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|Número de publicación
|Tipo de publicación
|Número de solicitud
|Fecha de publicación
|24 Oct 2006
|Fecha de presentación
|19 Dic 2002
|Fecha de prioridad
|19 Dic 2002
|También publicado como
|Número de publicación
|David P. Yavorsky, Jonathan Royce, Matthew Alexander Tomasko, Ven Anantha Raman
|Cesionario original
|Millipore Corporation
|Exportar cita
|BiBTeX, EndNote, RefMan
|Citas de patentes (23), Otras citas (1), Citada por (25), Clasificaciones (18), Eventos legales (3)
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet
In general, the present invention is directed to a deep gradient-density filter device and, in particular, to a deep gradient-density filter device comprising layers of filtration material well-suited for the primary or secondary clarification of manufactured biopharmaceutical fluids.
Depth filters (e.g., gradient-density depth filters) achieve filtration within the depth of the filter material. A common class of such filters are those that comprise a random matrix of fibers, bonded (or otherwise fixed) to form a complex, tortuous maze of flow channels. Particle separation in these filters generally results from entrapment by, or adsorption to, the fiber matrix. In gradient-density depth filters, several fiber-based filter materials (e.g., in mat or pad format) of different average nominal pore size are arranged sequentially in progressively increasing retentiveness.
Current technologies relative to depth filtration, particularly for applications requiring the removal of submicron particles, are limited to comparatively thin layer(s) of filtration material. With respect to common biopharmaceutical applications, the two most popular clarification fiber-based depth filter materials are dry-laid, gradient density, synthetic fiber pads and wet-laid, cellulose fiber sheets (with or without embedded inorganic filter aids). In either case, the overall filter material depth (or thickness) is invariably restricted to less than 10 millimeters (0.394 inches), primarily due to the high hydraulic resistance (i.e., native pressure drop per unit of fluid flow per unit area) of the filter material. Accordingly, to assure an acceptable rapid rate of fluid throughput, fiber-based depth filters based on conventional filter materials and formats are designed with an eye towards maximizing filter surface area.
The conventional predisposition towards use of large surface area filter materials is evident in the wide popularity of the saucer-like lenticular design of conventional fiber-based depthfilters for pharmaceutical and biopharmaceutical fluid clarification processes. See e.g.,
In general, high-area depth filter systems are bulky, prone to poor reliability, and often have high manufacturing costs. An extensive arrangement of media seals is often required to keep the system "tight" and/or non-leaky. And, unlike surface filter media,—such as porous films or membranes which typically can be effectively packaged in a wrapped or pleated cartridge on account of their relative thinness—depth filter media do not tolerate as well the mechanical stresses typical of high surface area cartridge fabrication.
High-area depth filter systems tend also to be slow. It is well known that the filtration performance of a conventional fiber-based depth filter, as measured by filter capacity (i.e., solids loading) or particle retention or both, generally increases as fluid velocity or flux rate decreases. Particle capture—by size and amount—is more generally effective the slower particles travel through a thin filter media. (The mechanism(s) underlying particle capture are not well understood, but likely involve sieving, adsorption, and impingement.) Slow rates (per unit area) also minimize the operating pressures required which at any higher flow rate can be impractical for the high density (low permeability) filter media employed in such applications.
In light of the above, there is a need currently for a compact high-capacity deep gradient-density filter device that is reliable, robust, and easy to manufacture.
In response to the above need, the present invention provides a deep gradient-density filter device having, in comparison to its functional piers, a more "open" range of nominal pore size throughout the depth of its filtration material, which—despite the seemingly greater intrinsic permeability thereof—provides comparably good retentiveness, on account (at least in part) of the unprecedented thickness of said filtration material. By its emphasis on filter thickness, rather than surface area, the present invention is felt to represent a new and pioneering platform for depth filtration, departing markedly from any known, conventional approaches.
In respect of its product aspects, two basic (potentially overlapping) product configurations are envisaged. The first product configuration (i.e., a deep gradient-density filter) is characterized—among other features—by the quantifiably-defined retention capabilities and the collective thickness (i.e., greater than a half-inch) of its filtration material. The second product configuration (i.e., also a deep gradient-density filter) is characterized—among other features—by its incorporation of fibrillated fiber as a primary filtration material.
