the droplet to a second site on the fluid-transporting surface.
In a still further embodiment, the invention provides methods for controllably moving a droplet of a selected fluid across a surface of a solid substrate as described above, except that the method additionally involves reducing evaporative loss from the droplet while the droplet is on the fluid-transporting surface. In this embodiment, the substrate may or may not be substantially transparent to light of the particular wavelength.
In yet another embodiment, the invention provides a method for controllably moving a fluid droplet across an interior surface of an enclosure, wherein the enclosure is formed at least in part by an optically homogeneous solid wall comprised of a material that is substantially transparent to electromagnetic radiation of a particular wavelength. A droplet of a selected fluid is deposited on the interior surface of the enclosure at a first site. Then, electromagnetic radiation of the particular wavelength is directed through the solid wall in a manner effective to optically move the droplet across the interior surface to the second site.

Optical microfluidic devices and methods


The present invention is directed to small molecule inhibitors of the IgE response to allergens, which are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. This invention also relates to benzimidazole molecules that are cellular proliferation inhibitors and thus are useful as anticancer agents.

1. Field of the Invention
This invention relates to small molecule inhibitors of the IgE response to allergens that are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. This invention also relates to small molecules that are proliferation inhibitors and thus they are useful as anticancer agents.
2. Description of the Related Art
Allergies and Asthma
An estimated 10 million persons in the United States have asthma, about 5% of the population. The estimated cost of asthma in the United States exceeds $6 billion. About 25% of patients with asthma who seek emergency care require hospitalization, and the largest single direct medical expenditure for asthma has been inpatient hospital services (emergency care), at a cost of greater than $1.6 billion. The cost for prescription medications, which increased 54% between 1985 and 1990, was close behind at $1.1 billion (Kelly, Pharmacotherapy 12:13S-21S (1997)).
According to the National Ambulatory Medical Care Survey, asthma accounts for 1% of all ambulatory care visits, and the disease continues to be a significant cause of missed school days in children. Despite improved understanding of the disease process and better drugs, asthma morbidity and mortality continue to rise in this country and worldwide (U.S. Department of Health and Human Services; 1991, publication no. 91-3042). Thus, asthma constitutes a significant public health problem.
The pathophysiologic processes that attend the onset of an asthmatic episode can be broken down into essentially two phases, both marked by bronchoconstriction, that causes wheezing, chest tightness, and dyspnea. The first, early phase asthmatic response is triggered by allergens, irritants, or exercise. Allergens cross-link immunoglobulin E (IgE) molecules bound to receptors on mast cells, causing them to release a number of pre-formed inflammatory mediators, including histamine. Additional triggers include the osmotic changes in airway tissues following exercise or the inhalation of cold, dry air. The second, late phase response that follows is characterized by infiltration of activated eosinophils and other inflammatory cells into airway tissues, epithelial desquamonon, and by the presence of highly viscous mucus within the airways. The damage caused by this inflammatory response leaves the airways xe2x80x9cprimedxe2x80x9d or sensitized, such that-smaller triggers are required to elicit subsequent asthma symptoms.
A number of drugs are available for the palliative treatment of asthma; however, their efficacies vary markedly. Short-acting xcex22-adrenergic agonists, terbutaline and albuterol, long the mainstay of asthma treatment, act primarily during the early phase as bronchodilators. The newer long-acting xcex22-agonists, salmeterol and formoterol, may reduce the bronchoconstrictive component of the late response. However, because the xcex22-agonists do not possess significant antiinflammatory activity, they have no effect on bronchial hyperreactivity.
Numerous other drugs target specific aspects of the early or late asthmatic responses. For example, antihistamines, like loratadine, inhibit early histamine-mediated inflammatory responses. Some of the newer antihistamines, such as azelastine and ketotifen, may have both antiinflammatory and weak bronchodilatory effects, but they currently do not have any established efficacy in asthma treatment. Phosphodiesterase inhibitors, like theophylline/xanthines, may attenuate late inflammatory responses, but there is no evidence that these compounds decrease bronchial hyperreactivity. Anticholinergics, like ipratopium bromide, which are used in cases of acute asthma to inhibit severe bronchoconstriction, have no effect on early or late phase inflammation, no effect on bronchial hyperreactivity, and therefore, essentially no role in chronic therapy.
The corticosteroid drugs, like budesonide, are the most potent antiinflammatory agents. Inflammatory mediator release inhibitors, like cromolyn and nedocromil, act by stabilizing mast cells and thereby inhibiting the late phase inflammatory response to allergen. Thus, cromolyn and nedocromil, as well as the corticosteroids, all reduce bronchial hyperreactivity by minimizing the sensitizing effect of inflammatory damage to the airways. Unfortunately, these antiinflammatory agents do not produce bronchodilation.
Several new agents have been developed that inhibit specific aspects of asthmatic inflammation. For instance, leukotriene receptor antagonists (ICI-204, 219, accolate), specifically inhibit leukotriene-mediated actions. The leukotrienes have been implicated in the production of both airway inflammation and bronchoconstriction.
Thus, while numerous drugs are currently available for the treatment of asthma, these compounds are primarily palliative and/or have significant side effects. Consequently, new therapeutic approaches which target the underlying cause rather than the cascade of symptoms would be highly desirable. Asthma and allergy share a common dependence on IgE-mediated events. Indeed, it is known that excess IgE production is the underlying cause of allergies in general and allergic asthma in particular (Duplantier and Cheng, Ann. Rep. Med. Chem. 29:73-81 (1994)). Thus, compounds that lower IgE levels may be effective in treating the underlying cause of asthma and allergy.
None of the current therapies eliminate the excess circulating IgE. The hypothesis that lowering plasma IgE may reduce the allergic response, was confirmed by recent clinical results with chimeric anti-IgE antibody, CGP-51901, and recombinant humanized monoclonal antibody, rhuMAB-E25. Indeed, three companies, Tanox Biosystems, Inc., Genentech Inc. and Novartis AG are collaborating in the development of a humanized anti-IgE antibody (BioWorld(copyright) Today, Feb. 26, 1997, p. 2) which will treat allergy and asthma by neutralizing excess IgE. Tanox has already successfully tested the anti-IgE antibody, CGP-51901, which reduced the severity and duration of nasal symptoms of allergic rhinitis in a 155-patient Phase II trial (Scrip #2080, Nov 24, 1995, p.26). Genentech recently disclosed positive results from a 536 patient phase-II/III trials of its recombinant humanized monoclonal antibody, rhuMAB-E25 (BioWorld(copyright) Today, Nov. 10, 1998, p. 1). The antibody, rhuMAB-E25, administered by injection (highest dose 300 mg every 2 to 4 weeks as needed) provided a 50% reduction in the number of days a patient required additional xe2x80x9crescuexe2x80x9d medicines (antihistimines and decongestants), compared to placebo. More recently, Dr. Henry Milgrom et. al. of the National Jewish Medical and Research Center in Denver, Colo., published the clinical results of rhuMAB-25 in moderate to severe asthma patients (317 patients for 12 weeks, iv injection every two weeks) and concluded that this drug is xe2x80x9cgoing to be a breakthroughxe2x80x9d (New England Journal of Medicine, Dec. 23, 1999). A Biologics License Application (BLA) for this product has been submitted to the FDA in June, 2000 jointly by Novartis Pharmaceuticals Corporation, Tanox Inc., and Genetech, Inc. The positive results from anti-IgE antibody trials suggest that therapeutic strategies aimed at IgE down-regulation may be effective.
