text:
|Publication number
|Publication type
|Application number
|Publication date
|Nov 16, 1999
|Filing date
|Jan 20, 1998
|Priority date
|Apr 26, 1996
|Fee status
|Also published as
|Publication number
|Joseph Edward Kegelman, John Paul Mizzer, Edward Anthony Nuzzaci, Allan Tit-Shing Chow
|Original Assignee
|Dade Behring Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (15), Referenced by (95), Classifications (21), Legal Events (13)
|External Links: USPTO, USPTO Assignment, Espacenet
This is a divisional application of U.S. Ser. No. 08/638,618, filed Apr. 26, 1996, now abandoned.
The present invention relates to a method and apparatus for processing liquid samples and, more particularly, for processing biological fluids such as urine, blood serum, plasma, cerebrospinal fluid and the like. In particular, the present invention provides a method and means to automatically process a sample through a sequence of process steps that are carried out during heterogeneous immunoassays.
Fully automated diagnostic analyzers are commercially available to perform chemical assays and immunoassays of biological fluids such as urine, blood serum, plasma, cerebrospinal fluid and the like. Generally, reactions between an analyte in a patient sample and reagents used during the assay, result in generating some sort of signal that can be measured by the analyzer. From this signal the concentration of analyte in the patient sample may be calculated.
Heterogeneous immunoassays are popularly used because their versatility allows both large and small sized analytes to be measured. They require three basic steps: (1) binding analyte to a solid phase, (2) separating the unbound sample analyte from the bound solid phase, and (3) measuring the bound analyte. The physical separation step eliminates most interfering substances, thereby providing for a higher sensitivity. Heterogeneous assays include competitive immunoassays and sandwich immunoassays. Diagnostic analyzers generally employ various processing stations, where processing operations such as sample and reagent addition, separate, wash, and mix are performed to accommodate such assays.
In a competitive assay, an antibody to an antigen contained in a first reagent is typically attached to a derivatized magnetic particle, i.e., particles that are responsive to a magnetic field, to make up a solid phase. The second reagent, consisting of antigen attached to a tag and a patient sample are mixed with the solid phase in a test tube. In the absence of patient antigen, some 50% of the antigen-tag is bound to the antibody of the magnetic solid phase. In the presence of patient antigen, some of the antibodies are attached to patient antigen and are unavailable to the tag antigen. As a result increasing amounts of patient antigen leads to decreasing amount of tag antigen. Magnetic separation clusters the magnetic particles of solid phase with the bound tag into a pellet on the side of the tube. The free tag can then be removed by thorough washing and aspiration. Following separation and removal of free tag, another reagent is added so that the amount of bound tag can be measured.
In a typical sandwich immunoassay, multiple steps are used, i.e., an antibody to an antigen is attached to the magnetic particle in high concentration relative to the amount of patient antigen in a sample. Patient antigen is captured by the antibody on the magnetic particles and then the particles (with attached or captured patient antigen) are separated from interfering substances in the sample. A second reagent, containing a second antibody with an attached tag, is added. This second antibody attaches to the patient antigen, captured by the first antibody on the magnetic particle, and results in the formation of a sandwich so that the second antibody tag is held firmly by the antigen to the first antibody on the magnetic particle. At this point, a thorough washing and magnetic separation permit the determination of bound tag which is in proportion to the patient antigen, the excess tag of the second reagent having been removed by the washing action.
In both types of heterogeneous immunoassays, considerable resources and time are required to achieve a sufficiently high degree of washing so as to eliminate interfering constituents and prevent spurious assay results. The degree to which this is achieved in an automated analyzer is an important contributor to the sensitivity of the analyzer.
High throughput is a desirable feature of such analyzers. An important contributor to maintaining a high throughput is the ability to process a plurality of samples through a variety of the different heterogeneous assay process steps that are needed before the signal measurement step may be undertaken. These multiple process steps tend to limit throughput. In the design of new automatic analyzers, in particular those involving complex "sandwich" heterogeneous immunoassays, which often require many separate processing operations, the ability to be capable of detecting a wide variety of analytes yet occupy a minimum of physical space, is an important performance advantage. Generally, repetitive, uninterrupted operation enhances throughput since a number of vessels can be processed simultaneously.
Repetitive operation is particularly difficult to achieve in the case of heterogeneous "sandwich" immunoassays. This is a particularly difficult procedure even when performed manually. It is a particular problem when the automatic wash procedure is incorporated into an automatic analyzer which is capable of performing multiple types of immunoassays. This necessitates the use of multiple wash stations and this is typically accomplished in automatic analyzers by providing such multiple wash stations. For example, the sensitivity requirements of some heterogeneous assays demand that the washing efficiency must be very high. This is normally achieved by repeated washes, each successive wash removes unwanted liquids and reagents so that a progressively lower background level is achieved. At the same time, such a washing regimen places limitations on use of the various processing resources since the analyzer is required to be stationary in a washing activity. Nominally, an assay requires a total of four separate washes interlaced with four separation steps. Accordingly, an important design feature of the analyzer is the ability of non-washing resources to be productively involved with one sample while another is being washed. However, the several mechanisms required to operate individually the several wash stations and the mechanisms required for the wash stations themselves can become quite expensive.
U.S. Pat. No. 4,459,265 assigned to Clinicon describes an automatic analytical apparatus with a stepwise rotatable circular plate. It carries a plurality of reaction tubes on its periphery with several reagent supply stations arranged at different locations around such periphery. The use of multiple stations does provide the machine with the versatility to carry out several different test methodologies, but again does not provide the necessary washing required for heterogeneous immunoassays. The automatic analytical apparatus described in such Clinicon patent, includes a stepwise rotatable circular plate. It carries a plurality of reaction tubes on its periphery with several reagent supply stations arranged at different locations around such periphery. The use of multiple stations does provide the machine with the versatility to carry out several different pre-assay process steps, but again does not provide the necessary washing required for heterogeneous immunoassays.
A conventional chemical analyzer produced by Hitachi, Inc., Tokyo, Japan, Model Number 7050, links together or "gangs" plural wash probes. When this is accomplished, however, the ability of the instrument to perform multiple analytical procedures at the same time is impaired.
U.S. Pat. No. 5,104,808, Laska et al., assigned to the assignee of the present invention, also describes an analyzer which "gangs" wash probes together. The wash probes are ganged together, but also separated into two groups to achieve the goal of providing washed solid support which contains a minimal amount of the original serum/conjugate matrix. According to Laska et al. the wash means includes at least two wash probes coupled or ganged for simultaneous insertion into the reaction vessels at different processing positions. Further, the wash probes are positioned contiguous to the first one of the sample and/or reagent positions in the sequence. The means for adding sample and/or reagents is disabled each cycle for a number of vessels leading and trailing the first and last vessels receiving sample or reagent, the number corresponding to the number of processing positions between the insertable wash probes.
U.S. Pat. No. 5,183,638, Wakatake; discloses an analyzer in which a reaction vessel is conveyed past several devices for adding and agitating magnetic particles as required during a EIA immunoassay.
U.S. Pat. No. 5,192,505, Sakagami, discloses an analyzer in which two different reaction lines are provided, driven by only one driving device, one line adapted to provide for assay operations involved in a calorimetric measurement, the other line adapted to provide for assay operations involved in an immunization agglutination measurement. An advantage of the analyzer is maintenance of a small physical size.
