A mooring system has a pre-existing subsea foundation at a first seabed location and a catenary mooring line connected to the pre-existing foundation and extending to a moored floating unit. A supplementary subsea foundation is installed at a second seabed location to upgrade the capacity of the mooring system. The mooring line is connected to the supplementary subsea foundation while the connection between the mooring line and the pre-existing subsea foundation is maintained.

This invention relates to retrofitting mooring systems, as used in the subsea oil and gas industry, to upgrade the capacity of their subsea foundations to resist tension in mooring lines.
A poster published in Offshore Magazine, October 2013, entitled Mooring systems for offshore floating installations: trends and technology provides a comprehensive overview of the mooring technologies known in the art. That poster may be viewed online at http://www.offshore-mag.com/content/dam/offshore/print-articles/Volume%2073/10/MOORING-010814REV.pdf
Floating surface units or installations used in oil and gas production are moored to the seabed to remain in substantially the same location for many years of production. An example of such an installation is an FPSO (Floating Production, Storage and Offloading) vessel.
Some taut-leg floating production units are known but these require reinforced anchorages to be installed at the outset, which is generally achieved by injecting concrete or grout. The present invention is concerned with the more common catenary mooring lines that have generally catenary curvature when viewed in profile.
Typically, an FPSO will be held in place by a mooring system comprising catenary-shaped mooring lines arranged in groups to define semi-taut legs. When viewed from above, the mooring lines splay apart from neighbouring mooring lines in each group to define a passive spread pattern.
Usually there is one group of mooring lines at each quadrant of an FPSO, hence a total of four groups, radiating outwardly at 90° intervals when viewed from above. If each of the four groups contains three mooring lines, for example, this is known in the art as a 4×3 pattern. Some surface installations, such as turret-moored vessels, are moored with three groups of mooring lines, radiating outwardly at 120° intervals when viewed from above.
FIGS. 1 and 2 show one of the mooring lines 10 of a conventional mooring system for an FPSO 12 floating at the surface 14, as an example of a moored surface installation. The mooring line 10 hangs with catenary curvature under tension between the FPSO 12 and the seabed 18. Whilst curved, the mooring line 10 lies substantially in a vertical plane.
In this example, the mooring line 10 is anchored by a suction anchor or suction pile 16. Most of the length of the pile 16 is embedded in the soil of the seabed 18 to ensure sufficient resistance to tension in the mooring line 10 when the FPSO 12 moves back.
It will be apparent from FIGS. 1 and 2 that the mooring line 10 is attached to the pile 16 at a level below the mid-point of the length of the pile 16, typically between half and two-thirds of the way down from the top of the pile 16. A similar arrangement is also shown, for example, in WO 02/062653 to a predecessor of the Applicant. This arrangement optimises the balance of forces that act on the pile 16: connecting the mooring line 10 at or nearer to the top would tend to cause rotation of the pile 16, which would require a bigger pile to withstand a given tension in the mooring line 10.
It follows that a short bottom part of the mooring line 10, typically 10 m to 20 m long, is buried in the soil of the seabed 18 beside the pile 16. That buried bottom part is sometimes called a 'forerunner'.
A drag anchor, also embedded in the seabed 18, may be used instead of a pile 16 as a mooring foundation for a surface installation such as an FPSO 12. Again, a short bottom part of the mooring line 10 will similarly be buried in the soil of the seabed 18 if a drag anchor is used.
In more detail, the mooring line 10 comprises, in sequence from bottom to top: a bottom or ground chain 20 attached to the pile 16; a section of spiral strand wire (SSW) 22 attached to the ground chain 20; and a top chain 24 that joins the SSW section 22 to the FPSO 12.
The SSW section 22 will usually be of coated steel but could be of a synthetic plastics material instead: references to 'wire' in this specification are not intended to limit the meaning only to metallic wires.
The SSW section 22 constitutes most of the length of the mooring line 10 because, for a given tensile strength, wire is lighter, more compact to store and less expensive than chain. Chains 20, 24 are used instead of wire at the bottom and top of the mooring line 10 to avoid damage to the wire at those vulnerable locations. As a non-limiting example, the ground chain 20 and the top chain 24 may each be about 200 m long whereas the SSW section 22 may be well over 1200 m long.
Various known connectors 26 join the successive components of the mooring line 10. Different types of connector 26, such as chain connectors and shackles, will typically be used at different locations along the mooring line 10.
It will be apparent from the detail view of FIG. 2 that the ground chain 20 is in two sections, namely a lower section 28 and an upper section 30. Thus, in sequence from the bottom to the top of the mooring line 10: the lower section 28 of the ground chain 20 is attached to a buried side wall of the pile 16; the upper section 30 of the ground chain 20 is connected to the lower section 28 by a first connector 26; the SSW section 22 is connected to the upper section 30 of the ground chain 20 by a second connector 26; and the top chain 24 is connected to the SSW section 22 by a third connector 26.
The lower section 28 of the ground chain 20 is attached to the pile 16 before the pile 16 is overboarded from a surface installation vessel and lowered to penetrate the seabed 18. Thus, the lower section 28 of the ground chain 20 and the first connector 26 are buried under the seabed 18 as part of the bottom 'forerunner' part of the mooring line 10.
The upper section 30 of the ground chain 20 extends from the buried first connector 26 beneath the seabed 18 to the second connector 26 above the seabed 18, where it joins the SSW section 22. Thus, a short transitional portion of the upper section 26 of the ground chain 20 lies on or close to the seabed 18.
A drawback of the partially-buried ground chain 20 arises from inevitable movement of the ground chain 20, in use, relative to the surrounding soil of the seabed 18. For example, all parts of the mooring line 10, including the ground chain 20, will move in response to motion of the FPSO 12 under wind and wave action. Similarly, all parts of the mooring line 10 will be moved by other seawater dynamics acting on the mooring system, such as ocean currents, especially in deeper water.
The resulting movements of the ground chain 20 also move the adjacent soil of the seabed 18. Over time, this may create a trench without soil around and above the previously-buried part of the ground chain 20 beside the pile, hence potentially reducing the capacity of the pile 16. Similarly, a drag anchor could slip and lose its intended position. The result is that, after several years, the actual capacity of the foundation may be significantly lower than was originally intended.
In other cases, the tension applied by a mooring line to a foundation may be greater than was originally intended. For example, the floating surface installation may be enlarged or a mooring line handling system may be upgraded.
For these reasons, it may be necessary to upgrade the capacity of a subsea foundation from time to time. Upgrading capacity may involve recovering original capacity that has been lost by a foundation over time. Alternatively, or additionally, upgrading capacity may involve improving the original capacity of a foundation.
Conventionally, upgrading the capacity of a subsea foundation involves installing a new, more efficient foundation in the seabed near the old foundation. Next, part of the mooring line is disconnected from the old foundation to reconnect it to the new foundation. The old foundation is then redundant.
Disconnecting a mooring line from an existing foundation, or even slackening a mooring line to reduce tension, disadvantageously increases the load on other parts of the mooring system. It is a lengthy and costly operation that introduces a risk of the surface installation losing its position, especially if sea conditions deteriorate during the operation.
WO 2008/129320, to a predecessor of the Applicant, discloses a frame that is used for connecting mooring line elements on the seabed. In a reverse operation, the frame can also be used to separate mooring line elements. The frame comprises pulling means to connect mooring line elements. However, the mooring line elements cannot have residual tension in them. Thus, the frame of WO 2008/129320 cannot be used on a live tensioned line; a line from the floating surface installation must first be slackened.
U.S. Pat. No. 5,061,131 discloses an alternative approach involving extra weights that sharply increase mooring resistance in the event of extreme drift. However, the possible size of such weights is limited on a permanent mooring and in any event would not provide a sufficient upgrade in tension-resisting capacity. Also, the weights apply a permanent shear stress to the mooring lines.
WO 94/16936 relates to a twin-anchor mooring arrangement for a floating vessel, in which a first drag anchor is attached at an end of a mooring line and a second drag anchor is slidable along the mooring line to a second anchoring position.
US 2009/123235 relates to a pile anchor system for an offshore structure. The system includes an original pile attached to a mooring line, and a supplementary pile installed in the vicinity of the original pile. The supplementary pile is attached to the original pile by means of a coupling member, but is not attached to the mooring line itself.
U.S. Pat. No. 7,976,246 describes a system for creating a deep water mooring spread by successively installing independent suction piles from a floating vessel.

Upgrading subsea foundations of mooring systems


A method for operating a wind turbine having at least one blade includes determining an ambient air operating envelope and controlling a power output of the wind turbine at least partially based on the determined ambient air operating envelope. Determining an ambient air operating envelope includes measuring at least one of an ambient air temperature, an ambient air pressure, an ambient air humidity, and wind turbine power output. The method also includes comparing at least one of a measured ambient air temperature, a measured ambient air humidity and a measured ambient air pressure to predetermined ambient air temperature, pressure and humidity values. The method further includes referencing the predetermined ambient air temperature, pressure and humidity values to at least one operational parameter of the wind turbine. The method also includes determining if an existing wind turbine power output is within a range associated with the determined ambient air operating envelope.