Cancer and Hyperproliferation Disorders
Cellular proliferation is a normal process that is vital to the normal functioning of most biological processes. Cellular proliferation occurs in all living organisms and involves two main processes: nuclear division (mitosis), and cytoplasmic division (cytokinesis). Because organisms are continually growing and replacing cells, cellular proliferation is essential to the vitality of the healthy cell. The disruption of normal cellular proliferation can result in a variety of disorders. For example, hyperproliferation of cells may cause psoriasis, thrombosis, atherosclerosis, coronary heart disease, myocardial infarction, stroke, smooth muscle neoplasms, uterine fibroid or fibroma, and obliterative diseases of vascular grafts and transplanted organs. Abnormal cell proliferation is most commonly associated with tumor formation and cancer.
Cancer is a major disease and is one of the leading causes of mortality both in the United States and internationally. Indeed, cancer is the second leading cause of death in the United States. According to the National Institute of Health, the overall annual cost for cancer is approximately $107 billion, which includes $37 billion for direct medical costs, $11 billion for indirect costs of lost productivity due to illness and $59 billion for indirect costs of lost productivity due to premature death. Not surprisingly, considerable efforts are underway to develop new treatments and preventative measures to combat this devastating illness.
Currently, cancer is primarily treated using a combination of surgery, radiation and chemotherapy. Chemotherapy involves the use of chemical agents to disrupt the replication and metabolism of cancerous cells. Chemotherapeutic agents which are currently being used to treat cancer can be classified into five main groups: natural products and their derivatives; anthacyclines; alkylating agents; antiproliferatives and hormonal agents.
One embodiment of the present invention discloses benzimidazole compounds that modulate IgE and inhibit cell proliferation. Benzimidazole compounds are known in the prior art, for example in European Patent No. 719,765 and U.S. Pat. No. 5,821,258. Both references, however, disclose compounds that contain an active ingredient that acts on DNA, and are structurally different from the benzimidazole derivatives of the current invention. The compounds of the prior art alkylate DNA and there is no suggestion in the references that the disclosed benzimidazole compounds modulate IgE or inhibit the cell proliferation. Further, the compounds described in both references are described as anticancer, antiviral or antimicrobial agents. The anti-allergy or anti-asthma properties of the benzimidazole compounds of the current invention have not previously been recognized. Further, in describing the anticancer properties of benzimidazole compounds, these references disclose chemotherapeutic agents that are DNA alkylating agents. The inhibition of cell proliferation using compounds of the present invention is not disclosed.
The present invention discloses several compounds that are active in down-regulating the IgE response to allergens and other provocative stimuli. One compound disclosed for use in the treatment of a condition associated with an excess IgE level and/or abnormal cell proliferation has a formula:
wherein R is selected from the group consisting of H, C1-C5 alkyl, benzyl, p-fluorobenzyl and di-alkylamino alkyl, wherein said C1-C5 alkyl is selected from the group consisting of a straight chain, branched or cyclic alkyl;
wherein R1 and R2 are independently selected from the group consisting of H, alkyl, substituted alkyl, C3-C9 cycloalkyl, substituted C3-C9 cycloalkyl, polycyclic aliphatic groups, phenyl, substituted phenyl, naphthyl, substituted naphthyl, heteroaryl and substituted heteroaryl, wherein said heteroaryl and said substituted heteroaryl contain 1-3 heteroatoms, wherein said heteroatom is independently selected from the group consisting of nitrogen, oxygen and sulfur;
wherein said substituted phenyl, substituted naphthyl and substituted heteroaryl contain 1-3 substituents, wherein said substituent is selected from the group consisting of H, halogens, polyhalogens, alkoxy group, substituted alkoxy, alkyl, substituted alkyl, dialkylaminoalkyl, hydroxyalkyl, OH, OCH3, COOH, COORxe2x80x2 CORxe2x80x2, CN, CF3, OCF3, NO2, NRxe2x80x2Rxe2x80x2, NHCORxe2x80x2 and CONRxe2x80x2Rxe2x80x2;
wherein R3 and R4 are independently selected from the group consisting of H, alkyl, aryl, heteroaryl and CORxe2x80x2;
wherein Rxe2x80x2 is selected from the group consisting of H, alkyl, substituted alkyl, C3-C9 cycloalkyl, substituted C3-C9 cycloalkyl, polycyclic aliphatics, phenyl, substituted phenyl, naphthyl, substituted naphthyl, heteroaryl and substituted heteroaryl, wherein said heteroaryl and said substituted heteroaryl contain 1-3 heteroatoms, wherein said heteroatom is independently selected from the group consisting of nitrogen, oxygen and sulfur;
wherein X and Y are independently selected from the group consisting of H, halogens, alkoxy, substituted alkoxy, alkyl, substituted alkyl, dialkylaminoalkyl, hydroxyalkyl, OH, OCH3, COOH, CN, CF3, OCF3, NO2, COORxe2x80x3, CHO and CORxe2x80x3; and
wherein Rxe2x80x3 is a C1-C8 alkyl, wherein said C1-C8 alkyl is selected from the group consisting of a straight chain, branched or cyclic alkyl.
A compound of the aforementioned genus may contain a polycyclic aliphatic group which is selected from the group consisting of adamantyl, bicycloheptyl, camphoryl, bicyclo[2,2,2]octanyl and norbornyl.
A compound of the aforementioned genus may contain a heteroaryl and a substituted heteroaryl which is selected from the group consisting of pyridines, thiazoles, isothiazoles, oxazoles, pyrimidines, pyrazines, furans, thiophenes, isoxazoles, pyrroles, pyridazines, 1,2,3-triazines, 1,2,4-triazines, 1,3,5-triazines, pyrazoles, imidazoles, indoles, quinolines, iso-quinolines, benzothiophines, benzofurans, parathiazines, pyrans, chromenes, pyrrolidines, pyrazolidines, imidazolidines, morpholines, thiomorpholines, and the corresponding heterocyclics.
Specific compounds of Genus I are also disclosed in accordance with the current invention. These compounds are identified as Compounds I.1 to I.192 and their representative structures are illustrated below.
Another compound for use in the treatment of a condition associated with an excess IgE level and/or abnormal cell proliferation is disclosed in accordance with the present invention. The compound has a formula:
wherein R is selected from the group consisting of H, C1-C5 alkyl, benzyl, p-fluorobenzyl and di-alkylamino alkyl, wherein said C1-C5 alkyl is selected from the group consisting of a straight chain, branched or cyclic alkyl;
wherein R1 and R2 are independently selected from the group consisting of H, alkyl, substituted alkyl, C3-C9 cycloalkyl, substituted C3-C9 cycloalkyl, polycyclic aliphatic groups, phenyl, substituted phenyl, naphthyl, substituted naphthyl, heteroaryl and substituted heteroaryl, wherein said heteroaryl and said substituted heteroaryl contain 1-3 heteroatoms, wherein said heteroatom is independently selected from the group consisting of nitrogen, oxygen and sulfur;
wherein said substituted phenyl, substituted naphthyl and substituted heteroaryl contain 1-3 substituents, wherein said substituent is selected from the group consisting of H, halogens, polyhalogens, alkoxy group, substituted alkoxy, alkyl, substituted alkyl, dialkylaminoalkyl, hydroxyalkyl, OH, OCH3, COOH, COORxe2x80x2 CORxe2x80x2, CN, CF3, OCF3, NO2, NRxe2x80x2Rxe2x80x2, NHCORxe2x80x2 and CONRxe2x80x2Rxe2x80x2;
wherein R3 and R4 are independently selected from the group consisting of H, alkyl, aryl, heteroaryl and CORxe2x80x2;
wherein Rxe2x80x2 is selected from the group consisting of H, alkyl, substituted alkyl, C3-C9 cycloalkyl, substituted C3-C9 cycloalkyl, polycyclic aliphatics, phenyl, substituted phenyl, naphthyl, substituted naphthyl, heteroaryl and substituted heteroaryl, wherein said heteroaryl and said substituted heteroaryl contain 1-3 heteroatoms, wherein said heteroatom is independently selected from the group consisting of nitrogen, oxygen and sulfur;
wherein X and Y are independently selected from the group consisting of H, halogens, alkoxy, substituted alkoxy, alkyl, substituted alkyl, dialkylaminoalkyl, hydroxyalkyl, OH, OCH3, COOH, CN, CF3, OCF3, NO2, COORxe2x80x3, CHO and CORxe2x80x3; and
wherein Rxe2x80x3 is a C1-C8 alkyl, wherein said C1-C9 alkyl is selected from the group consisting of a straight chain, branched or cyclic alkyl.