Another feature used in automated analyzers is the scheduling method used to present the sample to the various assay tools. As described in U.S. Pat. No. 5,212,094, an automatic chemical analyzer uses an odd number of reaction vessels disposed in a circular pattern. The reaction vessels are rotated successively half revolutions of the circular pattern plus the distance between reaction tubes. Using such a pattern, it is possible to collectively situate the washing stations proximate one another and thereby facilitate compactness of the analyzer, however such an analyzer is not capable of performing heterogeneous immunoassays.
The analyzer of U.S. Pat. No. 5,352,612 includes a movable sample support for holding samples arranged in a first, plurality of positions for movement in a first direction. An indexing drive for the sample support moves the samples in the sample support in the first direction in a set of increments wherein each increment represents a movement of the samples an amount corresponding to a number of samples. Such a system enables separation of logical space from physical space in the system, allowing more freedom in placement of mechanical equipment while permitting proper sequencing of operations both in space and in time. This system requires a very complex time-indexing motion of a rotatable sample support that is determined differently for each and every loading of the sample support. As best understood, the movement pattern is determined by the number of pairs of reaction cuvettes. The pattern may vary depending on the assay to be performed and the times spent stopped before different processing resources varies according to the operation of the processing resource.
U.S. Pat. No. 5,380,487, assigned to Pasteur Sanofi Diagnostics, describes an analyzer in which assay resources are assigned fixed operating sequence which begin and end within a time cycle of fixed duration. When different samples having different assay protocols are entered into the analyzer, assay resource requirements for the different samples are determined and "time slots" of the required resources are allocated thereto. Provision is made for handling heterogeneous assays, however because an incubator belt physically intersects the wash wheel, a complex relationship is established between the indexing time of an incubator belt, the indexing time of a wash wheel, and the cycle time of operations performed on reaction vessels as they are moved along the wash wheel. In addition, the control means must determine which time-based assay resources are required to process a test and then check the availability of those assay resources on a cycle-by-cycle basis against the allocation of the resources to the processing of other tests underway. Absent any conflicts in the allocation of assay resources, processing of a reaction vessel will sequentially follow a preceding reaction vessel. Consequently, initiation of the sample processing for a test may be delayed until all the necessary assay resources are available for processing. Although such scheduling may reduce the overall number of indexing cycles necessary to complete the processing of all the tests, scheduling conflicts do delay processing initiation and also result in processing resources being idled.
From a study of the different approaches taken in the prior art to the problems encountered with automated processing of complex heterogeneous immunoassays, there is a need for improved automated analyzers and associated processes for handling samples. At the same time, there is a need for maintaining a high throughput without introducing complex programming and, at the same time, minimizing the physical size of an analyzer. In particular, there is a need for a method of providing bound-unbound analyte separation and wash in a minimum of processing time, in a pattern that enhances/maintains throughput of an automated analyzer.
It is an object, therefore, of the present invention to provide an apparatus for providing the operations required in heterogeneous immunoassays at an increased efficiency and with greatly simplified sample handling techniques.
Many of these disadvantages of the prior art are overcome by using the apparatus and/or methods of this invention. This invention provides a method pre-processing samples having a solid support for heterogeneous assays, using a processing carousel and an incubating carousel, for detecting an analyte in said samples, comprising the steps of:
(a) adding tag reagents, including said solid support, to the sample on said incubating carousel, thereby forming a tagged sample analyte-support complex,
(b) transferring the sample and reagents to the processing carousel,
(c) separating the solid support from at least a portion of the sample and reagents,
(d) washing the solid support,
(e) mixing the solid support with a wash buffer, and
(f) transferring the solid support and buffer to the incubation carousel, and
(g) detecting the analyte.
The number and sequence of steps is selected so that each reaction vessel transferred onto the processing carousel may be removed from the processing carousel at the transfer station for additional processing and returned to the processing carousel using the single transfer station without interrupting the repeated synchronous pattern.
Such a novel approach makes it possible to achieve the rigorous requirements for washing samples required in heterogeneous immunoassays. This is true even though several tests or assays have different reaction times before a wash and may include a reagent addition and incubation step interlaced within the required wash cycles.
Associated with this method is an automatic sample processor for performing pre-immunoassay operations on samples using a solid support. The processor in an analyzer for detecting an analyte, in a sample, using solid supports, said processor comprising:
a processing carousel supporting a plurality of reaction vessels each adapted to hold a sample,
an incubating carousel, supporting a plurality of reaction vessels each adapted to hold a sample, positioned concentrically of said processing carousel,
stationary processing stations positioned adjacent one of said carousels, said stations having means for separating said solid support from the contents of a reaction vessel, means for washing the contents of a reaction vessel, and means for mixing the contents of a reaction vessel,
drive means to rotate each carousel independently of the others, said processing carousel being driven in a repetitive manner to position each of its reaction vessels to positions contiguous predetermined processing stations, and
transfer means for transferring reaction vessels between said carousels, thereby improving processing time by permitting the incubation of all reaction vessels on the incubating carousel without interrupting sample processing on the processing carousel.
The processing stations are positioned in a preselected order to permit the processing carousel to position its reaction vessels in a repetitive sequence of separation and the wash steps. More specifically, the reaction vessel repetitive sequence is separation, wash, and mix. These features provide an analyzer that has a high throughput, reduces the cost of the processing stations by locating similar functions together, and permits samples being processed to be removed at virtually anytime for incubation or measurement.
The invention will be more fully understood from the following detailed description thereof taken in connection with the accompanying drawings which form a part of this application and in which:
FIG. 1 is a schematic plan view of an automated chemical analyzer having a pre-assay processor with a movable processing carousel, an incubating carousel, and a plurality of processing stations for pre-assay processing of samples;
FIG. 2 is a schematic plan view of the pre-assay processor of FIG. 1; and
FIG. 3 is a timing diagram for the pre-assay processor.
The method and apparatus of this invention will be described initially with particular reference to FIGS. 1 and 2 of the drawings. FIG. 1 shows schematically the elements of a conventional automatic chemical analyzer 10 comprising a sample cup carousel 12 supporting a plurality of sample cups 14, a cuvette carousel 16, adapted to hold a plurality of cuvettes 18 and to provide plurality of reagent liquid cartridges 20, illustrated as disposed beneath a cut out portion of a lid 22, which covers various thermally controlled areas. Reagent cartridges 20 are preferably a multi-compartmented container such as those sold under the tradename FLEX™ by E.I. du Pont de Nemours and Co., Inc., Wilmington, Del. Cuvettes 18 may be formed, as done on the Dimension� chemical analyzer sold by E.I. du Pont de Nemours and Co., Inc., Wilmington, Del. by pulling two different composition ribbons of clear film from a cuvette film cartridge, not shown, onto the periphery of the cuvette carousel 16. The cuvette carousel 16, preferably in the form of a wheel, has about a hundred separate cavities for holding cuvette 18, the inner wall of each cavity having an opening to allow transmission of light. A small opening remains at the top of each cuvette 18 to allow the addition of reagent liquid and sample liquid. A sample liquid arm 24 and a wash resource 26 are located proximate the sample cup carousel 12 and cuvette carousel 16. Sample liquid arm 24 supports a conventional sample liquid probe 28 and is mounted to a rotatable shaft 27 so that movement of sample liquid arm 24 describes an arc intersecting the sample cup carousel 12, the cuvettes 18, and the wash resource 26. The wash resource may be used to clean the probe 28.