This invention relates generally to wind turbines, and more specifically to methods and apparatus for controlling operation of a wind turbine.
Generally, a wind turbine includes a rotor having multiple blades. The rotor is sometimes mounted within a housing, or nacelle, that is positioned on top of a base, for example a truss or tubular tower. At least some known electric utility grade wind turbines (i.e., wind turbines designed to provide electrical power to an electric utility grid) can have rotors of 30 meters (m) (98 feet (ft)) or more in diameter. The rotor blades transform mechanical wind energy into a mechanical rotational torque that drives one or more generators. The generators are sometimes, but not always, rotationally coupled to the rotor through a gearbox. The gearbox steps up the inherently low rotational speed of the turbine rotor for the generator to efficiently convert the rotational mechanical energy to electrical energy, which is fed into the electric utility grid. Gearless direct drive wind turbine generators also exist.
Seasonal changes to the ambient air conditions, for example changes to ambient air temperature and/or pressure, may affect performance of at least some known wind turbines. For example, the normal international engineering code (IEC) design envelope of a wind turbine defines loads acting on the wind energy turbine within a temperature range from about +40 degrees Celsius (° C.) (about 100 degrees Fahrenheit (° F.)) to about −20° C. (about −30° F.). Operation of a wind turbine below this temperature range may require new load calculations which will exceed the design load envelope if no countermeasures are taken, possibly resulting in the need of new, reinforced components. At least some known wind turbines, when subjected to cold weather conditions with ambient air temperature values below the lower temperature limit of the allowable temperature range, are shut off, which is disadvantageous insofar as no electric output power is generated.
Another example of seasonal changes affecting wind turbine performance is that air temperature-corrected turbine performance of at least some known wind turbines may be lower in the summer than in the winter. For example, a probability of the rotor blades of at least some known wind turbines to stall increases during summer conditions when ambient air temperatures are typically higher. Such stalling reduces a potential electric power output of the wind turbine. Moreover, reestablishment of airflow around at least some known wind turbine rotor blades after stalling may cause a short-term increase in generator speed and/or electric power output that may be difficult for a controller of the wind turbine to process. Such controller processing difficulty may increase a probability of the wind turbine to be disconnected from an electric grid due to over-speed and/or over-production conditions.


A method for determining a measurement time period for measuring a propagation environment in a wireless station set having a plurality of wireless stations, between which wireless communication is made using a channel selected from a plurality of channels different in frequency. The method includes the steps of: obtaining a measurement time period in another wireless station set having a plurality of wireless stations; and determining the measurement time period in the own wireless station set so as to have a time period that does not overlap the obtained measurement time period.

The present invention relates to a wireless communication technology using a channel selected from a plurality of channels different in frequency.
A mobile wireless communication system is known in which communication is made within a wireless station set including a base station and terminal stations. The base station transmits beacons for transporting various types of information to the terminal stations. To avoid interference with beacons used in other wireless station sets, synchronization must be secured between base stations to ensure non-overlapping in the timing of beacons.
FIG. 21 is a view demonstrating a method for securing synchronization among base stations. This method is disclosed in Japanese Laid-Open Patent Publication No. 11-18143, for example. Referring to FIG. 21, a base station CS-N is transmitting beacons BBN at predetermined timing. A base station CS-M, once being started, receives a beacon from a neighboring base station. When receiving the beacon BBN from the base station CS-N, the base station CS-M computes the difference m-n between a unique number n of the base station CS-N transmitting the beacon BBN and its own unique number m, and outputs its own beacon BBM at a time shifted from the transmittance time of the base station CS-N by a time corresponding to m-n. Thereafter, when a base station CS-M′ is started, it receives the beacon BBN from the base station CS-N or the beacon BBM from the base station CS-M, and determines the transmittance time of its own beacon in the manner described above with reference to the base station CS-M.
As described above, the base stations in FIG. 21 output their beacons at such timing that no interference or disturbance wave against neighboring base stations will arise, to thereby establish synchronization of the entire system. A related technology is also disclosed in Japanese Laid-Open Patent Publication No. 11-18144.
The above synchronization method is provided for allowing wireless station sets each including a base station and terminal stations to output their beacons without causing interference or issuing disturbance waves against each other, to thereby secure communication routes in the respective wireless station sets.
There is also known a mobile wireless communication system in which communication is made by selecting a channel of a frequency more suitable for communication according to the propagation environment varying with time. In such a system, the propagation environment must be measured in search for a frequency more suitable for communication. During the time period of the measurement of the propagation environment, wireless stations stop issuing their own radio waves.
If a plurality of wireless stations perform the measurement at the same timing, all of them will measure the propagation environment during the time period in which no transmission wave exists, although the propagation environment would have been congested with communications made by the wireless stations during any time period other than the measurement time period. In this case, the measurement result will fail to correctly reflect the degree of congestion at the frequency measured.
If measurement is performed at a fixed period, the following event may occur. That is, once the measurement timing coincides between wireless stations, this state of coincidence of the measurement time period will continue unless any of the wireless stations is stopped in operation and then restarted.

Method for determining a measurement time period


Methods and apparatus for continuously casting thin strip where one or more expansion rings are positioned within at least one of a pair of casting rolls, and automatically measuring a thickness of the cast strip close to the first side edge of the strip using at least one sensor, and if the thickness measured is too thin, automatically decreasing the radial dimension of the expansion ring arranged in close proximity to the first side edge to cause the cylindrical tube to contract and increase the thickness of the cast strip during casting, and if the thickness measured indicates that the thickness of the cast strip is too thick, automatically increasing the radial dimension of the expansion ring arranged in close proximity to the first side edge to cause the cylindrical tube to expand and reduce the thickness of the cast strip during casting.

This invention relates to the casting of metal strip by continuous casting in a twin roll caster.
In a twin roll caster, molten metal is introduced between a pair of counter-rotated horizontal casting rolls that are cooled so that metal shells solidify on the moving casting roll surfaces and are brought together at a nip between them to produce a solidified strip product delivered downwardly from the nip between the casting rolls. The term "nip" is used herein to refer to the general region at which the casting rolls are closest together. The molten metal may be poured from a ladle into a smaller vessel or series of smaller vessels from which it flows through a metal delivery nozzle and nozzles located above the nip forming a casting pool of molten metal supported on the casting surfaces of the casting rolls immediately above the nip and extending along the length of the nip. This casting pool is usually confined between side plates or dams held in sliding engagement with end surfaces of the casting rolls so as to restrict the two ends of the casting pool against outflow.
The twin roll caster is capable of continuously producing cast strip from molten steel through a sequence of ladles positioned on a turret. The molten metal is poured from each ladle in turn into a tundish and then into a moveable tundish before flowing through the metal delivery nozzle into the casting pool. The tundish enables the exchange of an empty ladle for a full ladle on the turret without disrupting the production of the cast strip.
In casting thin metal strips, it is often important to control the edge thickness of the thin metal strip during the casting process. For example, it is not uncommon in certain instances for the portion of the thickness of the strip in close proximity to a side edge of the thin strip to be too thin or wavy. It is additionally important to control the thickness profile to ensure that the strip is not too thick or thin. Therefore, there is a need to better control the thickness of the thin strip at and/or in close proximity to the strip side edges and even more generally across the strip width. There is also a need to provide automated control, as manual control may result in delayed responses to undesired changes in strip thickness, which in turn impacts product quality.

Method for casting metal strip with edge control


A nanocomposite material that is both transparent and electrically conductive is provided. The nanocomposite comprises a nanoporous matrix, preferably formed from nanoparticles, that is internally coated with a transparent conductive material to define an internal conductive path within the nanocomposite. The nanocomposite is substantially transparent over a defined spectral range that preferably includes at least a portion of the visible spectrum, and preferably comprises pores with a mean diameter of less than approximately 25 nm. A bilayer may be formed by depositing a layer of a transparent conductive material on top of a nanocomposite layer, or by depositing a second layer of a nanocomposite having different optical properties. The nanocomposites formed using a combination of sequential and/or concurrent deposition techniques are correspondingly discrete and/or continuously varying structures. Multilayer structures, such as photonic crystal reflectors, may be formed by depositing multiple bilayers, and integrated into devices such as tandem solar cells.