A compound of the aforementioned genus may contain a polycyclic aliphatic group which is selected from the group consisting of adamantyl, bicycloheptyl, camphoryl, bicyclo[2,2,2]octanyl and norbornyl.
A compound of the aforementioned genus may contain a heteroaryl and a substituted heteroaryl which is selected from the group consisting of pyridines, thiazoles, isothiazoles, oxazoles, pyrimidines, pyrazines, furans, thiophenes, isoxazoles, pyrroles, pyridazines, 1,2,3-triazines, 1,2,4-triazines, 1,3,5-triazines, pyrazoles, imidazoles, indoles, quinolines, iso-quinolines, benzothiophines, benzofurans, parathiazines, pyrans, chromenes, pyrrolidines, pyrazolidines, imidazolidines, morpholines, thiomorpholines, and the corresponding heterocyclics.
Specific compounds of Genus II are also disclosed in accordance with the current invention. These compounds are identified as Compounds II.1 to II.90 and their representative structures are illustrated below.
Another compound for use in the treatment of a condition associated with an excess IgE level and/or abnormal cell proliferation is disclosed in accordance with the present invention. The compound has a formula:
wherein R is selected from the group consisting of H, C1-C5 alkyl, benzyl, p-fluorobenzyl and di-alkylamino alkyl, wherein said C1-C5 alkyl is selected from the group consisting of a straight chain, branched or cyclic alkyl;
wherein R1 and R2 are independently selected from the group consisting of H, alkyl, substituted alkyl, C3-C9 cycloalkyl, substituted C3-C9 cycloalkyl, polycyclic aliphatic groups, phenyl, substituted phenyl, naphthyl, substituted naphthyl, heteroaryl and substituted heteroaryl, wherein said heteroaryl and said substituted heteroaryl contain 1-3 heteroatoms, wherein said heteroatom is independently selected from the group consisting of nitrogen, oxygen and sulfur;
wherein said substituted phenyl, substituted naphthyl and substituted heteroaryl contain 1-3 substituents, wherein said substituent is selected from the group consisting of H, halogens, polyhalogens, alkoxy group, substituted alkoxy, alkyl, substituted alkyl, dialkylaminoalkyl, hydroxyalkyl, OH, OCH3, COOH, COORxe2x80x2 CORxe2x80x2, CN, CF3, OCF3, NO2, NRxe2x80x2Rxe2x80x2, NHCORxe2x80x2 and CONRxe2x80x2Rxe2x80x2;
wherein R3 and R4 are independently selected from the group consisting of H, alkyl, aryl, heteroaryl and CORxe2x80x2;
wherein Rxe2x80x2 is selected from the group consisting of H, alkyl, substituted alkyl, C3-C9 cycloalkyl, substituted C3-C9 cycloalkyl, polycyclic aliphatics, phenyl, substituted phenyl, naphthyl, substituted naphthyl, heteroaryl and substituted heteroaryl, wherein said heteroaryl and said substituted heteroaryl contain 1-3 heteroatoms, wherein said heteroatom is independently selected from the group consisting of nitrogen, oxygen and sulfur;
wherein X and Y are independently selected from the group consisting of H, halogens, alkoxy, substituted alkoxy, alkyl, substituted alkyl, dialkylaminoalkyl, hydroxyalkyl, OH, OCH3, COOH, CN, CF3, OCF3, NO2, COORxe2x80x3, CHO and CORxe2x80x3; and
wherein Rxe2x80x3 is a C1-C8 alkyl, wherein said C1-C8 alkyl is selected from the group consisting of a straight chain, branched or cyclic alkyl.
A compound of the aforementioned genus may contain a polycyclic aliphatic group which is selected from the group consisting of adamantyl, bicycloheptyl, camphoryl, bicyclo[2,2,2]octanyl and norbornyl.
A compound of the aforementioned genus may contain a heteroaryl and a substituted heteroaryl which is selected from the group consisting of pyridines, thiazoles, isothiazoles, oxazoles, pyrimidines, pyrazines, furans, thiophenes, isoxazoles, pyrroles, pyridazines, 1,2,3-triazines, 1,2,4-triazines, 1,3,5-triazines, pyrazoles, imidazoles, indoles, quinolines, iso-quinolines, benzothiophines, benzofurans, parathiazines, pyrans, chromenes, pyrrolidines, pyrazolidines, imidazolidines, morpholines, thiomorpholines, and the corresponding heterocyclics.
Specific compounds of Genus III are also disclosed in accordance with the current invention. These compounds are identified as Compounds III.1 to III.154 and their representative structures are illustrated below.
For each chemical structure disclosed herein, the hydrogen atoms on the heteroatoms have been omitted for clarity purposes. Where open valences on heteroatoms are indicated, it is assumed that these valences are filled by hydrogen atoms.
A method for treating a disease condition associated with excess IgE and/or abnormal cell proliferation (i.e. cancer) in a mammal is also disclosed. In one aspect, the method comprises the step of administering to the mammal an IgE-suppressing amount or anti-cell proliferation amount of a pharmaceutical formulation comprising at least one benzimidazole compound from the above-disclosed small molecule families.
In accordance with a variation of the method of treatment, the small molecule IgE-suppressing compound may be administered in conjunction with at least one additional agent, which is active in reducing a symptom associated with an allergic reaction. In one embodiment, the small molecule inhibitor may be mixed with at least one additional active ingredient to form a pharmaceutical composition. Alternatively, the small molecule inhibitor may be co-administered at the same time or according to different treatment regimens with the at least one additional active agent.
The at least one additional active ingredient may be a short-acting xcex22-adrenergic agonist selected from the group consisting of terbutaline and albuterol; a long-acting xcex22-adrenergic agonist selected from the group consisting of salmeterol and formoterol; an antihistamine selected from the group consisting of loratadine, azelastine and ketotifen; a phosphodiesterase inhibitor, an anticholinergic agent, a corticosteroid, an inflammatory mediator release inhibitor or a leukotriene receptor antagonist.
In another embodiment, the benzimidazole compound may be administered in conjunction with at least one additional active agent. These active agents include antifungals, antivirals, antibiotics, anti-inflammatories, and anticancer agents. Anticancer agents include, but are not limited to, alkylating agents (lomustine, carmustine, streptozocin, mechlorethamine, melphalan, uracil nitrogen mustard, chlorambucil cyclophosphamide, iphosphamide, cisplatin, carboplatin mitomycin thiotepa dacarbazine procarbazine, hexamethyl melamine, triethylene melamine, busulfan, pipobroman, and mitotane); antimetabolites (methotrexate, trimetrexate pentostatin, cytarabine, ara-CMP, fludarabine phosphate, hydroxyurea, fluorouracil, floxuridine, chlorodeoxyadenosine, gemcitabine, thioguanine, and 6-mercaptopurine); DNA cutters (bleomycin); topoisomerase I poisons (topotecan irinotecan and camptothecin); topoisomerase II poisons (daunorubicin, doxorubicin, idarubicin, mitoxantrone, teniposide, and etoposide); DNA binders (dactinomycin, and mithramycin); and spindle poisons (vinblastine, vincristine, navelbine, paclitaxel, and docetaxel).
In another embodiment, the benzimidazole compounds of the current invention are administered in conjunction with one or more other therapies. These therapies include, but are not limited to radiation, immunotherapy, gene therapy and surgery. These combination therapies may be administered simultaneously or sequentially. For example, radiation may be administered along with the administration of benzimidazole compounds, or may be administered at any time before or after administration of benzimidazole compounds.
A dose of about 0.01 mg to about 100 mg per kg body weight per day of the small molecule IgE inhibitory compound is preferably administered in divided doses daily.
A method for treating a disease condition associated with excess IgE or abnormal cell proliferation in a mammal is also disclosed which comprises the step of administering to the mammal an therapeutic amount of a pharmaceutical formulation comprising at least one compound selected from Genus I, Genus II and/or Genus III.
The methods provided herein for treating diseases and processes mediated by undesired, uncontrolled or abnormal cell proliferation, such as cancer, involve administering to a mammal a composition of the benzimidazole compounds disclosed herein to inhibit cell proliferation. The method is particularly useful for preventing or treating tumor formation and progresson. In one embodiment of the invention, the compounds and methods disclosed are especially useful in treating estrogen receptor positive and estrogen receptor negative type breast cancers.
Other variations within the scope of the present invention may be more fully understood with reference to the following detailed description.