A first liquid probe 25 is rotatably mounted above cuvette carousel 16 and is adapted to draw reagent liquid from an appropriate reagent liquid cartridge 20 and deposit each reagent liquid within a predetermined cuvette 18 for processing by the chemical analyzer 10. Probe 25 further comprises an ultrasonic mechanism used for aspirating, dispensing and mixing reagents similar to that used in the Dimension� chemical analyzer. Since the hydrating, aspirating, dispensing and mixing mechanisms are well known in the art they need not be described further. Photometic analyzing means, not shown, located beneath the cuvette carousel 16 measures light absorbence through the cuvettes 18 at various wavelengths, from which the presence of analyte in the sample liquid may be determined using well-known analytical techniques. Thus far, the chemical analyzer is conventional and may be, for example, the Dimension� clinical analyzer sold by E.I. du Pont de Nemours and Co., Wilmington, Del.
This invention adds to that analyzer a pre-assay sample processing module 30. This facilitates the several additional steps necessary to perform heterogeneous assays without reducing the ability of the chemical analyzer to maintain a high sample throughput. The processing module 30 permits processing either or both of the sample liquid with analyte and/or the reagent liquid, before they are provided to a cuvette 18 for measurement. Sample processing module 30 comprises two pre-assay sample treatment carousels 32 and 34. These are an inner processing carousel 32 and an outer incubation carousel 34, housed in a thermal chamber, (not shown), the two carousels being concentrically mounted with a common axis and preferably lying in a common plane, both preferably being in the form of a circular carousel. Both carousels are independently moveable and have a predetermined number of vessel holding means which may be clips, not shown, to support a plurality of individual pre-assay reaction vessels 36.
Drive means 31 are provided for independently rotating incubation carousel 34 and processing carousel 32 about a common axis, the drive means typically comprising gear teeth disposed on each of the carousels 32 and 34 and interlacing with pinion gears mounted on the shaft of a motor (not shown). The drive means may be of conventional design. The transfer station 38 described above is one of the plurality of processing stations.
The incubation carousel 34 preferrably contains 45 discrete positions, and is situated to allow reaction vessels 36 to be presented for: 1) reagent addition, 2) sample addition/aspiration, and 3) transfer to/from the cuvette and processing carousels 16, 32, and for load/unload. The carousel may be about 10 inches in diameter. The incubation carousel 34 is driven via a drive means 31 and uses a single home sensor. Its position can be verified at any time via an encoder attached to the stepper motor.
The incubation carousel 34 is slotted to allow vessels to be transferred on/off the carousel horizontally.
When vessels 36 are on the incubation carousel 34, they move inside a thermal incubation trough, which guides the vessels as they travel around the carousel, and keeps them at a steady temperature. The incubation trough is aluminum and heated via a resistive element. A thermistor senses the metal temperature nearest the vessels.
The incubation carousel operation is asynchronous; i.e., it can position any of 45 vessels to any of three locations as noted above at any time. This provides flexiblity in assay formats and complete random access.
The processing carousel 32 contains 15 discrete positions, and is situated concentric inside the incubation carousel. The processing carousel allows the vessels to be presented for: 1) magnetic separation, 2) aspirate/wash, 3) re-suspension mixing, and 4) transfer on/off the processing carousel to the incubation carousel. The processing carousel 32 may be about 7 inches in diameter.
The processing carousel 32 is driven by the drive means 31, by the same as the incubation carousel. Similar to the incubation carousel, the processing carousel is slotted to allow vessels to be transferred on/off. The vessels are held in place on the carousel with spring clips.
Unlike the incubation carousel, the sequencing of the processing carousel is synchronous or repetitive. Whenever reaction vessels 36 are present on the carousel, the carousel will index in a rote manner, advancing each vessel through a series of separate-wash-mix steps.
Generally, repetitive operation enhances throughput, but places certain restrictions on assay formats and random access capability. Since 15 reaction vessels can occupy the carousel and process simultaneously, throughput is enhanced. However, since the processing carousel operates independent of the incubation carousel, flexible assay formats and complete random access processing is still achieved.
The sensitivity requirements of some heterogeneous assays demand that the processing station efficiency must be very high. This invention permits repeated washes of each reaction vessel, in order to ensure the desired near-zero background levels. Nominally, each assay has a total of 4 separate/wash sequences.
A common transfer station 38, which accesses both carousels 32 and 34, is provided for transferring reaction vessels 36 between the two carousels 32 and 34 and for removing reaction vessels 36 from the sample processing module 30 and passing them into a suitable waste disposal, not shown.
The transfer station 38 (FIG. 2), which may be of conventional design, is used to transfer reaction vessels 36 to/from the processing carousel and to load/unload vessels from the incubation carousel 34. All vessel transfers are done in the horizontal plane only, by simply sliding the vessels along their path on a slider 39. The slider 39 is driven via a stepper motor, (not shown), and can locate the vessels anywhere along the transfer station 38, i.e., over either of carousels 32 or 34. An encoder is used to verify positioning of the slider. As the design must allow for new vessels to come in and old ones to clear, a `T` track 46 is employed. A solenoid driven gate (not shown) is closed to allow new vessels to be loaded.
New vessels are routed to the vessel transfer station 38 via the feedtrack 44. A drive wheel 48, located at the end of the feedtrack 44 near the transfer station, is used to provide positive drive of a stack of vessels (not shown) when the system is loading a new vessel into position for transfer onto the incubation carousel 34.
Used vessels are routed to the waste container via a plastic chute 41 attached to the underside of the transfer station, beneath a hole in the exit track (not shown).
A second liquid probe 40 is rotatably mounted above cuvette carousel 16 and is adapted to draw reagent liquid from an appropriate reagent liquid cartridge 20 and deposit such reagent liquid in a predetermined reaction vessel 36 in the incubation carousel 34. Sample liquid probe 28 is also adapted (1) to draw sample liquid from a reaction vessel 36 after the sample liquid has undergone the scheduled pre-assay operations and (2) to deposit sample liquid within a predetermined cuvette 18 for further processing and measurement.
In accordance with this invention, sample processing devicps, or stations 42 (FIG. 1), are positioned at selected circumferential locations about the processing carousel 32 such that they can access reaction vessels 36. It will be recalled the processing carousel 32 is concentrically mounted with the incubating carousel 34, radially outside of the processing carousel 32 (depicted in FIG. 1 as inside for the sake of clarity).
These stations are adapted to provide for mixing together of the sample liquid and the reagent liquid contained in a reaction vessel 36, for washing the sample liquid and the reagent liquid contained in a reaction vessel 36, and for magnetic separation of tagged magnetic particles from free tags or reagent liquid contained in a pre-assay reaction vessel 36.
Two wash stations W1 and W2 (FIG. 2) are used to aspirate away unbound sample and/or reagent from reaction vessels, and possibly replenish the vessel with a wash buffer for subsequent steps.
The wash station module comprises a casting that holds two dual wash probes (W1 & W2), allowing two vessels to be washed concurrently. The probes are spring loaded, which ensures reliable contact with the bottom of each vessel for complete aspiration. The probes operate on adjacent vessels; if only one vessel is present, only one probe is aspirated/dispensed. The probes are positioned up/down via a stepper motor. The position is verified using a home sensor after each operation.
There are two mix stations M1 and M2 (FIG. 2). They are used to re-suspend the separated magnetic particles in the wash buffer after each wash. The mixer employs a vortex external mixer design, which avoids any contamination with the sample/reagents while mixing. Mixing station M preferably impart a vortexing mixing action to reaction vessels 36 as is a usual practice in the manipulation of samples in chemical laboratories. Devices are available for this purpose and preferably comprise an externally mounted disc which is placed against the bottom of the reaction vessels and eccentrically rotated.