Nanoporous, transparent and conducting films are a novel class of materials that exhibit a unique combination of material properties including transparency, conductivity, well-defined three-dimensional porosity and a large specific surface area. Their built-in continuous network of nanoscale voids provides two distinct advantages over conventional solid thin-film transparent conducting oxides (TCOs). Firstly, their continuously interconnected pore volume can be infiltrated with numerous different reactive species to fabricate devices with a large specific surface area. Secondly, some degree of control can be asserted over the effective index of refraction of mesoporous transparent and conducting films by tuning their degree of porosity.
Such materials have been employed as transparent elements within active optical devices. For example, dye-sensitized solar cells (DSSCs) have been fabricated by infiltrating the voids within titania (TiO2) nanoparticle films with a photosensitive dye and an electrolyte. The nanoscale porosity of the TiO2 nanoparticle film provides the large specific surface area required to adsorb sufficient amounts of light-harvesting molecules within the DSSC.
An advantage of nanoporous transparent and conducting films is that their properties can be tuned by controlling their degree of porosity. For example, silica has an index of refraction of about 1.5 at a wavelength of 600 nm, while a nanoparticle film composed of silica nanoparticles with a porosity of 27% exhibits an effective index of refraction of about 1.3.
Numerous methods of fabricating nanoporous transparent and conducting films have been reported in the literature. For example, such films have been fabricated using the Evaporation-Induced Self-Assembly (EISA) process.[1] More specifically, Fattakhova et al. have used poly(ethylene-co-butylene)-b-poly(ethylene oxides), referred to as "KLE's", as block co-polymers in the EISA process to prepare crystalline and transparent indium tin oxide (ITO) layers with well-ordered, accessible nanoporosity and good electrical conductivity.[2]
As another example, porous TCO films can be prepared by glancing angle deposition (GLAD) (U.S. Pat. No. 6,206,065). In the GLAD process, a thin film of plural columns extending from a surface of a substrate are initially formed. These columns are referred to as "seed posts" which are exposed to a vapor flux incident at an oblique angle. During the deposition, these seed posts grow in a columnar fashion while shadowing the surrounding regions from the incoming flux of vapor. Furthermore, the growth direction of the columns can be controlled by altering the oblique angle from which the vapor flux arrives. The resulting films are anisotropic, porous, and highly structured.
Nanostructured transparent conducting electrodes have also been made by infiltrating a nanoporous structure with a conducting material by means of electrodeposition (U.S. Pat. No. 7,594,982). In this three-step process a transparent conducting layer is first deposited onto a substrate. Secondly, a nano-architected porous film with interconnected pores is deposited onto the transparent conducting layer. Although this nano-porous film must be made from a transparent material, it does not necessarily need to be made from a conductive material, thus as an example, a porous silica film formed using the EISA technique would suffice. In the third and final step electrodeposition is used to fill the pores in with a conducting material.
In yet another example, Lin et al. [5] prepared porous electrodes by using metallorganic chemical vapour deposition (MOCVD) to deposit indium tin oxide (ITO) into the void space of a porous glass matrix. However, the transmittance of these porous glass-ITO composite films was low on account of the visible light being scattered by its micropores. In particular, the optical transparency of the composites was just 32% when measured with an integrating sphere in order to include diffusely transmitted light.
Another method of fabricating nanoporous transparent conducting electrodes is to simply spin- or dip-coat preformed nanoparticles dispersed in solution onto flat substrates.[3,4] Although the transparency of these films can be made to be quite high (>90% in the visible), they must be annealed at high temperatures (of about 500° C.) in order to lower their resistivity.
Recently, nanoporous films have been employed as elements of photonic crystal devices. The possibility of utilizing photonic crystals to manipulate light was first introduced independently by both Yablonovitch and John.[5,6] In short, photonic crystals are a unique class of optical materials that interact with electromagnetic waves causing them to diffract and form interference patterns within the photonic crystal, giving rise to many interesting optical phenomena. For example, photonic crystals can be engineered to possess a photonic band-gap (PBG) over a specified spectral range within which light cannot propagate; in this case incident light will undergo 100% reflection.
Bragg-reflectors, also recognized as one-dimensional photonic crystals (1 D photonic crystals),[8] have been subjected to scientific investigation since the 19th century when Lord Rayleigh showed that light within a specified spectral range incident onto their surface undergo complete reflection.[5] Today, the optical properties of Bragg-reflectors are well-understood, where theoretical advances in the field have shown that 1D photonic crystals can be used to construct optical diodes, which reflect light incident from one side while transmitting light incident from the other side,[10] and omnidirectional reflectors, which completely reflect incident photons over a specified spectral range regardless of their incident angle or polarization.[11,12] Furthermore, owing to their simplicity, Bragg-reflectors have been used to construct numerous optical devices such as Fabry-Perot interferometers,[13] optical resonators for distributed feedback lasers,[14] and optical cavities for controlling the spontaneous emission rates and spectra from emitting media,[15] which is particularly useful for light emitting diodes.
Bragg-reflectors are most commonly fabricated by alternately depositing films from two materials having a differing index of refraction onto a flat substrate. For example, one bi-layer within a Bragg-reflector can be fabricated by first depositing a film from "material A" and then subsequently depositing a film from "material B". Using this procedure, any number of bilayers can be successively deposited in order to build up the Bragg-reflector to a desired thickness. Moreover, the thickness of the films within the Bragg-reflector can be easily manipulated in order to set the spectral position of the Bragg-diffraction peak at a desired wavelength. Likewise photonic defect states can be easily incorporated into these Bragg-reflectors by appropriately tuning the thicknesses of selected layers during the fabrication process.
The aforementioned method of fabricating Bragg-reflectors can be modified in order to create two- and three-dimensional photonic crystals. One method of achieving this is to deposit the Bragg reflector onto a two- or three-dimensionally patterned substrate.[23] A second method is to etch either a two- or three dimensional pattern through the Bragg reflector. This may be done using electron beam lithography, ion beam etching or other dry or wet etching techniques. The pattern etched through the Bragg reflector may be an array of holes or lines and may be aligned normal to the substrate surface or at an arbitrary angle through the use of, for example, angle ion beam etching.[24] The periodicity of two- or three-dimensional photonic crystals formed in this manner can be set by tuning the thickness of the layers within the structure. Also, photonic defect states can be purposely introduced into these two- or three-dimensional photonic crystals either by altering the thickness of certain layers within the structure or by altering the pattern etched through the structure at specific points.
Recent advances in the field of 1D photonic crystals have involved fabricating Bragg-reflectors from novel nanomaterials primarily to impart added functionality to the photonic material.[16,17] For example, Bragg-reflectors made from nanoporous titania (TiO2) and silica (SiO2) films prepared via template directed sol-gel methods can be employed as color-tunable sensors because the built-in porosity enables the surrounding environment to infiltrate the 1D photonic crystal thereby altering its optical properties, namely the effective refractive indices, and hence its reflectance characteristics.[18,19]
As a second example, photoconductive Bragg reflectors have been made by alternately spin-coating TiO2 nanoparticle films of two different degrees of porosity and subsequently infiltrating their pores with ruthenium dye.[20] Furthermore, Bragg reflectors made of alternating layers of spin-coated SiO2 and TiO2 nanoparticle films have been fabricated on the rear side of dye-sensitized solar cells (DSSCs) in order to reduce transmission losses by reflecting transmitted light back into the cell.[21,22] In this case the porous structure of the nanoparticle films is occupied by an electrolyte thereby providing the necessary pathway for charge transport through the DSSC.
In another example, a conductive inverse opal photonic crystal has been reported by Bielawny et al. [46], where the inverse opal is formed by infiltrating a poly(methyl methacrylate) opal template with zinc oxide. The conductive inverse opal was integrated into a tandem solar cell as an intermediate reflector for enhancing the efficiency of the solar cell. Unfortunately, such devices, in which 3D photonic crystals are templated and then inverted through numerous process steps, are complex and costly to manufacture.

Transparent conductive porous nanocomposites and methods of fabrication thereof


Methods for enhanced yeast fermentation of plant material through the genetic modification of yeast comprising stably integrating into a yeast an inducible promoter operably linked to a mitochondrial targeting signal as well as at least one restriction enzyme and inducing the expression of the at least one restriction enzyme, wherein the restriction enzyme targets and destroys the mitochondrial DNA of the yeast. DNA constructs comprising at least an inducible promoter operably linked to a mitochondrial targeting signal as well as at least one restriction enzyme for induced expression of at least one restriction enzyme for destruction of mitochondrial DNA as well as transgenic yeast expressing a DNA construct for destruction of mitochondrial DNA and enhanced fermentation, are also disclosed.

All publications cited in this application are herein incorporated by reference.
The budding yeast Saccharomyces cerevisiae is routinely used in fermentations that produce biofuels and other high-value products. This yeast is capable of fermentation of hexoses (e.g., glucose) in the absence or presence of oxygen. Pyruvate is the theoretical endpoint of glycolysis, but continued fermentative metabolism reduces pyruvate to lactate or reduces the pyruvate derivative acetaldehyde to ethanol. The conversion to ethanol is typically favored in S. cerevisiae, although genetic modifications have yielded strains that have a metabolic endpoint of isobutanol or other commercially valuable products. In the presence of oxygen, pyruvate can alternatively be subjected to complete oxidation by enzymes of the tricarboxylic acid (TCA) cycle; the electrons stripped from pyruvate are ultimately donated to oxygen. Consequently, one outcome of glucose metabolism in yeast (and many other organisms) is the coupling of glycolysis (production of pyruvate) to the oxidative degradation of pyruvate with the ultimate transfer of electrons to oxygen (cellular respiration), resulting in the generation of ATP. If glucose is plentiful, S. cerevisiae metabolizes glucose largely (but not exclusively) by fermentation as it provides the most rapid way to gain sufficient energy for biosynthesis and cell growth. As glucose becomes limiting, cellular respiration is engaged to extract energy from alternative carbon sources including the materials that were the produced during the fermentative phase of growth.
Commercial strains of yeast have been engineered and selected to grow vigorously in preparatory phases of the industrial fermentation cycle. Most domestic fuel ethanol plants fermenting a corn feedstock purchase yeast in bulk from a wholesale supplier, often as a "dry active yeast" or "cream yeast". In either case, preparations are produced on a large scale, beginning with small-scale "seed" propagation, and scaling to multi-thousand liter fermenters. In order to enhance biomass, the yeast are cultivated in a highly aerobic environment. Ultimately the yeast are harvested and prepared for sale and shipment to fuel ethanol plants. There, tens of kilograms of the purchased yeast stock are propagated aerobically using the corn mash to enhance the number of yeast cells that are added to the large (40,000 liter and larger) fermenters. This is the production phase of fermentation where anaerobic conditions induce the production of ethanol, isobutanol or other high-value bio-based chemicals.
The foregoing examples of related art and limitations related therewith are intended to be illustrative and not exclusive, and they do not imply any limitations on the inventions described herein. Other limitations of the related art will become apparent to those skilled in the art upon a reading of the specification and a study of the drawings.