Benzimidazole compounds for modulating IgE and inhibiting cellular proliferation


A footwear item includes an insole, an outsole, and a midsole. The insole includes an insole top surface, an insole bottom surface, and an insole sidewall. The outsole includes an outsole top surface and an outsole bottom surface. The midsole is positioned between the insole and the outsole. The midsole is configured to nest onto the top surface of the outsole. In at least the heel region, the midsole includes a strobel upper surface and a strobel sidewall configured to nestingly receive a heel region of the insole. In addition, an interface between the strobel upper surface and the strobel sidewall includes a fillet region configured to support and reduce lateral-medial movement of the insole relative to the midsole.

Conventional footwear items such as, but not limited to, casual shoes are made with an upper, a strobel, a midsole, an outsole, and an insole. Typically, the interconnected upper and strobel unit is attached directly to the midsole. In at least one conventional process for making shoes, the midsole, the outsole, or both are constructed around a "last," which is a foot model that primarily defines the shape and function of the shoe as it is constructed. The last can be curved, semi-curved or straight. The shape of the last is used to shape the footwear and allow proper attachment to the sole.
The insole, which can often be removed, is typically formed and inserted into the shoe as an afterthought. The primary purpose of the stock insole that is typically provided with the shoe is to provide some cushioning and lining over the strobel. Most stock insoles are essentially sock liners. They do not provide heel cupping support or arch support for performance and comfort while standing, walking, or running.
The aftermarket insole and orthotic industry has arisen in view of the shortcomings of stock insoles and sock liners. Many companies offer insoles and orthotics, both custom and off-the-shelf, that attempt to provide more comfort and performance. However, the aftermarket insoles are typically not made by the same company as the footwear manufacturer. The insoles are made to fit a wide selection of shoes and boots. To do so, they must compromise the shape so as to fit in a wide selection of footwear. In view of this, insoles typically do not fit tightly within the shoe and can often be moved in both a lateral-medial direction and a fore-aft (e.g., anterior-posterior) direction relative to the midsole. Due to these compromises, aftermarket insoles do not fit exactly to the midsole, resulting in reduced performance and comfort. Furthermore, the insole, if it is to support the heel and arch without collapsing, has to be constructed with strong materials or increased thicknesses. This can add weight, expense, and can unduly reduce the volume of the footwear.
While some variables such as, but not limited to, foot size, foot width, footwear brand, and general utility (e.g., boots, shoes, sandals, etc.) may guide a consumer, it is readily appreciated that obtaining a "perfect" or even close fitting footwear item can be elusive. Fitting properly in the shoe can also be a problem and can affect the support of the insole or orthotic. Consequently, custom fit orthotics have become more popular as a way to improve the fit and comfort of a footwear item. Even though custom fit orthotics can be molded to closely conform to the person's foot, it may still be a challenge to have the custom fit orthotic adequately fit within a particular footwear item. By way of example, a custom fit orthotic may perform and fit well within a dress shoe, but actually be ill-fitting and even uncomfortable when transferred to a work boot, or vice-versa.

This patent is subject to a terminal disclaimer.


The improved gate drive circuit provides a continuous gate current whenever there is sufficient anode-to-cathode voltage difference across the SCR. This approach described herein eliminates the need to monitor and reapply SCR gate current after each commutation due to load current distortions. Previous SCR gate driver designs used a pulse train of gate currents to provide a means of keeping the SCRs turned on. The pulsed gate control approach has gaps in the SCR's operation and requires significant circuitry that dissipates much more drive energy. Energy for this improved driver circuit is derived from the SCR anode-to-cathode voltage differential. This eliminates the need for individual power supplies to provide isolated gate signals for each SCR. This self-powering feature reduces the intricacy of controlling multiple SCRs in multi-phase or unreferenced power systems. Flexibility provided by this method allows high power SCRs to be directly interfaced to a digital processor-type controller.

1. Technical Field
The invention disclosed broadly relates to power circuits and more particularly relates to SCR power circuits.
2. Background Art
Switching a silicon controlled rectifier (SCR) in high power applications requires precise control of the SCR's current to insure proper timing of the device turn-on. Large systems operating from a power line frequently have reactive and electronic loads that cause distortion of the current and voltage waveforms. Polarity reversals of the load current due to this distortion cause undesirable mid-cycle commutation or turn-off of the SCR.
Isolation and control of an SCR has frequently been accomplished in the prior art with a transformer to couple energy between the SCR gate and its controller. Individual drive transformers required for each SCR gate increases the complexity of this prior art driver circuit approach. Transformer gate drivers add significant size and weight to a design and cannot sustain a continuous DC drive signal. The need to resupply gate signals at a high pulse rate places severe performance limits on prior art transformer designs for SCR drive systems.