Design of the mix station is conventional, for example, as described in U.S. Pat. No. 4,848,917, Benin et al. assigned to the assignee of the present invention. In a preferred embodiment, external contact is made with the vessel(s) using a mixing pad to engage the vessel bottom tips. The vessel is then wobbled in an eccentric motion, causing the vortex mix. The mixing pad is normally recessed about 0.050 inches below the vessel bottoms, so that the vessel tips will clear while the wash carousel is advancing them between stations. When vessels are in position for a mix, the mixing pad is elevated to make contact with the vessels. The elevation is achieved via swing-out cams, which engage when the mix motor is energized and reaches a certain speed. A sensor is used to detect that the mix pad is properly engaged.
As with the wash stations, the mix stations M1 and M2 can operate on two vessels concurrently. Normally, two adjacent vessels are mixed simultaneously; however, the mixer is capable of mixing either of the two adjacent vessels if the other one is missing.
The separation stations S1 to S9 (FIG. 2) as conventional and typically include magnets positioned adjacent the locations of the reaction vessels 36 for attracting the magnetic solid support particles (such as those described in U.S. Pat. No. 5,104,808) to the walls of the reaction vessel such that unbound material may be aspirated.
FIG. 2, as noted, shows various stationary processing stations (described above) disposed contiguous the processing carousel 32. The drive means 31 for controlling movement of carousels 32 and 34 is conventionally controlled by a controlling unit, preferably a microprocessor based central processing unit (CPU), housed in the analyzer 10 to move the vessels index-stepwise to each processing station 42 where at pre-assay processing occurs, as described below. The control is provided by software, typically like that used on the Dimension� clinical chemistry analyzer and is widely used by those skilled in the art of computer-based electromechanical control programming. The rotating means are preferably commercially available stepper motor mechanisms.
In accordance with the present invention, the processing carousel 32 is indexed to successive processing locations or stations 42 capable of performing various pre-assay operation. The samples at each station are subjected to various pre-assay operations for a constant time period. FIG. 2 shows the processing carousel 32 preferably associated with pre-assay treatment stations distributed as follows: ten separation stations (S1 . . . S10), two wash stations (W1, W2), and two mix stations (M1, M2), and the transfer station 38.
The important time-templating features of the processing carousel 32 of the present invention are described next in detail. These are implemented by operating software programs which will be described in conjunction with the FIG. 3. It has been discovered that if a particular relationship is established between the number and location of processing stations on processing carousel 32 and the sequence at which reaction vessels 36 are repetitively indexed to processing stations 42 is maintained, then it is possible to significantly increase the efficiency of pre-assay processing of samples undergoing heterogeneous assays. These samples may require either a first reagent addition, sample-support separation, sample mix and sample wash and/or a second reagent addition, a second sample-support separation, a second sample mix and a second sample wash.
In order to achieve the pre-assay protocols associated with these alternate pre-assay requirements, it has been discovered that one can use repetitive sequences or patterns of movement for each of the reaction vessels 36 to the several processing stations 42, i.e., S, W, and M.
In accordance with this invention, rather than index or sequence the processing carousel 32 one position at a time, a novel technique is used to advance the vessels unique segments or groups of index positions at a time. The processing carousel 32 has 15 stations, hence there are 15 indexes or positions to index the carousel for a complete revolution. The advancing is always in the same direction and alternates between incrementing groups of +6 indexes or positions and +7 indexes or positions of the processing wheel (FIGS. 2 and 3). Applying this sequence to the processing carousel 32, it can be seen that a reaction vessel 36 entering at "X", the transfer station, and advancing a total of 30 groups of indexes, would transition through all the stations in this pattern:
TABLE 1______________________________________X-S-S-S-S-S-W1-X-M1 (first wash)-S-S-S-S-W1-S-M1 (second wash) -S-S-S-S-W2-S-M2 (third wash) -S-S-S-S-W2-S-M2-X (fourth wash)______________________________________
This sequence provides the needed four separate/wash/remix steps using 30 groups of indexes. Simultaneous assays would use all four washes consecutively. Sequential assays would use the 1st separation/wash steps after the first incubation, and the 2nd, 3rd, and 4th separation/wash steps after the second incubation.
As depicated in Table 1, above, starting from the point of entry at the transfer station, each and every reaction vessel 36 in processing carousel 32 undergoes a first indexing segment or STEP 1 in which the processing carousel 32 is indexed counter-clockwise past five intervening processing stations without stopping to the sixth-next processing station S1. Thus, a first reaction vessel at station X is transferred counter-clockwise by a synchronous movement of the inner carousel 32, past five intervening processing stations to the seventh processing station S1. After the same constant predetermined time of operation, the processing carousel 32 is indexed repetitively counter-clockwise past six intervening processing stations without stopping, to the seventh-next processing station S2. This repetitive pattern of movement of indexing forward first to the sixth-next processing station, followed by sample treatment for a constant predetermined time of operation, and then indexing forward to the seventh-next processing station is repeated with the indexing always in the same direction, forward or counter-clockwise as seen from above, without stopping regardless of the assay to be performed. A reaction vessel 36 on processing carousel 32 thereby experiences a first rotational movement which comprises six carousel step-indexed movements "forward", each indexed segment movement followed by a stopped time at the aligned processing station Mn, Sn, or Wn as indicated for a constant time amount of pre-assay sample treatment. This repetitive pattern of six-seven index segments is repeated as explained below when needed to perform five separate treatments, i.e., single wash and single mix pre-assay processing treatments as in the instance of a "single-reagent" heterogeneous assay. In the instance of a so-called "two-reagent" heterogeneous assay, the reaction vessel 36 may be removed from the processing carousel 32 for additional reagent treatment, as explained below and then re-placed on the processing carousel 32.
Applying this sequence to the processing carousel 32 arrangement as shown in FIG. 2, it can be seen that a vessel entering processing carousel 32 from the transfer station 38, and indexing a total of 30 index segments would make two complete revolutions around the carousel, and would transition through all the required stations before being presented to the transfer station 38 for transfer to the incubation carousel 34 where sample aspiration may occur. This sequence provides four separate wash cycles of separate, wash, and mix cycles using 30 index segments. In the case of a sequential assay, after the first wash cycle is completed, the reaction vessel is located at the transfer station. Certain sequential assays require an additional reagent addition and incubation period after the initial transfer to incubation carousel 34 and thereafter are transferred back onto processing carousel 32 to complete the separation process, again processing through the second, third and fourth wash cycles as needed.
This increased throughput is made possible by using a repetitive movement of the processing carousel 32, in which each of the reaction vessels 36 on the processing carousel 32 are presented to processing stations Sn, Mn and Wn in an ordered manner, each vessel 36 being processed by the station where it is moved during the synchronous movement of the processing carousel 32, each vessel furthermore being processed by the different devices Sn, Mn, and Wn for a same constant amount of time.
The timing sequence for these wash cycles is shown in FIG. 3 and the timing sequences is calculated by the CPU of the analyzer 10. Without regard to the express times at the several processing stations 42, the repetitive sequence making up the several wash cycles may be better understood with reference to Table 2. The appropriate choice of the number of processing stations and devices, in combination with assigning to each processing station a same constant amount of processing time regardless of the capability of the station enables the throughput of processing carousel 32 to exceed normal expectations.
Furthermore, in accordance with the present invention, is the ability to handle a plurality of reaction vessels, up to a maximum of fourteen, and present each one of the reaction vessels to the required resource in the required order, the number of resource stations being equal to fifteen stations.