Method for enhanced fermentation through the destruction of mitochondrial DNA in yeast


The present disclosure provides embodiments of systems and methods that may be used by an information handling system (IHS) to improve the accuracy of eye tracking data generated by an eye tracking system of the IHS when a user's gaze is not directed to a gaze interaction plane of the eye tracking system. In one embodiment, the method may include receiving first data corresponding to a hinge angle (θ) measured between a first surface and a second surface of the IHS, receiving second data corresponding to a user's gaze on the first surface or the second surface, and using the first data and the second data to provide accurate eye tracking data when the user's gaze is directed to the second surface. When the user's gaze is directed to the first surface, the method may use the second data, but not the first data, to provide accurate eye tracking data.

As the value and use of information continues to increase, individuals and businesses seek additional ways to process and store information. One option available to users is information handling systems. An information handling system (IHS) generally processes, compiles, stores, and/or communicates information or data for business, personal, or other purposes thereby allowing users to take advantage of the value of the information. Because technology and information handling needs and requirements vary between different users or applications, information handling systems may also vary regarding what information is handled, how the information is handled, how much information is processed, stored, or communicated, and how quickly and efficiently the information may be processed, stored, or communicated. The variations in information handling systems allow for information handling systems to be general or configured for a specific user or specific use such as financial transaction processing, airline reservations, enterprise data storage, or global communications. In addition, information handling systems may include a variety of hardware and software components that may be configured to process, store, and communicate information and may include one or more computer systems, data storage systems, and networking systems.
Portable information handling systems, such as laptop computers and 2-in-1 computers, may generally comprise a lid that is rotationally coupled to a base of the IHS. In a traditional clamshell configuration, the lid may be rotationally coupled to the base, so that the lid articulates between a closed position (approximately 0°) to a variety of open positions (e.g., up to approximately 360°) to expose a display screen of the IHS to the user. When the IHS is not in use, the lid may be rotated back to the closed position to enhance portability of the IHS. In general, one or more hinges may be coupled between the lid and the base on a rear surface of the IHS to provide the articulation desired in the clamshell configuration.
In some cases, an information handling system may include one or more display screens for displaying information to the user when the lid is rotated to an open position, and one or more sensors for determining an orientation of the lid with respect to the base (or vice versa). For example, some IHSs may include a sensor on the lid (or on the base) to determine an angle (otherwise referred to as the "hinge angle") between the lid and the base. In such systems, the hinge angle (θ) provided by the sensor may be used to determine whether, e.g., the lid is in a closed/open position, or the system is being used in laptop or tablet mode. In some cases, the hinge angle provided by the sensor may be used by a processing device of the IHS to perform an action for the IHS, such as changing a display orientation of a display screen (e.g., changing between portrait and landscape orientations), changing operating system user states and application modes, and changing backlight segmentation illumination.
Some information handling systems include an eye tracking system to detect the position and/or gaze direction of the user's eyes. In one example, an eye tracking system may include at least one light source positioned to illuminate the user's eyes, at least one photosensor (or camera) positioned to detect light reflected off the user's eyes, and a control unit or other processing device, which is configured to generate eye tracking data based on the light reflected off the user's eyes and detected by the photosensor(s) of the eye tracking system.
As shown in FIG. 1, the generated eye tracking data may include, for example, a gaze point (GP), gaze direction (α), one or more gaze vectors (G1 and/or G2), and/or an inter-pupillary distance (IPD) measurement. The gaze point (GP) is the location of the user's gaze (i.e., the point or region where the user is looking) on a gaze interaction plane (P). The gaze direction (α) is the direction or angle of the user's gaze towards the gaze interaction plane. A gaze vector (G1 or G2) includes the gaze direction (α) and the distance (i.e., the magnitude of the gaze vector) between the gaze point (GP) on the gaze interaction plane (P) and one of the user's eyes located on a pupil plane (E). The inter-pupillary distance (IPD) is the distance between the user's pupils. Some eye tracking systems may be configured to provide all of the eye tracking data mentioned above, while other eye tracking systems may provide only a subset of this data.
To generate eye tracking data, the control unit or other processing device of the eye tracking system may detect "glints" or reflections of light, which are reflected off the user's eyes and detected by the photosensor(s) or camera(s) of the eye tracking system. The detection of "glints" and the calculation of eye tracking data may be achieved using a variety of well-known techniques (including 2D and/or 3D techniques). Once calculated by the eye tracking system, the eye tracking data can be used by a processing device of an IHS to perform an action for the IHS, such as performing operation system window management.
Some information handling systems include a single eye tracking system for tracking the location of the user's gaze on a plurality of display screens. FIG. 2 illustrates an information handling system (IHS) in which a first display screen ("Display 1") is rotationally coupled to a second display screen ("Display 2") via a hinge, which enables the display screens to be positioned at a variety of hinge angles (θ). In the dual-screen system shown in FIG. 2, a single eye tracking system ("s") is mounted onto the first display screen near a bottom peripheral portion of the display screen at an origin point (0, 0, 0). Alternatively, the eye tracking system could be mounted onto the first display screen near a top peripheral portion of the display screen, or could be mounted onto a top or bottom peripheral portion of the second display screen.
When mounted onto the first display screen as shown in FIG. 2, the single eye tracking system may generate relatively accurate eye tracking data when the user's gaze is directed toward the first display screen, since the first display screen is parallel to (or lies within) the gaze interaction plane (P) of the eye tracking system. In some cases, for example, the eye tracking system may provide a relatively accurate gaze point, i (x, y, z), and gaze vector (G) when the user gazes upon the first display screen ("Display 1"). In some cases, a relatively accurate location of the user's eye, e (x, y, z), may also be provided by the eye tracking system as eye tracking data, or may be calculated from the eye tracking data (e.g., gaze point and gaze vector) provided by the eye tracking system.
However, a problem may arise in the dual-screen system shown in FIG. 2 when the user's gaze is directed toward the second display screen ("Display 2"). When the user gazes upon the second display screen, the eye tracking system generates eye tracking data (e.g., gaze point, gaze vector, and/or eye location, etc.) relative to the gaze interaction plane (P) of the eye tracking system. If the second display screen is rotated away from the gaze interaction plane (e.g., if any hinge angle, θ, other than 180° exists between Display 1 and Display 2), the eye tracking data generated by the eye tracking system will not be accurate when the user gazes upon the second display screen. A need, therefore, remains for a system and method that improves the accuracy of the eye tracking data generated by an eye tracking system when the user's gaze is not directed to the gaze interaction plane (P) of the eye tracking system.

Information handling system and method to improve the accuracy of eye tracking data generated by an eye tracking system


The present disclosure provides a compressor system operable for compressing a working fluid such as air. A conditioner is positioned upstream of the compressor to reduce the humidity and in some embodiments may control a temperature of the working fluid entering the compressor. A working fluid aftercooler and a lubricant cooler is positioned downstream of the compressor. A first heat exchange system directs water from a source through the conditioner and then to the aftercooler and oil cooler in parallel. A second heat exchange system directs oil from the compressor to the oil cooler and then to a regenerator prior to reentry into the compressor. A control system with one or more control valves is configured to provide oil to the compressor at a target temperature defined to ensure that the temperature of the discharged compressor is above a pressure dew point temperature.

Industrial compressor systems are configured to produce large volumes of pressurized fluid such as air or the like. Efficiency improvements to compressor systems translate into cost savings for the system operator. Some existing systems have various shortcomings relative to certain applications. Accordingly, there remains a need for further contributions in this area of technology.

Compressor system and lubricant control valve to regulate temperature of a lubricant


In a user interface a plurality of videos are simultaneously played for the purpose of allowing a user to select the desired video on the basis of a plurality of played frames.

Many devices are nowadays equipped with video displaying capabilities, starting with personal computers and laptops, and including digital personal assistants, cellular phones, digital tablets and the like. Movies, and video in general, are selected from menus that show digital information regarding them. However, current UIs only offer static images and title to represent the different movies or other objects. Prior art user interfaces only reveal a single frame from the movie, which is generated by the device (and in some instances can be selected by the user), and this presents a problem because the information that can be retrieved from a single frame is limited and insufficient. For example, commercial movies always start with a studio logo and hence a number of movies can have the same thumb. Another example is if the thumb is chosen from a time in which there is no significant information in the picture. In such cases, it is likely that the user will look for further sources of information before choosing his favorite movie, or will start playing the specific movie and watch part of in order to learn more about it. This process naturally takes time and is inefficient.
It is therefore clear that it would be highly desirable to provide means to display dynamic information for the various videos shown in a selection menu. It is an object of the present invention to provide an improved user interface that simultaneously displays enhanced information, in a dynamic way, regarding a plurality of videos available in a selection menu.
It is a further object of the invention to provide a user interface in which a plurality of videos can be displayed as they are played simultaneously.
It is yet another purpose of invention to provide a method for displaying a plurality of different videos that are simultaneously played in a selection menu and to enable selecting therefrom the one that the user wishes to play in an enlarged or full-screen.
It is still a further object of the invention to provide a method for simultaneously displaying a plurality of segments playing from the same video and to enable selecting therefrom the segment that the user wishes to play in an enlarged or full-screen.
Other objects and advantages of the invention will become apparent as the description proceeds.