Self-powered SCR gate drive circuit with optical isolation

International Business Machines Corporation


A drilling system for drilling subsea wellbores includes a tubing-conveyed drill bit that passes through a subsea wellhead. Surface supplied drilling fluid flows through the tubing, discharges at the drill bit, returns to the wellhead through a wellbore annulus, and flows to the surface via a riser extending from the wellhead. A flow restriction device positioned in the riser restricts the flow of the returning fluid while an active fluid device controllably discharges fluid from a location below to just above the flow restriction device in the riser, thereby controlling bottomhole pressure and equivalent circulating density (“ECD”). Alternatively, the fluid is discharged into a separate return line thereby providing dual gradient drilling while controlling bottomhole pressure and ECD. A controller controls the energy and thus the speed of the pump in response to downhole measurement(s) to maintain the ECD at a predetermined value or within a predetermined range.

1. Field of the Invention
This invention relates generally to oilfield wellbore drilling systems and more particularly to subsea drilling systems that control bottom hole pressure or equivalent circulating density during drilling of the wellbores.
2. Background of the Art
Oilfield wellbores are drilled by rotating a drill bit conveyed into the wellbore by a drill string. The drill string includes a drilling assembly (also referred to as the "bottom hole assembly" or "BHA") that carries the drill bit. The BHA is conveyed into the wellbore by a tubing. Coiled tubing or jointed tubing is utilized to convey the drilling assembly into the wellbore. The drilling assembly sometimes includes a drilling motor or a "mud motor" that rotates the drill bit. The drilling assembly also includes a variety of sensors for taking measurements of a variety of drilling, formation and BHA parameters. A suitable drilling fluid (commonly referred to as the "mud") is supplied or pumped from the surface down the tubing. The drilling fluid drives the mud motor and then it discharges at the bottom of the drill bit. The drilling fluid returns uphole via the annulus between the drill string and the wellbore and carries with it pieces of formation (commonly referred to as the "cuttings") cut or produced by the drill bit in drilling the wellbore.
For drilling wellbores under water (referred to in the industry as "offshore" or "subsea" drilling) tubing is provided at the surface work station (located on a vessel or platform). One or more tubing injectors or rigs are used to move the tubing into and out of the wellbore. In sub-sea riser-type drilling, a riser, which is formed by joining sections of casing or pipe, is deployed between the drilling vessel and the wellhead equipment at the sea bottom and is utilized to guide the tubing to the wellhead. The riser also serves as a conduit for fluid returning from the wellhead to the vessel at sea surface.
During drilling, the drilling operator attempts to carefully control the fluid density at the surface so as to prevent an overburdened condition in the wellbore. In other words, the operator maintains the hydrostatic pressure of the drilling fluid in the wellbore above the formation or pore pressure to avoid well blow-out. The density of the drilling fluid and the fluid flow rate largely determine the effectiveness of the drilling fluid to carry the cuttings to the surface. One important downhole parameter during drilling is the bottomhole pressure, which is effectively the equivalent circulating density ("ECD") of the fluid at the wellbore bottom.
This term, ECD, describes the condition that exists when the drilling mud in the well is circulated. ECD is the friction pressure caused by the fluid circulating through the annulus of the open hole and the casing(s) on its way back to the surface. This causes an increase in the pressure profile along this path that is different from the pressure profile when the well is in a static condition (i.e., not circulating). In addition to the increase in pressure while circulating, there is an additional increase in pressure while drilling due to the introduction of drill solids into the fluid. This pressure increase along the annulus of the well can negatively impact drilling operations by fracturing the formation at the shoe of the last casing. This can reduce the amount of hole that can be drilled before having to set an additional casing. In addition, the rate of circulation that can be achieved is also limited. Due to this circulating pressure increase, the ability to clean the hole is severely restricted. This condition is exacerbated when drilling an offshore well. In offshore wells, the difference between the fracture pressures in the shallow sections of the well and the pore pressures of the deeper sections is considerably smaller compared to on-shore wellbores. This is due to the seawater gradient versus the gradient that would exist if there were soil overburden for the same depth.
In order to be able to drill a well of this type to a total wellbore depth at a subsea location, the bottom hole ECD must be reduced or controlled. One approach to do so is to use a mud filled riser to form a subsea fluid circulation system utilizing the tubing, BHA, the annulus between the tubing and the wellbore and the mud filled riser, and then inject gas (or some other low density liquid) in the primary drilling fluid (typically in the annulus adjacent the BHA) to reduce the density of fluid downstream (i.e., in the remainder of the fluid circulation system). This so-called "dual density" approach is often referred to as drilling with compressible fluids.
Another method for changing the density gradient in a deepwater return fluid path has been proposed. This approach proposes to use a tank, such as an elastic bag, at the sea floor for receiving return fluid from the wellbore annulus and holding it at the hydrostatic pressure of the water at the sea floor. Independent of the flow in the annulus, a separate return line connected to the sea floor storage tank and a subsea lifting pump delivers the return fluid to the surface. Although this technique (which is referred to as "dual gradient" drilling) would use a single fluid, it would also require a discontinuity in the hydraulic gradient line between the sea floor storage tank and the subsea lifting pump. This requires close monitoring and control of the pressure at the subsea storage tank, subsea hydrostatic water pressure, subsea lifting pump operation and the surface pump delivering drilling fluids under pressure into the tubing for flow downhole. The level of complexity of the required subsea instrumentation and controls as well as the difficulty of deployment of the system has delayed the commercial application of the "dual gradient" system.
Another approach is described in U.S. patent application Ser. No. 09/353,275, filed on Jul. 14, 1999 and assigned to the assignee of the present application. The U.S. patent application Ser. No. 09/353,275 is incorporated herein by reference in its entirety. One embodiment of this application describes a riserless system wherein a centrifugal pump in a separate return line controls the fluid flow to the surface and thus the equivalent circulating density.
The present invention provides a wellbore system wherein equivalent circulating density is controlled by controllably bypassing the returning fluid about a restriction in the returning fluid path of a riser utilizing an active differential pressure device, such as a centrifugal pump or turbine, located adjacent to the riser. The fluid is then returned into the riser above the restriction. The present invention also provides a dual gradient subsea drilling system wherein equivalent circulating density is controlled by controllably bypassing the returning fluid about a restriction in a riser by utilizing an active differential pressure device, such as a centrifugal pump or turbine located some distance above the sea bed. The present systems are relatively easy to incorporate in new and existing systems.

Drilling system and method for controlling equivalent circulating density during drilling of wellbores


A blast cell system is provided with simple and scalable designs that prevent short cycling of air flow through any pallets in blast cells. The blast cell includes a plurality of suction channels that provide independent fluid pathways for directing the air drawn from different rows in the blast cell into the fan.

Convective air blast freezing is a process by which freezing of items like foodstuffs is facilitated by flowing very cold air over the items via mechanical force. Such air blast freezing can be typically used for very large volumes of goods that are carried on pallets. Airflow of thousands of cubic feet per minute (CFM) can be used for freezing. Blast freezing is typically used on perishable foods (e.g., fruits and meats) geographically near their point of initial food processing. Such goods may then be stored for a short or long period in frozen warehouse, and then shipped to a point close to their use, such as to a grocery store or a warehouse operated by a particular grocer.
Such food decays largely because it includes water, which when not frozen, is a hospitable environment for bacteria and other pathogens. Blast freezing can prevent this process and thus is employed broadly in the food distribution industry. Blast freezing can be a large and expensive consumer of electricity, natural gas, or other mechanisms needed to operate chillers, fans, and other equipment required to perform such large-scale cooling.