More particularly, according to the first product configuration, the deep gradient-density filter device is defined herein as having a depth of at least approximately 0.5 inch (1.27 cm.) and capable of filtering a fluid containing a distribution of particles in the range of approximately 25 microns to approximately 0.2 micron, the deep gradient-density filter device comprising in order: (a) a pre-filtration zone comprising layers of filtration material, said pre-filtration zone capable of retaining particles in the range of approximately 25 microns to approximately 1 micron, (b) a primary filtration zone comprising filtration material, said primary filtration zone capable retaining particles in the range of approximately 1 micron to approximately 0.3 micron, and (c) a polishing zone comprising layers of filtration material, said polishing zone capable of retaining particles in the range of approximately 0.3 micron to approximately 0.2 micron. The retention capabilities of the pre-filtration zone, the primary filtration zone, and the polishing zone, as recited in (a), (b), and (c) respectively, are established at a fluid velocity of at least approximately 100 cm/hr and an initial hydraulic permeability of greater than approximately 10 cm/hr/psi.
In the second product configuration, the deep gradient-density filter device is particularly defined herein as comprising in order: a pre-filtration zone comprising layers of filtration material capable of retaining particles within a first size distribution range; a primary filtration zone comprising at least one layer of fibrillated fiber containing material capable of retaining particles within a second size distribution range smaller than said first size distribution range; and a polishing zone comprising layers of filtration material capable of retaining particles within a third size distribution range smaller than said second size distribution range.
Although potential uses of the deep gradient-density filter device are several, in one preferred application, the deep gradient-density filter is used for the clarification of biopharmaceutical fluids leading to the production of pharmaceuticals and therapeutic biological products. In particular, for those biopharmaceuticals produced from genetically modified and/or otherwise manipulated cells, the deep gradient-density filter device is used in the initial harvest of extracellular products (e.g., soluble proteins) following fermentation and/or cloning. The deep gradient-density filter device is implemented to remove essentially all suspended solids in the harvest to a level sufficient for subsequent effective direct sterile filtration or chromatographic processing (e.g., ion exchange, affinity, etc.).
In light of the above, it is a principal object of the present invention to provide a deep gradient-density filter device that is well-suited for the primary or secondary clarification of a manufactured biopharmaceutical fluid, the filter device being robust, inexpensively manufactured and implemented, and having good capacity and good reliability.
It is another object of the present invention to provide a deep gradient-density filter device, the filter material thereof having a thickness of at least a half-inch (in the direction of the primary flow path through said material).
It is another object of the present invention to provide a deep gradient-density filter device having, among its several component layers, a layer of fibrillated fiber material.
It is another object of the present invention to provide a method for filtering a manufactured biopharmaceutical fluid at a comparatively high and steady fluid velocity utilizing a thick deep gradient-density filter device.
For a fuller understanding of the nature and objects of the present invention, the following detailed description should be considered in conjunction with the accompanying drawings.
In general, each of
The present invention provides a deep gradient-density filter device, characterized by its thick stratified arrangement of generally fiber-based filtration material, the device being particularly useful for the clarification of industrially-produced biopharmaceutical fluids. Among its several possible variations, the device can be configured as a compact, easily installable and replaceable unit that is capable of attaining a degree of filtration performance found currently in substantially larger, bulkier, and more costly depth filters.
In one embodiment, illustrated in
Although the use of highly fibrillated fiber (particularly, loose cotton lint) as the primary filtration material in a gradient-density filter device is felt unprecedented in its own right, even in the embodiment where such materials are employed, filtration performance can be improved if configured according to novel structural criteria (cf. thickness) described herein. This structural criteria produces in general a unitary stack T of filtration material that is markedly thicker than any comparable fiber-based depth filter device known to date, and in many instances, resembles a tube or canister (see,
The structure of the deep gradient-density filter device 100 can be described in respect of its "frontal area to volume ratio". The frontal area to volume ratio is calculated by dividing the surface area of the leading layer of filtration material by the total volume occupied by the stack of filtration material.