Multi-video rendering for enhancing user interface usability and user experience


The invention relates to novel pyridocarbazole derivatives having highly selective action in inhibiting cyclic GMP-phosphodiesterase (hereinafter abbreviated as cGMP-PDE), processes for producing such derivatives, agents containing at least one of such derivatives as an active ingredient for preventing and/or treating pulmonary hypertension, ischemic heart diseases or diseases against which the cGMP-PDE inhibitory action is effective, and intermediates useful for the production of pyridocarbazole derivatives. ##STR1##

The identity of vascular endothelial cell derived relaxing factors has been found to be nitric oxide (hereinafter abbreviated as NO) which, like nitroglycerin used to treat angina pectoris, manifests its vascular relaxing action as mediated by the increase in cyclic GMP (hereinafter abbreviated as cGMP). Briefly, nitrites-like relaxing factors exist endogenously and counteract catecholamine and other endogenous vasoconstricting factors to adjust the tone of blood vessels to thereby contribute to the retention of adequate blood flow. Therefore, the decrease in NO or cGMP is believed to enhance vasotonia and reduce the blood flow in tissue, eventually causing circulatory disorders or ischemic heart diseases.
Increase in vasotonia resulting from damage to coronary endothelial cells which are in the class of NO producing cells is believed to induce insufficiency in the blood flow in myocardial tissue, thereby causing anginal attacks. This results from disorders in the NO-cGMP system working as an endogenous relaxing factor. The vasodilating action of nitrites depends on the diameter of blood vessels for the degree of relaxation and because of their active site specificity (i.e., thicker coronary arteries are relaxed more in tensely), nitrites have so far been in common use. However, the nitrites have a disadvantage in that their action is transient and attenuated during prolonged use. In addition, it has been pointed out that among vasodilators, adenosine enhancers such as dipyridamole which dilate narrow portions of coronary arteries to increase the coronary blood flow increase the myocardial blood flow at normal sites rather than at the lesion, thereby aggravating the ischemia (this phenomenon is generally referred to as "steal") and, hence, showing side effects such as aggravation of angina pectoris and pectoralgia.
While no effective therapeutics have been available for the various pathogenic conditions that manifest pulmonary hypertension, it has recently been reported that NO gas inhalation therapy has certain utility. Since NO gas relaxes blood vessels and lower the pulmonary arterial pressure through the increase in cGMP, it is anticipated that activation of the cGMP producing system dilates selectively pulmonary arteries in the pulmonary circulation, thereby contributing to the treatment of pulmonary hypertension. Calcium blockers and many other vasodilating drugs have so far been used in attempts to treat pulmonary hypertension, none have been commercialized since every one of them is more potent in lowering the systemic blood pressure than the pulmonary arterial pressure. An oxygen therapy has been verified to be effective in achieving improvements after its application. However, oxygen intoxication occurs as a serious side effect and the occurrence of pulmonary lesions such as pulmonary edema and fibrosis has been reported with patients who were on prolonged oxygen therapy at home. The NO gas inhalation therapy is not an exception and the NO gas used in this therapy is one of the air pollutants NO.sub.x and will easily generate NO.sub.2 in the presence of oxygen, thereby potentially causing adverse effects on the airway and lungs; hence, utmost care is required in applying the NO gas and many problems are involved in its prolonged use. On the other hand, suppressing the cGMP degradation system is believed another way to maintain the concentration of cGMP, thereby allowing for selective decrease in the pulmonary arterial pressure. Briefly, an inhibitor of phosphodiesterase (hereinafter abbreviated as PDE) which is an enzyme catalyzing specific hydrolyzation of cyclic GMP holds promise as a new therapeutic free from the aforementioned side effects.
With the inhibition of PDE, cGMP increases, possibly leading to the treatment of ischemic heart diseases or pulmonary hypertension. As of today, PDE has been verified to exist in at least seven isozyme types. Of these, five types of isozymes distribute in many diverse tissues. Two isozymes are capable of selective hydrolyzation of cGMP and they are PDE type I (calmodulin-dependent PDE) and PDE type V (cGMP-PDE). On the other hand, PDE types III and IV hydrolyse cAMP selectively and PDE type II has no substrate selectivity. If the last three isozymes are inhibited, cAMP is increased to cause various obvious side effects including enhanced myocardial contraction and heart rate and depression of systemic blood pressure. Among other things, it is well known that with the inhibition of type III PDE, CAMP increases resulting in enhanced myocardial contraction. It has been reported that increased cGMP in cardiac muscle reduced myocardial contraction but the distribution of PDE type V has not been recognized in cardiac muscle. Therefore, it is anticipated that selective inhibition of PDE type V will produce selective action that is limited in the decrease in systemic blood pressure and side effects on the heart.
It has recently been found that NO releasing compounds show a inhibition of vascular smooth muscle cell proliferation with the intermediary of cGMP. For example, Garg et al. (J. Clin. Invest., 83, 1774-1777, 1989),and Nakaki et al. (Eur. J. Pharmacol., 189, 347-353, 1990) reported that the proliferation of cultured vascular smooth muscle cells isolated from aortic media in rats was suppressed by the treatment of NO releasing compounds nitroprusside, nitroglycerin, isosorbide dinitrate or 8-bromo-cGMP. Therefore, it is suggested that increased cGMP could suppress the proliferation of vascular smooth muscle cells in arteriosclerosis and post-PTCA restenosis.
The cGMP-PDE inhibitors so far disclosed in the art include pyrazolopyrimidone derivatives (see EP-A-526004), purinone derivatives (JP-A 2-88577), phenylpyrimidone derivatives (JP-A 2-295978), quinazoline derivatives (JP-A 6-192235 and JP-A 7-10843 and WO 93/12095) and phthalazine derivatives (WO 96/05176). However, there is no prior art disclosure of the fact that compounds such as the ones claimed in the present invention which have a pyridocarbazole skeleton have the cGMP-PDE inhibitory action. As for the PDE isozyme selectivity, EP-A 526004 and WO 93/12095 teach isozyme selectivity between types V and III but the selectivity has not yet been commercialized in clinical fields to demonstrate a satisfactory action.
Turning back to pyridocarbazole derivatives, their PDE inhibitory action has not yet been reported, nor are there reports that show their vasodilating action and effectiveness for pulmonary hypertension and ischemic heart diseases.
An object, therefore, of the invention is to provide novel compounds that have high isozyme selectivity and potent cGMP-PDE inhibitory action and that cause less side effects to feature high safety.
Other objects of the invention are to provide processes for producing such compounds, intermediates useful for producing them, as well as pharmaceuticals and pharmaceutical compositions containing said compounds. In particular, the invention aims at providing agents for preventing and/or treating pulmonary hypertension, ischemic heart diseases or diseases against which the cGMP-PDE inhibitory action is effective, said agents having solved at least one of the aforementioned problems with the prior art.

Pyridocarbazole derivatives having cgmp-pde inhibitory activity


An actuation circuit for a switch element regulating the power consumption of an inductive energy storage element in a switching converter, used to convert an input voltage into an output voltage, is described. The circuit includes a pulse width modulator circuit configured so as to provide a pulse-width-modulated actuating signal for the switch element depending on a regulating signal dependent on the output voltage and a current measurement signal dependent on a current across the inductive storage element. The circuit further includes an arrangement that provides the current measurement signal, wherein the arrangement for providing the current measurement signal is a measuring and regulating arrangement, configured so as to simulate the current measurement signal from a signal dependent on the output voltage, a signal dependent on the difference between the input voltage and the output voltage, and at least a first sampled value of a signal proportional to the current across the inductive storage element during a period of the pulse-width-modulated actuating signal.

The present invention relates to an actuation circuit for a switch regulating the power consumption in a switching converter. In one case, a switching converter is configured as a buck converter.
Buck converters are switching converters (switched-mode converters) used to convert an input voltage into an output voltage that is lower in comparison to the input voltage. The fundamental layout of such buck converters is described, for example, in Stengl, J. P.; Tihanyi, J.: "Power MOS-FET Practice", 2nd Edition, Pflaum Verlag, Munich, page 176, or in Tarter, R. E.: "Solid-State Power Conversion Handbook", Wiley & Sons, New York, 1993, ISBN 0-471-57243-8, pages 350, 351.
An important element in such a buck converter is an inductive storage element, which is connected to a supply voltage and timed by a pulse width modulated actuating signal.
In order to regulate the output voltage to an approximately constant value, not depending on the current consumption of a load connected to the output terminals, a regulating arrangement is present in such switching converters, which detects the output voltage or the changes in the output voltage. If the output voltage deviates from a given nominal value, the power consumption of the buck converter is changed by changing the on-period, in order to regulate the output voltage back to the nominal value once again. For buck converters that work in so-called current mode control, in order to generate the pulse width modulated actuating signal, one uses the time course of the current across the inductance to generate the actuating signal. This time function, which approximately corresponds to a triangular signal function, is compared to a regulating signal that depends on the output voltage in order to determine the time for the start or end of an on-period. Either the end or the start of the on-period will usually be assigned a fixed time.
A buck converter with current mode operation is described, for example, in Tarter, op.cit., pages 492 to 495.
In such current mode buck converters (CM buck converters), the measuring of the current across the inductance causes problems. In particular, it is difficult to detect a current for which a measurement signal is available both when the switch is closed and when the switch is open, that is, during the entire course of an actuation period of the switch.
To measure the current across the inductance, one can use a measuring resistor connected in series with the inductance, and pick off the voltage across the resistor. However, the voltage across the resistor is related to a potential which varies greatly according to the operating state of the switch, which makes it difficult to evaluate the voltage across the shunting resistor. Furthermore, the power dissipated by this sense resistor is proportional to the square of the load current, therefore the overall efficiency of the converter is severely compromised at high currents.