Embodiments of this disclosure relate to a method, a device and a computer program product for data protection. The method comprises determining objects selected by a user in a set of objects, and automatically generating one or more corresponding filtering conditions according to the objects selected by the user. The method further comprises automatically setting a predetermined protection policy for objects meeting the filtering conditions in the set of objects. In the embodiments of this disclosure, corresponding filtering conditions are automatically generated according to some protected objects selected by a user to form a dynamic filter, without manually setting the filtering conditions by the user, thereby improving the user experience of a data protection system.

Data protection refers to the protection of data of an organization or individual to prevent data loss due to a failure. Different data protection policies may be set for different types of data, for example, how many backups can be set, whether remote or cloud backup is set, etc. Data can be recovered by backup in the event of a data failure or disaster, thus avoiding unnecessary losses.
With the development of network technologies, data protection systems extend data from a data center to a cloud environment. A user may configure information of cloud storage in a data protection system and then select a disaster-tolerant virtual machine (VM), thus backing up to the cloud regularly. If a production machine of the user is failed and becomes unavailable, a virtual machine may be selected from the data protection system and deployed directly to the cloud until the production machine is recovered.

Method, device, and computer program product for data protection


In one embodiment, the present invention includes power control logic for squelch detection circuitry to enable selective enabling of one or more squelch detection circuits of an interconnect interface in a low power mode. The logic may include a squelch mode control register to select a first mode or a second mode of power control, a second register coupled to the squelch mode control register to receive software settings to indicate which squelch detect circuit(s) to disable in a low power state of the interconnect, and a detector to dynamically detect a logical lane zero of the interconnect in the second mode. Other embodiments are described and claimed.

Modern computer systems are typically formed of many semiconductor components that can communicate together via various interconnects such as present on a circuit board. One common such interconnect mechanism, e.g., for incorporating peripheral devices such as a graphics card, is a Peripheral Component Interconnect Express (PCIe™) protocol in accordance with links based on the PCI Express™ Specification Base Specification version 2.0 (published Jan. 17, 2007) (hereafter the PCIe™ Specification). Such an interconnect can be formed of multiple layers, including a transaction layer, a link layer, and a physical layer.
To reduce power consumption when communications are not occurring on a given interconnect, various mechanisms can be provided. If no communications are likely to occur for some time, the interconnect can be placed in a low power state in which various interconnect circuitry is disabled.
To determine when impending PCIe™ traffic is about to occur when in an idle/sleep condition, squelching is a PCIe™ physical layer input/output (I/O) function to detect such traffic. Squelch logic attempts to detect voltage in receive pins of the interconnect to sense activity and prepare a link layer transaction state machine for proper operation to exit from the electrical state (EL) or lower power state. The squelch logic in the I/O circuit typically includes analog differential amplifiers, integrators and other miscellaneous digital logic. However, such squelch logic can consume significant power, as typically the squelch logic is provided for each lane of an interconnect. As the number of lanes increases, so too does the total squelch power, which can manifest as a substantial portion of the idle power budget, particularly in the low power market.


Particular embodiments described herein provide for an electronic device that can be configured to receive a verbal command to active a device with an unknown label, derive a probable device and a label for the probable device, activate the probable device, determine that the activated probable device is the same device to be activated by the verbal command, and store the label and a description for the device. In some examples, the label is associated with the description.

The Internet has enabled interconnection of different computer networks all over the world. In particular, the Internet provides a medium for exchanging data between different users connected to different computer networks. While the use of the Internet has transformed business and personal communications, it can also create confusion or frustration among some users. For example, for a user to start using a device, the device typically needs to be paired with a system through some interaction. When a new device is connected to the system, that device has to be identified as an instance of a particular type, ownership may need to be verified, and then control has to be taken by the system. Typically, this is done through a corresponding application or a web interface which some users find confusing and frustrating.
The FIGURES of the drawings are not necessarily drawn to scale, as their dimensions can be varied considerably without departing from the scope of the present disclosure.


An external adjustment device includes at least one permanent magnet configured for rotation about an axis with a first handle extending linearly at a first end of the device and a second handle at a second end of the device, the second handle extending in a direction substantially off axis to the first handle. The external adjustment device further includes a motor mounted inside the first handle and a first button located in the proximity to one of the first handle or the second handle, the first button configured to be operated by the thumb of a hand that grips the one of the find handle or second handle. The first button is configured to actuate the motor causing the at least one permanent magnet to rotate about the axis in a first direction.