As used herein, the "leading layer" is the layer first impinged upon when fluid is passed through the deep gradient-density filter device. Since in all practical embodiments the layers of filtration material will be stacked one on top of the other, the surface area of each layer should be substantially the same, and hence, the measurement of surface area can be obtained from virtually any layer within the stack.
The frontal area volume ratio in most typical conventional fiber-based depth filter devices used for biopharmaceutical clarifications is approximately 100–300 m1, providing in many instances the comparably thin structure illustrated in
The advantages offered by the present invention are several, one of which—i.e., linear differential pressure growth—is illustrated in
The graph in
In a device according to the present invention, the particles are admitted more easily into and increasingly captured within the depth of the filter, rather than collecting on the surface. Although pressure will increase during operation, as shown in
While the inventors do not wish to be bound to any theory in explanation of the present invention, it is presently believed that it is the combination of the device's unprecedented structural dimensions and the selection and arrangement of device's filter materials that enables the accomplishment of good particle loading and retention capabilities at unprecedented high fluid velocities and at modest pressure differentials. Whereas under conventional paradigms, filtration efficiency was effected by modulating surface area, the present invention effects filtration efficiency by modulating depth. While the mechanics of particle capture by the thicker inventive structure is not yet well known, it is assumed that—in consideration of heretofore unpracticed filtration conditions—the mechanics are different from prior art mechanisms (e.g., sieving, adsorption, and impingement), and may involve a novel capture mechanism.
As a preferred alternative to frontal area to volume ratio, the inventive deep gradient-density filter device 100 can be more immediately defined in respect simply of its thickness, thickness simply being the reciprocal of said ratio. Thus, it is appropriate to state that the layers of filtration material in a deep gradient-density filter device 100 has a thickness of at least a half-inch. This thickness requirement is true for all embodiments of the deep gradient-density filter device, regardless of the scale of the device.
Although the shape of the deep gradient-density filter device shown in
The collection of filtration media that constitute the deep gradient-density filter device 100 can be assembled together (i.e., held in a fixed predetermined arrangement) with or without the use of an external housing or pressure vessel. Examples of external housings include, but are not limited to cartridges, capsules, boxes, cassettes, columns, and the like; and can be made of variety of materials including, not limited to, stainless steel, high-density polyethylene, aluminum, polyvinyl chloride, polystyrene, polypropylene, glass, and polycarbonate. The housing can be of unitary monolithic form or can comprise several assembled parts. The housing will also be provided with or connectable to at least one fluid inlet and one fluid outlet.
Where a housing is employed, said filtration media will be packed, enclosed, stacked, or otherwise provided therein, together possibly with other elements, such as spacers, screens, fluid distributors, seals, and the like. In general, it is preferred that filtration media be arranged with little or no space between them, in part, to prevent undesirable "liquid hold-up" and to optimize packing density. For biopharmaceutical applications, it has been found that simple stacking the media together so-that they abut under modest mechanical pressure is sufficient.
From the standpoint of simplifying the device 100's structure, and accordingly minimizing its overall manufacturing cost, the filtration media is arranged with no air spaces or other intervening structural element (cf., a spacer) between them. This is not to say the avoidance of such spaces or structures is critical to the practice of the invention. It may be possible to include some of either under certain circumstances without too greatly undermining the functionality of the device. Practitioners may wish to experiment with such alternatives. If spacers or intervening structures are employed, the thicknesses of such are not calculated in determining the total (i.e., summed) thickness of the filtration media.
It is not necessary that an external housing be used in the practice of the present invention under all circumstances. To the contrary, the present inventors find more desirable at this time to construct the filtration media in such a manner as to avoid the need for an external housing. For example, each of the filtration media can be manufactured within an individual framing element, an injection-molded peripheral rim, or like structure, such that when arranged together—for example, between two opposed compression plates—the water-tight fluid pathway needed for the conduct of filtration is formed. In this manner, a practitioner can dispense with obtaining, maintaining, and cleaning a potentially costly housing unit, and instead obtain and replace individual filtration units when needed.