Actuation circuit for a switch regulating the power consumption in a switching converter


A multilayer optical coating including at least one layer of niobium oxide deposited by DC reactive sputtering.

The present invention relates generally to multilayer optical coatings for transparent substrates, and more particularly to such coatings wherein the layers are deposited by DC reactive sputtering.
DC reactive sputtering is the process most often used for large area commercial coating applications. Metal oxide layers, for example, are deposited by sputtering the appropriate metal in an atmosphere including oxygen. In the reactive sputtering process, the articles to be coated are passed through a series of in-line vacuum chambers each including sputtering sources. The chambers are isolated from one another by vacuum locks. Such system may be referred to as an in-line system or simply a glass coater.
Multilayer antireflection coatings are made by depositing two or more layers of transparent dielectric materials on a substrate. At least one of the layers has a refractive index higher than that of the substrate on which the coating is deposited. The coatings may be designed to reduce reflection at all wavelengths in the visible spectrum. The coatings may yield reflection values less than 0.25 percent over the visible spectrum.
The time it takes to deposit a coating is determined mainly by the number of layers and the sputtering rate of the materials. The use of a glass coater to deposit multilayer antireflection coatings can significantly reduce their cost and thus extend their range of application. Such coatings may be used on picture frame glass and a display case, and as thermal control coatings for architectural and automobile glazings.
Most multilayer antireflection coatings are derived from a basic three layer system. The first or outermost layer of the system has a refractive index lower than that of the substrate and an optical thickness of about one-quarter wavelength at a wavelength of about 520 nanometers (nm). The second or middle layer has a refractive index higher than that of the substrate, and an optical thickness of about one-half wavelength at a wavelength of about 520 nm. The third layer, i.e. the layer deposited on the substrate, has a refractive index greater than that of the substrate but less than the refractive index of the second layer. The optical thickness of the third layer is about one-quarter wavelength at a wavelength of about 520 nm. This basic design was first described in the paper entitled "Three Layered Reflection Reducing Coatings", J. Opt. Soc. Am., Vol. 37, Lockhart and King, pp. 689-694 (1947).
A disadvantage of the basic three layer system is that the refractive indices of the layers must have specific values in order to produce the lowest reflectivity. The selection and control of the refractive index of the third layer is particularly important. Departure from specific values of the refractive index can not be compensated for by varying the thicknesses of the layers.
A simple improvement on the Lockhart and King system is described in U.S. Pat. No. 3,432,225, issued to Rock. The Rock system includes four layers. The first or outermost layer has a refractive index lower than that of the substrate and an optical thickness of about one-quarter wavelength at a wavelength of about 520 nm. The second or middle layer has a refractive index higher than that of the substrate and an optical thickness of about one-half to six-tenths of a wavelength at a wavelength of about 520 nm. The third layer has a thickness of about one-tenth of a wavelength at a wavelength of about 520 nm. The refractive index of the third layer is less than that of the second layer. The fourth layer has an optical thickness of about one-tenth of a wavelength at a wavelength of about 520 nm, and a refractive index greater than that of the third layer and the substrate. The third layer may be the same material as the first layer and the fourth layer may be the same material as the second layer.
The Rock system may be used with different combinations of materials. Differences in refractive indices may be compensated for by different layer thicknesses. Magnesium fluoride (MgFl) can be used to form the outer and third layers. If a higher refractive index material were used for the outer layer, then the refractive index of the second layer would also need to be higher to produce the lowest reflectivity.
Magnesium fluoride may be deposited by sputtering but requires a reactive atmosphere including fluorine or hydrogen fluoride. In a layer system, designed for deposition by DC reactive sputtering in a glass coater, the outer layer is usually silicon dioxide (SiO.sub.2). Silicon dioxide has a refractive index of about 1.46 at a wavelength of about 520 nm. If the reactive index of the first layer is about 1.46, a second layer having a refractive index of about 2.35 would provide the lowest reflection over the visible spectrum. Titanium dioxide (TiO.sub.2) has a refractive index of about 2.35 at a wavelength of about 520 nm. As such, it is commonly used as the high refractive index material in a system deposited by DC reactive sputtering.
The Rock system may require approximately equal thicknesses of titanium dioxide and silicon dioxide. Silicon dioxide may be sputtered four times faster than titanium dioxide. In order to operate at optimum speed, a glass coater may require four times as many sputtering cathodes for titanium dioxide as for silicon dioxide. However, the coater may not have enough chambers to accommodate all of these titanium dioxide cathodes. Thus, the deposition rate for the silicon dioxide will have to be reduced to "keep pace" with the deposition rate of the titanium dioxide. This reduces output and increases production costs.
Materials such as tin oxide (SnO.sub.2) and zinc oxide (ZnO) may be deposited by DC reactive sputtering at a rate at least six times faster than that of titanium oxide. These materials, however, have a refractive index of about 1.9 at a wavelength of 520 nm. The photopic reflection of a four layer antireflection coating using zinc oxide or tin oxide as the second layer would only be about 0.4 percent. The low DC reactive sputter rate for titanium dioxide also presents difficulties in the deposition of highly-reflecting coatings. Highly-reflecting coatings include enhanced metal reflectors which have a metal layer overcoated with low and high refractive index materials. Enhanced reflectors may have four such overcoating layers, including two high and two low refractive index layers arranged alternately. The overcoating layers each have an optical thickness of about one-quarter wavelength at a wavelength of about 520 nm. A low refractive index layer is in contact with the metal layer. The refractive index of the high refractive index material should be as high as possible and the refractive index of the low refractive index material should be as low as possible. This provides optimum reflection enhancement. The high and low index materials should also not absorb visible light.
In the architectural glass coating industry, zinc oxide is used as a layer material for the formation of low emissivity (E) coatings. These coatings are designed to reflect long wavelength infrared radiation while transmitting visible light. They also have a low reflection for visible light from at least one surface. A low E coating may comprise three layers, for example, a silver layer bounded by two dielectric layers. The silver layer must be thick enough to provide high infrared reflection. The dielectric layers reduce reflection from the silver layer in the visible spectrum and thus enhance light transmission through the coated glass. The silver layer is preferably between about 10 and 15 nm thick. The refractive index of the dielectric layers should be relatively high. A material with a refractive index of about 2.35 at a wavelength of about 520 nm, such as titanium dioxide, would be preferred over zinc oxide for the reflection-reducing layers.
Zinc oxide has a refractive index of about 1.9 at a wavelength of about 520 nm. The higher index permits the use of a thicker silver layer while maintaining low visible light transmission and high reflection. For example, using zinc oxide dielectric layers, a silver layer about 8 nm thick produces the lowest reflectivity. For titanium oxide dielectric layers, a silver layer about 130 nm thick produces the lowest reflectivity. The thicker silver layer may also provide higher reflection at longer wavelengths, i.e. a lower emissivity. The thicker silver layer may also provide a higher reflection and lower transmission in the near infrared spectrum, reducing the solar heat load. The industry preference for zinc oxide is substantially based on its high sputtering rate. The lower production costs afforded by the high sputtering rate may be sufficient to justify the less than optimum optical performance. The durability of a layer system incorporating zinc oxide is also poor due to zinc oxide's softness.
It is widely believed that materials which can be deposited at high rates by DC reactive sputtering have relatively low refractive indices. Deposition rate comparisons may be slightly inconsistent from source to source. The type of machine and cathode used may also influence the results. The following approximate rate comparisons serve to illustrate the generalization. The refractive index values cited are the approximate values at a wavelength of about 520 nm. Titanium dioxide has a refractive index of about 2.35, and tantalum oxide (Ta.sub.2 O.sub.5) has a refractive index of about 2.25. Tantalum oxide may be deposited at about twice the rate of titanium dioxide. Zirconium oxide (ZrO.sub.2) has a refractive index of about 2.15 and may be deposited at about twice the rate of titanium dioxide. Tin oxide has a refractive index of about 1.95 and may be deposited at about ten times the rate of titanium dioxide. Zinc oxide has a refractive index of about 1.90 and may be deposited at about ten times the rate of titanium dioxide.
The above-described relationship between the refractive index and the sputtering rate implies that high deposition rates are achievable only with materials having relatively low refractive indices. A more probable explanation, however, is that zinc oxide and tin oxide are semiconductors. As such, oxide build-up on a sputtering target of zinc or tin may not create an insulating layer which lowers the sputtering rate. High oxygen-flow rates are thus possible in the sputtering gas without loss of power. As such, higher oxide deposition rates are possible.
Accordingly, it is the object of the present invention to provide a high refractive index material having a refractive index which is approximately equal to that of titanium dioxide but which may be deposited by DC reactive sputtering at a rate at least four times faster than titanium dioxide and preferably at a rate comparable to zinc oxide.
It is a further object of the present invention to provide a high refractive index material having a high DC reactive sputtering rate which is durable and abrasion resistant.
It is another object of the present invention to provide a simple antireflection layer system which may be deposited at low cost in a large area, in-line sputtering machine.
It is yet another object of the present invention to provide a simple enhanced reflector coating which may be deposited at low cost in a large area in-line sputtering machine.