TABLE 2______________________________________First Wash Cycle Step 1 2 3 4 5 6 7 8______________________________________ Processing Positions +6 +7 +6 +7 +6 +7 +6 +7 Stations 42 S1 S2 S3 S4 S5 W1 X M1______________________________________Second Wash Cycle Step 9 10 11 12 13 14 15______________________________________ Processing Positions +6 +7 +6 +7 +6 +7 +6 Station 42 S2 S6 S4 S7 W1 S/D M1______________________________________Third Wash Cycle Step 16 17 18 19 20 21 22______________________________________ Processing Positions +7 +6 +7 +6 +7 +6 +7 Station 42 S8 S6 S9 S7 W2 S/D M2______________________________________Fourth Wash Cycle Step 23 24 25 26 27 28 29 30______________________________________ Processing Positions +6 +7 +6 +7 +6 +7 +6 +7 Station 42 S8 S1 S9 S3 W2 S5 M2 X______________________________________
A "dummy station" D is located as shown at the first counter-clockwise location next adjacent the transfer station 38. It is labeled S/D because it has a separation magnet to maintain any magnetic particles in reaction vessels 36 at that station clustered. The presence of and positioning of "dummy station" D enables the use of a repetitive pattern chosen to present each one of the reaction vessels 36 to the required processing station in the required order. As a result of the particular distribution of pre-assay processing stations in a circular pattern, coupled with the particular movement pattern being broken into four cycles, each reaction vessel is sequentially positioned at sub-groups of separate, wash, mix, stations, allowing the ancillary devices (motors, stirring pads, drains, etc.) that support the action of the two wash probes and the mixers to be ganged together for a compact design.
This technique provides:
reduced carryover potential, as the W1 wash station is used for first 2 washes, and the W2 station for final 2 washes,
the wash stations and mixers are located adjacent one another, allowing the 2 wash probes and mixers to be ganged together for a compact design,
increased throughput when processing sequential assay formats that require a 1st phase sample wash and a 2nd phase reagent wash.
In addition to achieving the desired result of positioning like processing stations proximate one another, so as to achieve maximum utilization of supporting devices (motors, pumps, common stirring pad, drains, etc.), once the processing carousel 32 is totally full of reaction vessels 36, for example, as would occur during high volume processing, all vessels are being actively used in either a separate or mix station, except for those vessels positioned at either a X or D position. As many as 13 other reaction vessels 36 may be at different stages in the pre-assay treatment positions afforded by the processing carousel 32 and still allow for an additional reaction vessel to be entered onto the carousel, requiring only that the transfer station X be vacant.
The present invention uses a novel positioning and advancement of the reaction vessels 36 to provide increased throughput when processing heterogeneous sequential assay formats which require an initial wash cycle followed by a reagent addition to accomplish tagging of the antibody and then a final wash cycle. A surprising result of this apparatus is the ability to accomplish high throughput for competitive assay formats which require a first and second incubation. Throughput is a function of the assay requirements, the available resources to service these requirements, and how well the resources are scheduled. All of these must be balanced. It has been found that the present invention provides a proper balance of all of these essential elements to provide an optimum throughput, regardless of whether the assay is simultaneous or sequential.
When fully loaded with a maximum of 15 reaction vessels 36, all vessels may be sequentially stepped through the required stages of separation, wash, and mix in an almost continuous fashion without interrupting the sequential stepping motion of processing carousel 32. This feature has been found to provide a significant reduction in processing time over that which would have been required if the pre-assay steps were handled in the more conventional pattern of completing each reaction vessel's 36n pre-assay processing before starting another and/or of ganging together a small number of reaction vessels for pre-assay treatment.
In a particular embodiment, the pre-assay processing carousel 32 of the present invention is designed and depicted in FIG. 3 to process heterogeneous assays using an index time for each step of the processing carousel 32 of 10.8 sec. Thus for the four wash cycles each including the stations 42 of S. W. and M for the time indicated at each station of a sequential heterogeneous assay, the time required is 30�10.8 or 324 seconds. Simultaneous assays use the four wash cycles consecutively. Sequential assays use the first wash cycle, then transfer off for incubation, then transfer back for the second, third, and fourth wash cycles.
Because of the sensitivity requirements of modern heterogeneous assays, it is very important that washing be done in a manner that produces very high efficiency as well as minimizing carry-over between vessels. The present invention produces near-zero background levels. This is done by performing two fairly "gross" washes by station W1 at steps 6 and 13. This is followed by a third wash in station W2, and a final fourth wash in station W2 to reduce the final background level to a lower value. As the term is used herein, "magnetic particles" or simply "particles responsive to a magnetic field" may be any of those known in the art. They are preferably ferromagnetic and have a small residual magnetism so that little clumping occurs in the absence of a magnetic field. Preferably magnetic particles of the type described by Lau et al. in U.S. Pat. No. 4,661,408, are employed. The separation stations S thereby separate the bound and free phases in order for the mixing process to proceed.
It is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the invention and that other modifications may be employed which are still within the scope of the invention. Accordingly, the present invention is not limited to those embodiments precisely shown and described in the specification but only by the following claims.
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|Jun 1, 1998
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Series Sponsors:
2017 Dirty Dozen 12hr
Antonio Garza's blog on the Dirty Dozen mtn bike ra...View
It's the little things
I wanted to send an email to say thank you to Terra Firma Racing. I recently participated in the Bluebonnet AR at the XXX Ranch. First of all, the venue...View
Reveille Peak 100 race recap by Cooper Sellers
Check out the race recap by Cooper Sellers of our recent Reveille Peak ...View
Paul Mitchell XTERRA Terra Firma Trail Run: Challenge yourself to a 5K or 15K trail run with plenty of natural obstacles including creek crossings, ravines, and hills along the way. This race is at night, so you will need to bring a headlamp or flashlight to light your way. You will be following a course of reflective ribbon. This race is part of the XTERRA Trail Running series.
Male & Female in the following:
<9, 10-14, 15-19, 20-24, 25-29, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80+, Physically Challenged
Shot Glass Souvenir to all finishers
Race shirt guaranteed to those preregistered by September 5th, 2015.
Medals to Top 3 in each Category, 5-year XTERRA increments from above categories
Overall Male & Female in 5K & 15K
Overall Male & Female Master's (40+) in 5K & 15K
5K Trail Run ($35 until Sept. 5th, $45 Sept. 6th - race day)
15K Trail Run ($50 until Sept. 5th, $60 Sept. 6th - race day)
All racers registered by Sept. 5th are guaranteed a race shirt! If registering during last 2 weeks, no guarantee.
*There is a gate fee per person (racers and spectators) at the ranch payable to the landowner in cash upon arrival
$10 Day Use Fee single day only
$15 Two Days and includes camping if you stay overnight
Free - Kids 12 and under
SCHEDULE OF EVENTS:: (Check in at the race site):
Saturday, Sept 19th, 6:30-7:30pm: Race checkin and packet pickup for XTERRA Trail Run
Saturday, Sept 19th, 7:45pm: Night XTERRA Trail Run Start (5k & 15k) (Bring Flashlight or Headlamp)
Saturday, Sept 19th, 6:30-7:30am: Race checkin and packet pickup for Duathlon at race site
Saturday, Sept 19th, 8:00am: Duathlon Race start
Saturday, Sept 19th, 11:00am: Duathlon Awards
Saturday, Sept 19th, 12:00-4:00pm: Tough Cross Endurance Cyclo-Cross Race (Kodiak Tough Website for details)
Sunday, Sept 20th, 9:00am-1:00pm: Touch Cross Traditional Cross Races (Kodiak Tough Website for details)
This race is part of the 2016 XTERRA Trail Running series. You will earn points in the XTERRA Trail Running series: Click on Series to learn more about it.