As illustrated in
It will be appreciated that the deep gradient-density filter device 100 is a stepped gradient filter. Stepped filtration is achieved with larger particles accumulating in the upper filtration layer and smaller contaminants progressively accumulating in the subsequent layers. As such, each of the zones are constructed to trap, retain, or otherwise prevent passage of particles within a predetermined size distribution range, the zones being arranged in descending order of size specificity. Thus, the pre-filtration zone 20 is constructed of layer(s) of filtration material that collectively retain particles within a first size distribution range. The primary filtration zone 30 is constructed of layer(s) of filtration material that collectively retains particles within a second size distribution range, this range involving particles that are as a group smaller that those encompassed by the first size distribution range. Finally, the polishing zone 40 is constructed of layer(s) of filtration material that collectively retains particles within a third size distribution range, this range including a particles that are as a group smaller that those encompassed by the second size distribution range.
As used herein, "retention" shall mean "effective particle retention", i.e., greater than 90% of feed particles at a given size range are removed by filter component. Several methods for determining retention are available to those skilled in the art. For example, the use of calibrated or standardized particle suspensions together will particle counters, such as those based on light-scattering or electrical capacitance or impedance.
The distribution ranges for each zones will not in practice be subject to any absolute boundaries. It is the nature of filtration science that a filter (particularly, depth filters) rated for exclusion of a certain distribution of particles, will also pass therethrough a few particles within said distribution. Hence, in certain embodiments of the present invention, the retention distribution ranges of the zones 20, 30, and 40 may overlap at their extreme limits of their respective predefined ranges. A certain amount of such overlap is expected and desirable.
According to its broadest inventive contours, the deep gradient-density filter device 100 is not limited to any preselected numerical retention values of its zones, and subject only to it being a gradient-density filter device and its thickness. However, for biopharmaceutical applications for example, certain specific values have been found to provide desirable results. The deep gradient-density filter device 100 according to this embodiment has a configuration targeted to filter a fluid containing a distribution or particles in the range of approximately 25 microns to approximately 0.2 micron, wherein the materials, the construction of components and sub-components, and the assemblage of zones 20, 30, and 40 enable coverage for selected bands within said range. In particular, the pre-filtration zone 20 provides retention coverage for particles in the range of approximately 25 microns to approximately 1 micron. The primary filtration zone 30 provides retention coverage for particles in the range of approximately 1 micron to approximately 0.3 micron. And finally, the polishing zone provides retention coverage for particles in the range of approximately 0.3 micron to approximately 0.2 micron.
It is possible to obtain the specified retention coverage for each zone by selecting among and utilizing a wide variety of potential materials, construction, and assemblies. Many of these are however unfit and/or impractical. For example, one can provide an extremely retentive zone (i.e., very "tight") comprising several layers of extremely dense filtration material, which under normal operation, would not provide any of the recited coverage. However, by raising the fluid pressure, for example, of said filtration operation to inordinate levels, one may be able to shift its retention values into one of the specified bands of the invention. This is considered inapposite with the objectives of the invention. Hence, in this particular embodiment, in each of the zones 20, 30, and 40, the retention values—as specified above—are established for fluid passing through the zones at a velocity of at least approximately 100 cm/hr and an initial hydraulic permeability of greater than approximately 10 cm/hr/psi.
It is presently believed that the performance of the pre-filtration zone 20 is attributable to the "looseness" of its construction. But for its comparatively thicker profile, the comparatively more "open" structure if used in prior art device would lead to unacceptable "flow through" of the specified particle sizes. This "open" structure however, in the present device enables the construction of a much thicker pre-filtration zone, which provide a path length sufficiently long to assures eventually capture of the specified particles in their transit therethrough, whilst not unreasonably impeding or frustrating good fluid velocity at low pressure.
As with the zones of the deep gradient-density filter device 10, the individual layers of the pre-filtration zone 20 have different densities (i.e., pore sizes) and are stacked in decreasing order of pore sizes. An example of one specific construction of the pre-filtration zone 20 is set forth in
Thickness (in.)
Polypropylene Needlefelt (nominal
~0.10 to ~0.15
As rated.
25 micron rating)
Polypropylene Needlefelt (nominal
~0.10 to ~0.15
As rated.