Scoliosis is a general term for the sideways (lateral) curving of the spine, usually in the thoracic or thoracolumbar region. Scoliosis is commonly broken up into different treatment groups, Adolescent Idiopathic Scoliosis, Early Onset Scoliosis and Adult Scoliosis.
Adolescent Idiopathic Scoliosis (AIS) typically affects children between ages 10 and 16, and becomes most severe during growth spurts that occur as the body is developing. One to two percent of children between ages 10 and 16 have some amount of Scoliosis. Of every 1000 children, two to five develop curves that are serious enough to require treatment. The degree of scoliosis is typically described by the Cobb angle, which is determined, usually from x-ray images, by taking the most tilted vertebrae above and below the apex of the curved portion and measuring the angle between intersecting lines drawn perpendicular to the top of the top vertebrae and the bottom of the bottom. The term idiopathic refers to the fact that the exact cause of this curvature is unknown. Some have speculated that scoliosis occurs when, during rapid growth phases, the ligamentum flavum of the spine is too tight and hinders symmetric growth of the spine. For example, as the anterior portion of the spine elongates faster than the posterior portion, the thoracic spine begins to straighten, until it curves laterally, often with an accompanying rotation. In more severe cases, this rotation actually create a noticeable deformity, wherein one shoulder is lower than the other. Currently, many school districts perform external visual assessment of spines, for example in all fifth grade students. For those students in whom an "S" shape or "C" shape is identified instead of an "T" shape, a recommendation is given to have the spine examined by a physician, and commonly followed-up with periodic spinal x-rays.
Typically, patients with a Cobb angle of 20® or less are not treated, but are continually followed up, often with subsequent x-rays. Patients with a Cobb angle of 40° or greater are usually recommended for fusion surgery. It should be noted that many patients do not receive this spinal assessment, for numerous reasons. Many school districts do not perform this assessment, and many children do not regularly visit a physician, so often, the curve progresses rapidly and severely. There is a large population of grown adults with untreated scoliosis; in extreme cases with a Cobb angle as high as or greater than 90°. Many of these adults, though, do not have pain associated with this deformity, and live relatively normal lives, though oftentimes with restricted mobility and motion. In AIS, the ratio of females to males for curves under 10° is about one to one, however, at angles above 30°, females outnumber males by as much as eight to one. Fusion surgery can be performed on the AIS patients or on adult scoliosis patients. In a typical posterior fusion surgery, an incision is made down the length of the back and Titanium or stainless steel straightening rods are placed along the curved portion. These rods are typically secured to the vertebral bodies, for example with hooks or bone screws, or more specifically pedicle screws, in a manner that allows the spine to be straightened. Usually, at the section desired for fusion, the intervertebral disks are removed and bone graft material is placed to create the fusion. If this is autologous material, the bone is harvested from a hip via a separate incision.
Alternatively, the fusion surgery may be performed anteriorly. A lateral and anterior incision is made for access. Usually, one of the lungs is deflated in order to allow access to the spine from this anterior approach. In a less-invasive version of the anterior procedure, instead of the single long incision, approximately five incisions, each about three to four cm long are made in several of the intercostal spaces (between the ribs) on side of the patient. In one version of this minimally invasive surgery, tethers and bone screws are placed and are secured to the vertebra on the anterior convex portion of the curve. Currently, clinical trials are being performed which use staples in place of the tether/screw combination. One advantage of this surgery in comparison with the posterior approach is that the scars from the incisions are not as dramatic, though they are still located in a visible area, when a bathing suit, for example, is worn. The staples have had some difficulty in the clinical trials. The staples tend to pull out of the bone when a critical stress level is reached.
In some cases, after surgery, the patient will wear a protective brace for a few months as the fusing process occurs. Once the patient reaches spinal maturity, it is difficult to remove the rods and associated hardware in a subsequent surgery, because the fusion of the vertebra usually incorporates the rods themselves. Standard practice is to leave this implant in for life. With either of these two surgical methods, after fusion, the patient's Spine is how straight, but depending on how many vertebra were fused, there are often limitations in the degree of flexibility, both in bending and twisting. As these fused patients mature, the fused section can impart large stresses on the adjacent non-fused vertebra, and often, other problems including pain can occur in these areas, sometimes necessitating further surgery. This tends to be in the lumbar portion of the spine that is prone to problems in aging patients. Many physicians are now interested in fusionless surgery for scoliosis, which may be able to eliminate some of the drawbacks of fusion.
One group of patients in which the spine is especially dynamic is the subset known as Early Onset Scoliosis (EOS), which typically occurs in children before the age of five, and more often in boys than in girls. This is a more rare condition, occurring in only about one or two out of 10,000 children, but can be severe, sometimes affecting the normal development of organs. Because of the fact that the spines of these children will still grow a large amount after treatment, non-fusion distraction devices known as growing rods and a device known as the VEPTR-Vertical Expandable Prosthetic Titanium Rib ("Titanium Rib") have been developed. These devices are typically adjusted approximately every six months, to match the child's growth, until the child is at least eight years old, sometimes until they are 15 years old. Each adjustment requires a surgical incision to access the adjustable portion of the device. Because the patients may receive the device at an age as early as six months old, this treatment requires a large number of surgeries. Because of the multiple surgeries, these patients have a rather high preponderance of infection.
Returning to the AIS patients, the treatment methodology for those with a Cobb angle between 20° and 40° is quite controversial. Many physicians prescribe a brace (for example, the Boston Brace), that the patient must wear on their body and under their clothes 18 to 23 hours a day until they become skeletally mature, for example to age 16. Because these patients are all passing through their socially demanding adolescent years, it is quite a serious prospect to be forced with the choice of either wearing a somewhat bulky brace that covers most of the upper body, having fusion surgery that may leave large scars and also limit motion, or doing nothing and running the risk of becoming disfigured and possibly disabled. It is commonly known that many patients have at times hidden their braces, for example, in a bush outside of school, in order to escape any related embarrassment. The patient compliance with brace wearing has been so problematic that there have been special braces constructed which sense the body of the patient, and keep track of the amount of time per day that the brace is worn. Patients have even been known to place objects into unworn braces of this type in order to fool the sensor. Coupled with the inconsistent patient compliance with brace usage, is a feeling by many physicians that braces, even if used properly, are not at all effective at curing scoliosis. These physicians may agree that bracing can possibly slow down or even temporarily stop curve (Cobb angle) progression, but they have noted that as soon as the treatment period ends and the brace is no longer worn, often the scoliosis rapidly progresses, to a Cobb angle even more severe than it was at the beginning of treatment. Some say the reason for the supposed ineffectiveness of the brace is that it works only on a portion of the torso, and not on the entire spine. Currently a prospective, randomized 500 patient clinical trial known as BrAIST (Bracing in Adolescent Idiopathic Scoliosis Trial) is enrolling patients, 50% of whom will be treated with the brace and 50% of who will simply be watched. The Cobb angle data will be measured continually up until skeletal maturity, or until a Cobb angle of 50° is reached, at which time the patient will likely undergo surgery. Many physicians feel that the BrAIST trial will show that braces am completely ineffective. If this is the case, the quandary about what to do with AIS patients who have a Cobb angle of between 20° and 40° will only become more pronounced. It should be noted that the "20° to 40°" patient population is as much as ten times larger than the "40° and greater" patient population.
Distraction osteogenesis, also known as distraction callotasis and osteodistraction has been used successfully to lengthen long bones of the body. Typically, the bone, if not already fractured, is purposely fractured by means of a corticotomy, and the two segments of bone are gradually distracted apart, which allows new bone to form in the gap. If the distraction rate is too high, there is a risk of nonunion, if the rate is too low, there is a risk that the two segments will completely fuse to each other before the distinction period is complete. When the desired length of the bone is achieved using this process, the hone is allowed to consolidate. Distraction osteogenesis applications are mainly focused on the growth of the femur or tibia, but may also include the humerus, the jaw bone (micrognathia), or other bones. The reasons for lengthening or growing bones are multifold, the applications including, but not limited to: post osteosarcoma bone cancer, cosmetic lengthening (both legs—femur and/or tibia) in short stature or dwarfism/achondroplasia; lengthening of one limb to match the other (congenital, post-trauma, post-skeletal disorder, prosthetic knee joint), nonunions.
Distraction osteogenesis using external fixators has been done for many years, but the external fixator can be unwieldy for the patient. It can also be painful, and the patient is subject to the risk of pin track infection, joint stiffness, loss of appetite, depression, cartilage damage and other side effects. Having the external fixator in place also delays the beginning of rehabilitation.
In response to the shortcomings of external fixator distraction, intramedullary distraction nails have been surgically implanted which are contained entirely within the bone. Some are automatically lengthened via repeated rotation of the patient's limb. This can sometimes be painful to the patient, and can often proceed in an uncontrolled fashion. This therefore makes it difficult to follow the strict daily or weekly lengthening regime that avoids nonunion (if too fast) or early consolidation (if too slow). Lower limb distraction rates are on the order of one mm per day. Other intramedullary nails have been developed which have an implanted motor and are remotely controlled by an antenna. These devices are therefore designed to be lengthened in a controlled manner, but due to their complexity, may not be manufacturable as an affordable product. Others have proposed intramedullary distractors containing and implanted magnet, which allows the distraction to be driven electromagnetically by an external stator. Because of the complexity and size of the external stator, this technology has not been reduced to a simple and cost-effective device that can be taken home, to allow patients to do daily lengthenings.