Refund Policy:
No refunds under any circumstances. Wait! Well maybe. We at Terra Firma understand that things change, sometimes out of your control and we never want to rip anyone off. But please understand that we make a considerable investment in shirts, awards, dumpsters, porta potties, land use fees and a host of other expenses to put a race on. We know your one fee doesn't effect this number, but if we don't have a policy and stick to it, where do we ever draw the line?
We think we've come up with a pretty liberal policy and hope you agree:
Warda is on Highway 77 halfway between
La Grange (ten miles south) and Giddings (ten miles north)
Here is the link to the direction on the Bluff Creek Ranch Website:
|Apycom jQuery MenusTerra Firma Racing LLC | 214.244.1263

subset: commoncrawl


text:
Metal Roofers in Hammonton, NJ
Find metal roofing in Hammonton, NJ with Hometown. We verify credentials and gather trusted reviews on local roofers that have experience in metal roof application. Roofing estimates on copper, steel roofing, and aluminum roofing are free of charge. Contact a roofer below for more information.
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Metal roofs get coated with protective paints and enamels designed to prevent rust and corrosion. Regular maintenance (i.e., once per year) can help extend the protection of these coatings. Certain chemicals – fertilizers, animal waste, acid rain – can damage metal roofing over time. Pine needles left to decompose can also cause damage to metal roofs because of its acidic nature.
The good news is that it's easy to maintain a metal roof. Just spray it down with fresh water using a garden hose or low-pressure power washer to remove harmful chemicals, pine needles and other debris.
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Various metals are used in manufacturing metal roofing systems and a combination of metals may also be used in some cases. The most common metals include aluminum, steel and copper.
Aluminum is lightweight and an ideal choice if you live near the ocean (seawater can cause damage to some metals). Steel is another popular choice for metal roofing.


text:
It's been almost a month since hardline Islamists overthrew warlords in Somalia's capital Mogadishu. The militia, known as the Supreme Islamic Courts Council, is a grassroots organization.
However, the U.S. says at least one of its leaders has ties to a terrorist organization. The Courts Union now claims authority over all of Somalia, over the protests of the internationally recognized Transitional Federal Government.
The events unfolding thousands of miles away are being closely watched by Somalis in Minnesota.
It's the end of Friday afternoon prayer, and the upstairs mosque on Lake St. in Minneapolis is emptying in a rush. Imam Hassan Mohamud says what's happening in Somalia is constantly on his mind and those in his mosque. Overall he says people are very happy the group, which until recently was called the Islamic Courts Union, has taken control of Mogadishu.
"This now you could call the first time the Islamic courts are trying to bring the Somalis and their faith connected to their Islamic identity," he says. "For that reason they are getting overwhelming support from the people."
Mohamud says Somalis have grown increasingly committed to their faith. It's happening in their homeland and here in Minnesota. He says it's become synonymous with Somali identity.
"I visited one time and I found like every mosque, whether it's small or big mosque, are full," he says. "Every type of prayer you go it's full of people. And here it's the same thing because those people reflect to each other."
Opinion is divided in the Somali community over whether the Courts Union is the best organization to govern their country. But most are simply happy to see peace after 15 years of fighting.
Within the larger Somali community, opinion is divided over whether the Courts Union is the best organization to govern the country. But Ali Galaydh says the majority are simply happy to see peace after 15 years of fighting.
Galaydh served as Somalia's prime minister from 2000 to 2001, and is a professor at the Humphrey Institute at the University of Minnesota.
"This is a most welcome measure," Galaydh says. "And I think that's why the Somalis in Mogadishu and in Somalia and outside, including the ones here in the Twin Cities, will give the benefit of the doubt to the Islamic Courts. But that's exactly what it is, the benefit of the doubt, and not to pass judgment on them."
Galaydh says the Supreme Islamic Courts Council, at its start, represented a variety of viewpoints.
But that's not what's getting the most attention from the international press. Recently, two of the group's leaders publicly claimed authority over the whole of the country. And the new head of the Courts Union, Sheik Hassan Dahir Aweys, is linked to what the U.S. calls a terrorist organization.
Dahir Aweys has also led numerous military campaigns in Somalia, including campaigns against leaders of the current transitional government. He's reportedly a strong believer in Shariah law, which is loosely based on the Koran and can advocate punishments as severe as public beheadings.
Galaydh believes Dahir Aweys will need to consult with other groups, including the weak Transitional Federal Government.
"So Hassan Dahir Aweys was known," Galaydh says. "At the same time, the perception among Somalis is that he's more of a sheik and a leader who is not tied down to his sub-clan, or even his clan."
Galaydh is more worried by the possibility of international troops in Somalia. The African Union is considering lifting its arms embargo on Somalia. The transitional federal government has requested the move, in order to bring in troops to keep the peace. However, Ethiopia and Somalia have often been at war.
"When one hears of lifting the arms embargo and sending international troops, in the minds of Somalis that's sending Ethiopian troops to Somalia," says Galayadh. "And all bets are off then."
All of these delicate complications matter a great deal to Somalis living in Minnesota. Most have family still in the country or in refugee camps. And many, like Somali Mai TV editor Mohamed Issa, want to return to Somalia.
"I want to go back and go there, and help them with the problem they are having," Issa says. "That's the way it is. Everybody has to go back and solve the problem."
Issa isn't opposed to Shariah law. To his mind, Islamic law gives everyone a voice in governance. He hopes to have his say as well.


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The roll call of plein air painters included Tim King, Haidee-Jo Summers, Valerie Pirlot, Karl Terry, David Bachman, Chris Daynes, Tony Dakin, Stuart Fullerton, Roy Connelly, Mike Richardson, Sidney Cardew, Eric (from Seville). I think that's everyone...hope I haven't left anyone off the list!
Venice is always a challenge and real test in terms of drawing, judging tones/values and many other painterly matters. I wanted to try and get to the 'essence' of the subjects and focus on the essentials without getting too distracted by fussy details. I remember discussing this with Tim on one of the Vaporetti, with Haidee and Valerie somewhat amused by our talk of the 'DEADLY fine line' between too much and too little detail. Dangerous sport this painting lark :)
Anyway, to the paintings. I've already started a larger studio version (18x24in) of the study below whilst it's all fresh in my mind! It's useful to have studied the facade of the Basilica a few times now and I can get a feel for the shapes. I love the way you get warm light reflecting up into the arches. The challenge will be to retain the energy of the location study in the studio piece....never easy! It was one of the few clearer days and as a result had a wider tonal range and more vibrant colours.
Another one that seemed to work out OK was this wide view of St Mark's in the fog. A much more muted affair, I really tried hard to keep that 'envelope' of atmosphere in the murky haze. Although the fog obscures many views it can also add a unique atmosphere to certain subjects that you don't see very often. I'm tempted to have a go at a larger one of this one too....why not indeed!


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Credit Advice
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It can hurt, possibly help, or not chang
I can hurt or it may not effect it. The age of your credit history could be affected good or bad depending on how long you have had the card. If your average age goes down it could hurt and visa versa. Also it could hurt by upping your percent of usage of available credit. If currently you have 10k worth of lines of credit and you have 2k owing, then you are 20%. If the card closes and you then only have 9k of avaiable credit using 2k is 22%. Depending on where that falls and if it pushes you up a step in card usage it could bring your score down. Personally I would go and buy something inexpensive on the card and keep it open.