1 micron rating)
Although the above table illustrates a pre-filtration zone 20 comprising a specific construction, the invention can be practiced with much broader flexibility. Each of layers 22 can be made of the same materials or different. Preferably, however, each layer 22 is made of the same material, and differ only in respect of their pore size ratings. Type of basic materials that can be employed for this purpose include polypropylene, polyester, glass, polyvinylchloride, polycarbonate polytetrafluoroethylene, polyvinylidene fluoride, cellulose, asbestos, nylon, polyethersulfone, and other polymeric (or non-polymeric) materials.
Aside from the basic materials, the filter materials and media disclosed in the following patents can also be considered: U.S. Pat. No. 4,645,567, issued to K. C. Hou et al. on Feb. 24, 1987; U.S. Pat. No. 4,606,824, issued to C. K. Chu et al. on Aug. 19, 1986; U.S. Pat. No. 4,511,473, issued to K. C. Hou on Apr. 16, 1985; K. C. Hou 4,488,969, issued to K. C. Hou on Dec. 18, 1984; U.S. Pat. No. 5,283,106, issued to K. Seller et al. on Feb. 1,1994; U.S. Pat. No. 4,661,255, issued to G. Aumann et al. on Apr. 28, 1987; and U.S. Pat. No. 3,353,682, issued to D. B. Pall et al. on Nov. 21, 1967.
In general, fibrous materials are preferred, because of its versatility, comparative ease of deposition, its strength imparting properties, internal surface to weight ratio, cost, and because fibers can be oriented in various positions and angles. Further, a great variety of diameters of fibers are available, thus making it possible to achieve an assortment of mixtures of different diameter fibers for making fibrous material of a range of porosity, and such fibers can be made of a range of lengths, so as to take advantage of the greater cohesiveness of a layer of long fibers.
Typical fibrous materials include glass and quartz, asbestos, potassium titanate, colloidal aluminum oxide, aluminum silicate, mineral wool, regenerated cellulose, microcrystalline cellulose, polystyrene, polyvinyl chloride, polyvinylidene chloride, polyacrylonitrile, polyethylene, polypropylene, rubber, polymers of terephthalic acid and ethylene glycol, polyamides, casein fibers, zein fibers, cellulose acetate, viscose rayon, hemp jute, linen, cotton, silk, wool, mohair, paper, metallic fibers such as iron, copper, aluminum, stainless steel, brass, silver, and titanium, and clays with acicular lath-like or needle-like particles, such as montmorillonite, sepiolite, palygorskite, and attapulgite clays of this type.
The present invention is not limited to any particular morphology for the layers constituting the pre-filtration zone. Regardless, in its currently preferred embodiment, the material is formed as a pad of non-woven synthetic needle-felt. If polypropylene is used, the polypropylene is preferably "virgin" fiber. In other words, the fibers are essentially free of binders, finishing agents, and other adjuvants which often are added to or coated on polypropylene fibers during or after its formation. "Virgin" polypropylene essentially contains no additives other than those inherent in the synthesis of the polypropylene.
The formation of a filter pad or mat can be effected by various conventional techniques, of which mechanical, aerodynamic, or hydrodynamic web formation is used for natural and synthetic staple fibers and filaments and electrostatic formation for very fine denier fibers.
Spunbonded materials,are preferably formed from melt-spun filaments of thermoplastics, e.g., polyethylene, polypropylene, polyamide, or polyester, which are substantially consolidated by needling, a shrinkage treatment, or by the addition of a binder. Advantage may be realized by the spunbonded process in which the filament-forming polymers are in one operation melt-spun and cooled in air streams, drawn and then directly laid in pad or mat form. Spunbonded non-wovens are often desirable for use as filter material on account of their commercial and qualitative advantages over other non-wovens.
For cellulose-based materials, one method of manufacture commences by first preparing a slurry comprising cellulose fibers, filter additives, and a polymeric thermoset binder. The slurry is vacuum felted and then cured at elevated temperature. The cationic resin, when cured, forms a permanent, interconnected rigid structure. The result is a composite structure having a tortuous structure of flow channels and comprising the filter additives embedded in a cellulose matrix.