External adjustment device for distraction device


A method for an image capturing device includes: acquiring a first image of a target object; extracting coordinate information of a first 2D key point corresponding to the target object; acquiring a second image of the target object; acquiring coordinate information of a second 2D key point in the second image according to the coordinate information of the first 2D key point, the first 2D key point and the second 2D key point being the same key point in the target object; acquiring coordinate information of a 3D key point corresponding to the target object, the 3D key point being a key point obtained after a triangulation operation; and determining camera posture information of the second image according to the coordinate information of the first 2D key point, the coordinate information of the second 2D key point, the coordinate information of the 3D key point, and a 3D-2D projection.

In the field of SLAM, when entering a strange environment, a device (for example, a robot or a virtual reality (VR) device) needs to precisely establish a correspondence between time and space.
At present, in a SLAM system, during the tracking of a camera, calculated three-dimensional (3D) points are usually projected on a new frame of two-dimensional (2D) image, and camera posture information of the camera is estimated. To be specific, a manner of 3D-2D correspondences is used to perform tracking.
FIG. 1 is a schematic diagram of acquiring 3D points based on 3D-2D correspondences in the related art. Referring to FIG. 1, during the estimation of camera posture information of a tth frame of image, a (t−1)th frame of image and a (t−2)th frame of image need to be used to perform triangulation on key points, 3D positions (hollow stars in FIG. 1) of the key points are obtained, and the 3D positions of the key points are then used to estimate the camera posture information of the tth frame of image. In the case of fast movement from the (t−2)th frame of image to the tth frame of image, hollow stars only account for a small part of the tth frame of image. When key points in such a small part are used to estimate the camera posture information of the entire tth frame of image, a relatively large error may occur. In addition, a tracking loss tends to occur because of an excessively small quantity of key points in tracking.
The disclosed methods and systems are directed to solve one or more problems set forth above and other problems.

Method for augmented reality display, method for determining pose information, and apparatuses

TENCENT TECHNOLOGY (SHENZHEN) COMPANY LIMITED


A method, communication device and computer program product communicate between the communication device and a second communication device using an instant messaging application. The first device receives contact information identifying the second communication device and determines a contact type for the second communication device from the contact information. If the contact type is a first contact type, the contact information is stored in a first partition of a memory of the communication device. If the contact type is a second contact type, the contact information is stored in a second partition of the memory. The partitions may employ different encryption schemes or one partition may be is unencrypted. A third party has access and control over the second partition. The device communicates with the second communication device using a security policy associated with the contact type.

Field of the Invention
The present invention relates to an instant messaging system and more particularly to a system and method of assigning security levels to different instant messaging contacts based on contact type across multiple device partitions.
Description of the Related Art
Data security in electronic communications is essential for many organizations, particularly in regulated industries, government services and industries in which the electronic communications may contain sensitive, proprietary or confidential information. While the number of platforms for electronic communications have increased (e.g., email, text messaging, instant messaging, social networking, etc.), by in large, a great deal of the electronic communications over mobile networks remains unprotected or minimally protected, placing the content of those communications at risk for interception.
Even in systems where security measures are implemented, these measures are generally applied "across-the-board" to all contacts, or are not applied at all. However, across-the-board measures consume processing, storage and transmission resources and require a certain amount of time to authenticate. While communications with certain contacts may require the use of these measures, other contacts may not require such measures. Additionally, for a particular contact whose conversations do not usually require security measures, or require a modest degree of security, certain messages may be deemed more sensitive than others.

System and method for assigning security levels for instant messaging contacts across device partitions


An aircraft includes a fuselage extending between a forward end and an aft end; a propulsor mounted to the fuselage at the aft end of the fuselage, the propulsor comprising an outer nacelle, the outer nacelle defining an inlet to the propulsor; and a deployable assembly attached to at least one of the fuselage or the outer nacelle and moveable between a stowed position and an engaged position. The deployable assembly alters an airflow towards the propulsor or into the propulsor through the inlet defined by the outer nacelle when in the engaged position. The propulsor further comprises a tail cone, wherein the outer nacelle defines an exhaust with the tail cone, and wherein the plurality of nacelle panels are movable generally along the axial centerline to a position at least partially aft of the exhaust of the outer nacelle when in the engaged position.

A conventional commercial aircraft generally includes a fuselage, a pair of wings, and a propulsion system that provides thrust. The propulsion system typically includes at least two aircraft engines, such as turbofan jet engines. Each turbofan jet engine is mounted to a respective one of the wings of the aircraft, such as in a suspended position beneath the wing, separated from the wing and fuselage. Such a configuration allows for the turbofan jet engines to interact with separate, freestream airflows that are not impacted by the wings and/or fuselage. This configuration can reduce an amount of turbulence within the air entering an inlet of each respective turbofan jet engine, which has a positive effect on a net propulsive thrust of the aircraft.
However, a drag on the aircraft including the turbofan jet engines, also has an effect on the net propulsive thrust of the aircraft. A total amount of drag on the aircraft, including skin friction and form drag, is generally proportional to a difference between a freestream velocity of air approaching the aircraft and an average velocity of a wake downstream from the aircraft that is produced due to the drag on the aircraft.
Accordingly, a propulsor for an aircraft that energizes the wake and improves propulsion efficiency would be useful.


A modular optical fiber distribution unit and related distribution system is provided. The distribution unit includes a shifted fiber arrangement that allows for modular network assembly. For example, the distribution unit includes a distribution body including a plurality of body optical fibers and a field optical fiber leg including a plurality of field optical fibers including at least one active field optical fiber and at least one inactive field optical fiber. Each active field tether optical fiber is optically coupled to one of the body optical fibers and at least one body optical fiber is not coupled to an active field optical fiber. The positioning of the active and inactive field tether optical fibers in a predetermined manner disclosed herein allows for modular network assembly.

The disclosure relates generally to fiber distribution systems and more particularly to an optical fiber distribution system including one or more modular optical fiber unit including an optical fiber arrangement that facilitates the modular system construction.
In conventional optical fiber distribution systems, a lower fiber count branch may be spliced to fiber(s) of the distribution cable at a point along the length of a distribution cable in order to provide network access to users at points along the length of the distribution cable. In this manner, optical network service from the cable is split out to users at various points along the length of the distribution system.

Modular optical fiber distribution system


Logs emitted in a cloud application platform can be cached. Log events emitted by one or more log emitters in the cloud application platform are received. Cache-allocation data that specifies, for each log emitter, a quota for storing log-event data for the log emitter is maintained. For each log emitter of a plurality of log emitters in the cloud application platform, a respective local cache of log events in computer memory is maintained. A global cache for all of the plurality of log emitters in the system is maintained. Each node in the global cache represents a different respective local cache.

A log file is a file that can be used to record events that occur in an operating system or application, including messages generated, computer services accessed, etc. In a multi-tenant environment, each tenant, e.g., a hosted application, a micro-service, etc., can generate log events for different log files so that each tenant may have one associated log file.
Logging services in a multi-tenant environment can present scalability and availability problems as the number of tenants increases. For example, if one tenant begins to consume excessive amounts of logging resources, either in terms of storage space for the logs or delivery performance for transmitting the logs to a consuming application, the logging services available to other tenants can appear to degrade or disappear.
This problem may be referred to as the "noisy neighbor" problem, in which logging services for one tenant are affected by a possibly completely unrelated tenant on the same platform. The noisy neighbor problem is particularly difficult in cloud application platforms in which users, rather than operators of the platform, drive how many tenants there are as well as the volume and frequency of logs that applications on the platform will emit.

Allocation of computing resources for a computing system hosting multiple applications