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top necklace
left earrings
right earrings
middle necklace
iphone case
they def. are! I was just thinking about that on the way to work...this is the edgiest spring I can remember in a long time.ReplyDelete
I love triangles, also! And that necklace? So sweet!ReplyDelete
Love the colors on the first necklace and love the scarf!ReplyDelete
Perhaps it's the ethnic vibe we're getting from some of the spring fashions? In any event, tringles are such fun (unless, of ccourse, you're stuck playing them in the band!)
I love the gold earrings and the iPhone case!ReplyDelete
I have several pairs of triangles earrings and love them. Gives us a different geometric from the circle.


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Here's is a thought for a slow vacation week. Congress's approval rating has dipped into the single digits. Anyone with any intellectual honesty – whether liberal or conservative – should agree that we need wholesale change in the ranks of leadership in both parties. Yet the Chamber of [Government-Run] Commerce is prepared to spend $50 million in order to protect the status quo. The Wall | Read More »
Read more here: http://www.redstate.com/2013/12/26/chamber-to-spend-50-million-defending-unpopular-status-quo/ by () Originally posted on


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When you or someone you love is diagnosed with a frightening disease like mesothelioma, contacting an asbestos attorney may not be the first thing on your mind.
However, if you're wondering how you'll pay for your mesothelioma treatment – or what might happen to your family when you're no longer able to work – talking to an asbestos attorney should be one of the first steps you take.
Why is It Important to Contact an Asbestos Attorney?
The statute of limitations, which varies from state to state, limits the period of time within which you can file an asbestos claim. But an asbestos attorney may still be able to recover damages on your behalf even if the common statute of limitations has passed.
What's more, retaining an asbestos attorney and filing a lawsuit may be the only chance you have to get compensation for medical expenses and lost income due to your asbestos exposure. An experienced asbestos law firm like Sokolove Law can fight for your rights and may be able to force the companies responsible for your injuries to cover your pain, suffering, expenses, and losses.
How to Find the Right Asbestos Attorney
When you're looking for an asbestos attorney, it's hard not to get distracted by the lofty promises that many law firms make. However, try to stay focused in your search. To ensure you find an asbestos attorney who will bring you positive results, ask each prospective attorney the following questions:
- How many mesothelioma cases have you handled? What was the primary outcome?
- Who will actually be handling my case?
- Will I be able to call my attorney with questions as needed?
- Will you accept my case on a contingency basis (meaning the law firm will only collect a fee if and when you collect a settlement)?
- Will my claim be handled on an individual basis or bundled with other cases?
Contact Our Experienced Asbestos Attorneys Today
For over 30 years, Sokolove Law has fought tirelessly for the rights of asbestos victims and their families – and we can help you, too. If you've been injured by asbestos exposure, call us at 888-360-4215 today to learn if an asbestos attorney can help you.


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GROWS provides a platform for networking, education, advocacy, and public awareness for senior service professionals in Montgomery County.
If you are a senior, a caregiver, a provider of services to seniors, or someone who is looking for a forum to advocate for seniors, please consider joining GROWS. In addition to helping seniors in need, organizations and agencies can increase awareness about their services and increase their contacts in the community.
Unparalleled Networking
Monthly networking meetings and special events throughout the year provide the opportunity to expand your professional network and grow your referral base.
Legislative Advocacy
GROWS has a solid track record advocating on behalf of seniors at the local and state level.
Professional Development
Programs cover a range of topics, from boosting your marketing abilities to important health topics to the latest in aging research.
Increase awareness about your company by displaying company materials at GROWS events.
Volunteer Opportunities
Join a committee or help with a GROWS event to further expand your professional network.
GROWS membership provides true "bang for the buck!" Small businesses, independent contractors, major corporations -- they are all members of GROWS because GROWS works for their business!


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- Released: Jul 18, 2002
- Sound: 9
- Lyrics: 8
- Overall Impression: 9
Users' score:
(5 votes)
Sound — 9
The Mad Capsule Markets are a Japanese band who play some of the most inventive music in the world at the moment, this live album captures their biggest hits live. There music is a kind of dance-metal hybrid with occasional rapping thrown in, and it sounds awesome. While the guitar and bass are brilliant, it is the addition of electric beats with the drumming that really makes it sound phanomenal, the use of other electric and dj effects works well. The singing switches from English to Japanese in many of the songs which can be a bit annoying for English speaking and Japanese speaking people alike.
Lyrics — 8
As with a lot of the music that comes from the far-east, the lyrics are a lot more complicated than anything over here, Translation: they are insane! for example in 'Kumo' the verse reads; "Hallucinaion and illusion. There is no such thing that reflects there, the next pioneer who is on earth, awakening light, It's released at this moment." Rapper Kyono is very talented indeed while bass-toting singer and songwriter Takeshi Ueda has a brilliant voice for sing-along choruses.
Overall Impression — 9
This is a great album for people who havent heard much from MCM as it contains most of their hits. 'Good Girl' is one of my favourite songs as it has a great poppy hook and sing along choruses while being heavy at the same time. 'Fly High' is another great track with similar qualities while their biggest hit 'Pulse' (it also appears on a Tony Hawks soundtrack) sounds absolutely huge! Other standout tracks include 'Gaga Life', 'Chaos Step' and 'Island'.


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Banks, building societies, broker-dealers and CCPs run liquidity risk as part of their provision of critical financial services to the real economy.
In such circumstances, central banks are well placed, as the monopoly suppliers of the most liquid means of payment — banknotes and central bank reserves — to act as backstop providers of liquidity to solvent banks: so-called 'liquidity insurance'.In its liquidity insurance role, the Bank stands ready to provide solvent counterparties with highly liquid assets, in sufficient size and at an appropriate term, in exchange for a wide range of collateral assets of good credit quality but lower market liquidity. The terms of the Bank's liquidity insurance facilities are set to ensure counterparties have the incentive to manage their liquidity primarily through private markets in normal times.Banks seeking to exchange less liquid for more liquid assets have access to three facilities, each with a different purpose:
The Bank also offers some liquidity insurance in the normal course of implementing monetary policy. Reserves averaging and OSFs are both designed to keep market interest rates in line with Bank Rate. But they both allow banks to absorb some liquidity shocks by varying their position at the Bank from day to day at little or no cost.
Red Book - Liquidity Insurance Developments in the Bank's approach to liquidity insurance Managing Liquidity in the System: The Bank's Liquidity Insurance Operations - Speech by Paul Fisher News Release, 30 September 2010


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WASHINGTON, Nov. 14 (UPI) -- U.S. President Barack Obama has authorized more aggressive tactics to defend government and private computer networks from attack, administration sources said.
Citing sources it did not name, The Washington Post reported Wednesday the president signed a secret directive in mid-October, setting new standards for federal agencies dealing with the threat of cyberattacks.
Presidential Policy Directive 20 draws a distinction between network defense and cyber operations outside of networks "for what might be called defensive purposes," a senior administration official told the newspaper.
The directive, which updates policy established in 2004, is part of a broader Obama administration effort to deal with cyberthreats, the Post reported.
"It should enable people to arrive at more effective decisions," a second senior administration official told the newspaper.
The White House is also working on an executive order to protect private networks from attack and legislation to that effect is under consideration in Congress, the Post said.