DC reactively sputtered optical coatings including niobium oxide


A method for determining the position and/or orientation of a catheter or other interventional access device or surgical probe using phase patterns in a magnetic resonance (MR) signal. In the method of the invention, global two-dimensional correlations are used to identify the phase pattern around individual microcoils, which is unique for each microcoil's position and orientation. In one embodiment the position and orientation of a catheter tip can be reliably tracked using low resolution MR scans clinically useful for real-time interventional MRI applications. In a further embodiment, the invention provides real-time computer control to track the position of endovascular devices and interventional treatment systems, including surgical tools and tissue manipulators, devices for in vivo delivery of drugs, angioplasty devices, biopsy and sampling devices, devices for delivery of RF, thermal, microwave or laser energy or ionizing radiation, and internal illumination and imaging devices, such as catheters, endoscopes, laparoscopes, and related instruments.

Catheters and other endovascular access tools have long been used in the art as medical devices to advance therapeutic agents to an anatomic point of interest for examination, diagnosis, and intervention. Accurate positioning of such interventional devices requires monitoring to ensure that the device is being advanced through the correct structures without causing injury, failing mechanically, and for other reasons known to one skilled in the art.
Methods existing in the art for such monitoring include X-ray visualization, as well as MRI tracking of any component of the device designed to be visible on MRI. Many conventional vascular interventional procedures use X-ray imaging technology in which catheters or other probes are inserted into a vein or artery and navigated to specific locations for diagnostic and therapeutic procedures. For example, over 3,000 trans-septal procedures are performed each year in the United States for left sided radio-frequency ablation therapy and mitral valvoplasty procedures. However, 3-6% of these are complicated by aortic or atrial perforations due to incorrect needle positioning. This relatively high complication rate can in part be attributed to the inability to directly visualize critical endocardial landmarks using a two-dimensional projection x-ray fluoroscopy. Conventional X-ray guided interventions suffer from a number of limitations, including: (1) limited anatomical visualization of the body and blood vessels during the examination, (2) limited ability to obtain a cross-sectional view of the target tissue or blood vessel, (3) inability to characterize important pathologic features of atherosclerotic plaques, (4) limited ability to obtain functional information on the state of the related organ, and (5) exposure of the subject to potentially damaging x-ray radiation.
Many invasive cardiovascular procedures, such as traversing total chronic vascular occlusions, would benefit from using MR guidance to accurately deliver interventional medical devices to target locations because MRI methods have fewer limitations than conventional X-ray techniques. For example, U.S. Pat. No. 6,606,513 to Lardo et al describes a method means for an MR trans-septal needle that can be visible on an MRI, can act as an antenna and receive MRI signals from surrounding subject matter to generate high-resolution images, and can enable real-time active needle tracking during MRI guided trans-septal puncture procedures. Interventional cardiology would also benefit from using MR guidance by exploiting MRI's excellent soft tissue contrast. For example, MRI is able to distinguish between infarcted and healthy myocardium to identify an appropriate location for stem cell delivery [1]. MRI is also able to distinguish between plaque and vessel walls [2-3] which facilitates traversing total chronic occlusions. Furthermore, recent research has demonstrated that a complete electrophysiologic study can now be performed entirely under MRI guidance, including the ability to navigate catheters and characterize the temporal and spatial formation of ventricular radiofrequency ablation lesions in vivo.
Additionally, MRI has been shown to guide mitral valvoplasty procedures. As these two therapies account for 95% of all trans-septal procedures performed, it is clear that the ability to perform safe trans-septal needle puncture under MRI guidance will be of great importance as the field of interventional cardiovascular MRI continues to evolve.
In order to perform such procedures under MR guidance, it is necessary to visualize a cardiac catheter and track it using MRI. Another key requirement in minimally-invasive or non-invasive procedures is to integrate the positioning of instruments, needles, or probes with image guidance to confirm that the trajectory or location is as safe as possible, and to provide images that enhance the ability of the physician to distinguish between tissue types. Placement may require acquisition of static images for planning purposes, either in a prior MRI examination or during the interventional MRI session, or real-time images in arbitrary scan planes during the positioning process. (Daniel et al. SMRM Abstr. 1997; 1928; Bornert et al. SMRM Abstr. 1997; 1925; Dumoulin et al. Mag Reson Med 1993; 29: 411-415; Ackerman et al. SMRM Abstr 1986; 1131; Coutts et al., Magnetic Resonance in Medicine 1998, 40:908-13).
Despite the several distinct advantages MRI has over x-ray fluoroscopy, MRI guided positioning of catheters and other devices has numerous challenges related to imaging artifacts, electromagnetic interference, and the necessity for cardiac and respiratory gating and rapid imaging and display. The invention described herein describes a procedure and required hardware to perform MR guided procedures with active tracking of the tip of the interventional device. Such a procedure may improve imaging applications in a number of interventional MRI guided therapies.
Device tracking techniques using MRI can generally be separated into passive and active tracking methods. Passive tracking is based on device visualization due to magnetic susceptibility artifacts. Magnetic susceptibility is a quantitative measure of a material's tendency to interact with and distort an applied magnetic field. Magnetic susceptibility artifacts are generated by inhomogeneities in the magnetic field due to a material with a magnetic susceptibility different than that of tissue [3-6]. Initial attempts to position and visualize endovascular devices in MR imaging were based on passive susceptibility artifacts produced by the device when exposed to the MR field.
U.S. Pat. No. 4,827,931, to Longmore and U.S. Pat. Nos. 5,154,179 and 4,989,608 to Ratner disclose the incorporation of paramagnetic material into endovascular devices to make the devices visible based on magnetic susceptibility imaging. U.S. Pat. No. 5,211,166 to Sepponen similarly discloses the use of surface impregnation of various "relaxants", including paramagnetic materials and nitrogen radicals, onto surgical instruments to enable their MR identification. However, these patents do not provide for artifact-free MR visibility in the presence of rapidly alternating magnetic fields, such as would be produced during echo-planar MR imaging pulse sequences used in real-time MR guidance of intracranial drug delivery procedures. Nor do these patents teach a method for monitoring with MR-visible catheters the outcomes of therapeutic interventions, such as, for example, drug delivery into brain tissues or cerebral ventricles.
Ultrafast imaging sequences generally have significantly lower spatial resolution than conventional spin-echo sequences. Image distortion may include general signal loss, regional signal loss, general signal enhancement, regional signal enhancement, and increased background noise. The magnetic susceptibility artifact produced by the device should be small enough not to obscure surrounding anatomy, or mask low-threshold physiological events that have an MR signature, and thereby compromise the physician's ability to perform the intervention. These relationships will be in part dependent upon the combined or comparative properties of the device, the particular drug, and the surrounding environment (e.g., tissue). No additional processing or hardware is required with passive tracking techniques. However, an additional limitation with passive tracking is that quantitative information about the catheter position or orientation is not obtained. This inhibits automatic scan plane prescription and the catheter must be manually kept within the scan plane.
U.S. Pat. No. 5,470,307 to Lindall discloses a low-profile catheter system with an exposed MR-visible coating containing a therapeutic drug agent, which can be selectively released at remote tissue sites by activation of a photosensitive chemical linker. However, in common with other currently used endovascular access devices, such as catheters, microcatheters, and guidewires, the catheter tip is difficult to see on MRI because of inadequate contrast with respect to surrounding tissues and structures. This makes accurate localization difficult and degrades the quality of the diagnostic information obtained from the image. Also, the mere observation of the location of the catheter in the drug delivery system does not reliably or consistently identify the position, movement and/or efficient delivery of drugs provided through the system. Thus, one objective of this invention is to provide for an MR-compatible and visible device that significantly improves the efficacy and safety of drug delivery at various tissue locations using MR guidance.
An improved method for passive MR visualization of implantable medical devices is disclosed in U.S. Pat. No. 5,782,764 to Werne. This invention minimizes MR susceptibility artifacts and controls eddy currents in the electromagnetic scattering environment, so that a bright "halo" artifact is created to outline the device in its approximately true size, shape, and position. In the method of the invention disclosed by Werne, an ultra thin coating of conductive material comprising 1-10% of the theoretical skin depth of the material being imaged is applied, wherein the susceptibility artifact due to the metal is negligible due to the low material mass. At the same time, the eddy currents are limited due to the ultra-thin conductor coating on the device.
A similar method employing a nitinol wire with Teflon coat in combination with extremely thin wires of a stainless steel alloy included between the nitinol wire and Teflon coat, has been reported in the medical literature by Frahm et al., Proc. ISMRM, 3, 1997, p. 1931.
Active catheter tracking requires the reception of the MR signal by the catheter through a receive coil located on a device that is coupled via a cable to the input port of an MR scanner. Henceforth, a receive coil located on a device and coupled via a cable to the scanner will be referred to as a microcoil. Most active tracking techniques project the magnitude sensitivity pattern of small microcoils located on the catheter onto three orthogonal axes. The location of the micro-coils can then be determined by identifying the peaks of the projections [7-9].
There is, however, a weakness with this approach in that the peaks of the projections do not necessarily correspond to the center of the micro-coil. The magnitude sensitivity profile of a coil also changes with different coil orientations. This makes peak finding through curve fitting difficult. The method is also inherently susceptible to noise; high-resolution scans are needed; and it is not possible to obtain orientation information from the magnitude projections of a single coil [10].
Exemplary of methods for active MR visualization of interventional medical devices is U.S. Pat. No. 5,211,165 to Dumoulin et al., which discloses an MR tracking and localizing system for a catheter based on transmit/receive microcoils positioned near the end of the catheter. Applications of such catheter-based devices in endovascular and endoscopic imaging have been described in the medical literature, for example, Hurst et al., Mag. Res. Med., 24, 1992, pp. 343-357, Kantor et al., Circ. Res., 55, 1984, pp. 55-60; Kandarpa et al., Radiology, 181, 1991, pp. 99; Bomert et al., Proc. ISMRM, 3, 1997, p. 1925; Coutts et al., Proc. ISMRM, 3, 1997, p. 1924; Wendt et al., Proc, ISMRM, 3, 1997, p. 1926; Langsaeter et al., Proc. ISMRM, 3, 1997, p. 1929; Zimmerman et al., Proc. ISMRM, 3, 1997, p. 1930; and, Ladd et al., Proc. ISMRM, 3, 1997, p. 1937.
Various imaging coils for interventional MRI are known in the art. U.S. Pat. No. 5,738,632 to Karasawa discloses an endoscope/rigidoscope with MRI coils located in the distal section of the device. U.S. Pat. No. 5,699,801 to Atalar et al describes a loop antenna for interventional MRI and spectroscopy applications. U.S. Pat. No. 5,348,010 to Schnall et al. discloses an inflatable MRI receiver coil employing a balloon.
U.S. Pat. No. 5,271,400 describes a tracking system for the position and orientation of an invasive device within a patient, wherein the device includes a receiver coil and an MR active sample. The receiver picks up magnetic resonance signals generated by the sample. The frequencies are proportional to the location of the coil along the applied field gradients, since the signals are received in the presence of these magnetic field gradients. The system is designed to enable location of the invasive device and enhanced imaging of a region around the invasive device.
U.S. Pat. Nos. 6,587,706 and 6,560,475 to Viswanathan disclose microcoils which can be used in medical devices to enhance RF response signals and to create fields to enhance imaging capability in MRI imaging systems. The microcoil design includes at least one pair of radially opposed microcoils, each microcoil having an outside microcoil diameter of 6 mm or less, individual windings of each microcoil together defining a geometric plane for each microcoil, and the plane of each microcoil being parallel to the plane of another microcoil in the pair of radially opposed microcoils.
U.S. Pat. No. 6,549,800 to Atalar et al discloses methods for in vivo magnetic resonance imaging, wherein MRI probes are adapted for insertion into a plurality of body orifices in order to evaluate the anatomy of proximate anatomic structures, to diagnose abnormalities thereof and to treat the diagnosed abnormalities. MRI probes are described that are suitable for use in the mediastinum, in the pancreaticohepaticobiliary system, in the tracheobronchopulmonary system, in the head and neck, in the genitourinary system, the gastrointestinal system, the vascular system, and in the evaluation, diagnosis and treatment of internal fluid collections.
U.S. Pat. No. 6,061,587 to Kucharczyk et al. discloses an apparatus and method for targeted drug delivery into a living patient using catheter-based microcoils and magnetic resonance (MR) imaging. The apparatus and method uses MRI to track the location of drug delivery and estimating the rate of drug delivery.
A different approach for remote sensing of location is disclosed by U.S. Pat. No. 5,042,486 to Pfeiler et al. and by U.S. Pat. No. 5,391,199 to Ben Haim. These technologies are based on generating weak radio-frequency signals from three different transmitters, receiving the signals through an RF antenna inside the device, and calculating the distances from the transmitters, which define the spatial location of the device. However, the application of this technology to MRI is problematic due to the simultaneous use of RF signals by the MR scanning. Potential difficulties are the heating of the receiving antenna in the device by the high amplitude excitation RF transmissions of the MRI scanner and artifacts in the MR image.
U.S. Pat. Nos. 5,271,400 and 5,211,165 to Dumoulin et al. disclose a tracking system employing magnetic resonance signals to monitor the position (since mentioned below that orientation information is not available) of a device within a human body. The device disclosed by Dumoulin's inventions have an MR-active sample and a receiver coil which is sensitive to MR signals generated by the MR-active sample. These signals are detected in the presence of MR field gradients and thus have frequencies which are substantially proportional to the location of the coil along the direction of the applied gradient. Signals are detected by sequentially applied, mutually orthogonal magnetic gradients to determine the device's position in several dimensions. The position of the device as determined by the tracking system is superimposed upon independently acquired medical diagnostic images. However, this method cannot directly determine the orientation of the device, may be subject to heating of the coil, and requires time to implement that reduces the temporal resolution available for repeated MRI acquisitions.
Although the patented inventions referenced above provide useful technological advances in the field of image-guided interventions, each invention also has significant inherent limitations. Unlike the present invention, which is based on phase information, the prior art references are based on magnitude information. Phase information can track an interventional device more accurately than magnitude sensitivity information because phase information is more spatially varying than magnitude projections. The present invention also provides notable advantages over the prior art by enabling the position and orientation of a catheter tip to be reliably tracked using low resolution MR scans for real-time interventional MRI applications. The prior art methods are also inherently susceptible to noise; high-resolution scans are needed; and it is not possible to obtain orientation information from the magnitude projections of a single coil [10].