James A. Lewis, a cyber expert at the Center for Strategic and International Studies, said the new policy directive shows the United States is "not going to be a bystander anymore to cyberattacks."


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American Le Mans Series Long Beach – C6.R Photo Gallery
Power Automedia's own Mark Gearhart has been shooting the Long Beach Grand Prix for a decade, and this weekend he's sending us back some awesome shots of the ALMS Corvettes in action. Please enjoy this photo gallery, and check back as we update with more!
Friday Qualifying:
Friday Practice:


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Tyler County authorities Saturday released the names of two men arrested in the case of the massive pot farm found in Tyler County Thursday.
A sheriff's office spokesperson says both men arrested Thursday are named Mario Vasquez. Both men are being held in the Tyler County Jail on $150,000 bond for charges of possession of marijuana with intent to manufacture and deliver.
Tyler County Chief Deputy Clint Sturrock tells 12News he anticipates making more arrests soon.
The plantation was discovered just east of Hillister in southern Tyler County.
Authorities say 4,700 plants were found off of CR 4380 with some plants grown to more that eight feet high.


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Glendoveer Golf Course, East Course
33 Reviews
- 14015 NE Glisan St, Portland, OR 97230
- (503) 253-7507
- www.golfglendoveer.com
The East Course at Glendoveer Golf Course is an 18-hole regulation length golf course in Portland, Oregon. This medium-length layout features 4 sets of teeboxes for the enjoyment of golfers of all skill levels. There is another course on this same property, the West Course. Online tee times may be available at Glendoveer Golf Course or at nearby golf courses, usually offered at a discount from the normal rate.
Even though the data is mostly accurate, in some cases there will be inaccuracies. If you come upon any wrong facts, please help us fix it.
Tee Times for Glendoveer Golf Course (and other courses)
4 Stars (18 Reviews) - Last updated on July 15, 2014
There is a Yelp.com page for "Glendoveer Golf Course - Northeast Portland - Portland, OR"
The score on Yelp is 4 out of 5. That score is an average of 18 ratings, and it is rounded to the nearest 0.5. Also note that sometimes Yelp excludes from that score any reviews that that it classifies as "not recommended."
Read reviews on Yelp.com
4 Stars (15 Reviews) - Last updated on July 15, 2014
On the Google+ page for "Glendoveer Golf Course", they have an average rating of 4/5, and they have a total of 15
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Comparisons between a TV show's various seasons are inevitable -- just try to find a "Buffy the Vampire Slayer" viewer or a fan of "The Wire" who doesn't have a favourite season. But in the case of NBC's "Smash," comparing the show's first and second seasons has become a question of which showrunner is most responsible for the series' descent into darkness.
See also: Is 'Smash' any better this season?
After creator and former showrunner Theresa Rebeck was dismissed from the series, "Smash" staffers believed they'd be given a second chance, an opportunity to redeem the show from weeks of critical panning and behind-the-scenes madness. Unfortunately for "Smash" and its staff, ratings have only declined in Season 2.
As a result, Rebeck has finally spoken up, a choice she opted out of in January when Buzzfeed ran its takedown of "Smash," which painted Rebeck in a less-than-flattering light -- or, more accurately, as a control freak unable to handle the stress of the job. In a series of emails to Buzzfeed's Kate Arthur, Rebeck defends herself against the claims, posing an interesting question:
"If in fact Theresa Rebeck was the problem with Smash and the train wreck it became," Rebeck wrote. "Wouldn't things have gotten better -- rather than drastically worse -- once she left?"
She continued: "In any case I would like to state that your version of events is so wildly untrue, and also so unauthenticated, I was surprised to see it is still on the Buzzfeed website. Might I propose that in the interest of fairness, you now take it down? If the interest of fairness is not too distant a memory for you."
Yikes. Write Kate Aurthur immediately responded, offering to talk to Rebeck about the claims, and alerting her that she'd publish the email in full "without any commentary, other than to point out that 'Smash' has fared poorly in its second season in the ratings."
That didn't exactly sit well with Rebeck, who was unimpressed with Aurthur's intention to publish the emails, but continued to argue that "most media reports would agree that the second season is a complete disaster, and that the troubles with a once promising show go far beyond faring poorly in the ratings."
You can read the complete exchange here.
See also: TV shows on the bubble: Will they be back next season?
While Rebeck is obviously unhappy with the way January's Buzzfeed piece painted her, does she still have a point? Considering "Smash" continues to flail in terms of ratings (especially now that NBC has dumped it into a Saturday night time slot), does that indicate the problem is bigger than who's in charge?
It may be more a question of taste: "Smash's" first and second seasons are like night and day in terms of plot development and characters (we miss you, Uma Thurman!), and while the second season may have roped in new viewers through its new production numbers and characters, it may have lost those who grew to love the madness of "Smash" Season 1. Arguably, it's a trade off.
And if "Smash" does magically get renewed for a third season (hey, miracles can happen), perhaps the showrunners should focus less on "fixing" the show, and more on combining the best parts of Seasons 1 and 2 -- beginning with bringing back Debra Messing's scarves. Pretty please?
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What to Do If Your Pet Eats Grass
Does your pet regard your lawn as the perfect place to snack? Eating grass may not seem very appetizing to you, but your pet doesn't share your disdain. In fact, both dogs and cats enjoy eating a ...View Article
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PET | TAO Holistic Pet Products, co-founded by Dr. Casey Damron, is a pet food and treat line combining Eastern food therapy and Western nutritional science. Using the guiding principles of Yin/Yang and the Five-Element Theory, PET | TAO offers energetically balanced canned dog and cat food as well as freeze-dried treats.
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If you live in Fairview or the surrounding area and need a trusted veterinarian to care for your pets – look no further. Dr. Casey Damron is a licensed TN veterinarian, treating all types of pets. Your pets' health and wellbeing are very important to us, and we take every possible measure to give your animals the care they deserve.
White Oak Animal Hospital is a full service animal hospital and welcomes both emergency treatment cases as well as pet patients in need of routine medical, surgical, and dental care. Dr. Casey Damron has years of experience treating serious conditions and offering regular pet wellness care. Beyond first rate pet care, we make our clinic comfortable, kid-friendly, and calm, so your pet can relax in the waiting room and look forward to meeting our Fairview veterinarian.
We are happy to offer a number of resources that enable you to learn about how to take better care of your pets. Please feel free to browse our site, particularly the informational articles. The best veterinary care for animals is ongoing nutrition and problem prevention, so becoming knowledgeable about preventative pet care is essential to the ongoing success of your animal's health. If you have any questions, call 615-799-7981 or email us and we'll promptly get back to you. Our Fairview veterinarian office is very easy to get to -- and you can find directions on our Contact Us page! We also welcome you to subscribe to our newsletter, which is created especially for Fairview pet owners.
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Brad Meester is the senior member of the Jaguars, but he's not ready to retire even though he's finishing his 13th season this year.
Meester said Monday he will return if the Jaguars want him back next year. He said he's in a "wait and see'' mood to see whether the Jaguars want him to return after they do their post-season evaluation.
Meester, who is usually given Wednesdays off from practice, said, "I feel as good as I have in quite a while.''
"I would love to be back,'' he said.
Meester was drafted in the second round in 2000 and has spent his entire career with the Jaguars, which is rare in this era of free agency.
Only three other players besides Meester, have been with the team since before 2006. Cornerback Rashean Mathis was drafted in 2003 and kicker Josh Scobee and fullback Greg Jones were drafted in 2004.