Catheter tracking with phase information


Methods and kits for treating or preventing psoriasis or a symptom associated with psoriasis in a subject are described. The methods involve topical applications to the subject a therapeutically effective amount of an α2 adrenergic receptor agonist, such as brimonidine.

Psoriasis is a common, chronic recurring condition characterized by the eruption of circumscribed, discrete and confluent, reddish, silvery-scaled maculopapules, which occur predominantly on the elbows, knees, scalp, and trunk. Skin rapidly grows and accumulates at psoriatic plaques, i.e., red scaly patches. Psoriasis varies in severity from minor localized patches to complete body coverage. The common forms of the disease include, for example, psoriasis vulgaris, guttate psoriasis, flexural psoriasis, erythrodermic psoriasis, generalized pustular psoriasis and localized pustular psoriasis. The cause of psoriasis is not known, but it is believed to be inherent. It may be aggravated by multiple factors, such as stress, withdrawal of systemic corticosteroid, excessive alcohol consumption, and smoking.
Psoriasis is difficult to treat. Currently available treatments for psoriasis are of limited effectiveness in many patients and, generally, can be used only for a limited duration. For example, topical treatment with coal tar, dithranol (anthralin), corticosteroids like desoximetasone (Topicort), fluocinonide, vitamin D analogues (for example, calcipotriol), retinoids, Argan oil, etc., often irritates normal skin, cannot be used for long periods, and may cause an aggressive recurrence of the condition when the treatment stops. Phototherapy, such as daily, short, non-burning exposure to sunlight or with ultraviolet B (UVB) (315-280 nm) helped to clear or improve psoriasis in some, but not all, patients. Photochemotherapy, i.e., the combined therapy of psoralen and ultraviolet A phototherapy (PUVA), has also been used to treat psoriasis. However, PUVA is associated with nausea, headache, fatigue, burning, itching. Long-term PUVA treatment is associated with squamous cell carcinoma. Psoriasis can also be treated by systemic treatment, e.g., by injection or oral administration of medications, such as methotrexate, cyclosporine and retinoids. However, these medications are known to have toxic side effects, thus cannot be used too frequently. Patients undergoing systemic treatment are required to have regular blood and liver function tests, and pregnancy must be avoided for the majority of these treatments. Most people experience a recurrence of psoriasis after systemic treatment is discontinued. Biologics, such as Amevive®, Enbrel®, Humira®, and Remicade® and Raptiva®, are relatively new therapies that focus on specific aspects of the immune function leading to psoriasis. However, the long-term impact of the biologics on immune function is unknown. Raptiva® was withdrawn by its maker from the US market in April, 2009. They are very expensive and only suitable for very few patients with severe psoriasis.
Agonists of the α2 adrenoceptors have been used therapeutically for a number of conditions including hypertension, congestive heart failure, angina pectoris, spasticity, glaucoma, diarrhea, and for the suppression of opiate withdrawal symptoms (J. P. Heible and R. R. Ruffolo Therapeutic Applications of Agents Interacting with α-Adrenoceptors, p. 180-206 in Progress in Basic and Clinical Pharmacology Vol. 8, P. Lomax and E. S. Vesell Ed., Karger, 1991). Adrenoreceptor agonists, such as clonidine, have been primarily used orally, though a patch formulation is known.
Published US Patent Application US20050276830 discloses α2 adrenergic receptor agonists and their use for treating or preventing inflammatory skin disorders.
There remains a need of novel effective and safe methods and compositions for treating or preventing psoriasis and related symptoms. Such methods and compositions are described in the present application.

This patent is subject to a terminal disclaimer.