The non-wovens used for manufacturing the filter are desirably used in the consolidated state. The materials can be consolidated in any conventional manner, for example by thermal bonding under pressure, in which the material is subjected to a calendering treatment, or by needling, or by thermal bonding using binders, such as hot-melt adhesives, for example in fiber or powder form, in which case the hot-melt adhesive must have a melting point which is lower than that of the fiber material of the web, or the pre-consolidation can be effected using a combination of the aforementioned measures.
The filter material under certain circumstances can benefit by the incorporation of non-fiber additives, i.e., so-called "filter aids". These can be incorporated by use of suitable anionic, cationic, or nonionic binding resins. Examples of additives include, but are not limited to, acid-washed diatomaceous earth, perlite, fumed precipitated silica (for hydrophobic absorption); and activated carbon (for absorption certain homones and pyrogens). In addition, these filter aids as well as conventional chromatographic beads can be incorporated into the porous polymeric films, which can be used as part of one or more zones of the deep gradient-density device 100.
The layers of filtration material used for polishing zone 40 can be made of a variety of materials. The materials may be the same or different amongst the constituent layers, but typically they will be the same, with the layers differing in respect of their porosity. The layers are arranged in decreasing order of porosity. Each layer is approximately 3 to approximately 5 millimeters in thickness. Collectively, the polishing zone 40 is approximately 10 to approximately 20 millimeters in thickness. In a preferred embodiment, each layer is made of wet-laid cellulose containing pad or sheet. An example of specific construction of the polishing zone 40 is set forth in the following table:
Wet-laid pad comprising cellulose
~0.10 to
~140 to ~260
wood pulp and diatomaceous earth
(Manufacturer's Grade 925)*
Wet-laid pad comprising cellulose
~0.10 to
~68 to ~120
wood pulp and diatomaceous earth
(Manufacturer's Grade 935)*
Wet-laid pad comprising cellulose
~0.10 to
~300 to ~560
wood pulp and diatomaceous earth
(Manufacturer's Grade 945)*
Wet-laid pad comprising cellulose
~0.10 to
~140 to ~260
wood pulp and diatomaceous earth
(Manufacturer's Grade 955)*
Wet-laid pad comprising cellulose
~0.10 to
~70 to ~120
wood pulp and diatomaceous earth
(Manufacturer's Grade 965)*
*Available from GusmerCellulo, Inc., of Mountainside, New Jersey 07092.
Other materials that can be used to make the layers of the polishing zone 40 include, in general, many of the same materials, morphologies, and formats listed in respect of the pre-filtration zone, with the exception that the nominal pore size ranges will be substantially smaller. Multiple microporous polymeric membranes can also be utilized.
In certain embodiments, much of the efficacy of the deep gradient-density filter device appears attributed to the manufacture, composition, and configuration of the primary filtration zone 30. In particular, in such embodiments, the primary filtration zone 30 comprises at least one layer of fibrillated fiber-containing material. As in other embodiments, the primary filtration zone 30 is interposed between a pre-filtration zone 20 and a polishing zone 40, each zone configured to retain a specific size distribution range of particles, the zones becoming progressively "tighter" and "less open" from one end of the device to the other.
As used herein "fibrillated fiber" means fiber that is frayed or split along its length or a fiber wherein the ends are split and splayed out, resulting in a multitude of very fine fibrils upon a core fiber. The smaller and thinner fibers or fibrils formed on the core fiber by the fraying or splitting are known as "fibrillae". The fibrillated fibers used in the invention can be formed from fibers that are axially oriented and are less strongly bonded in the transverse direction, such as wood, and certain synthetic fibers described below.
One commonly known fiber that can be fibrillated is wood fiber, which may be fibrillated by controlling the conditions under which the fiber is cut. The fibrillating of wood fiber is explained by Julino Grant in Laboratory Handbook of Pulp and Paper Manufacture, 2nd Edition, 1961, Great Britain, at pp. 147–152.
Another commonly known fiber that can be fibrillated is cotton. Although the present invention is not limited to the use of highly-fibrillated cotton fiber, several embodiments using such fiber have been produced and have been shown to provide good results. Such material is commercially available. For example, high surface area fibrillated cotton fiber can be obtained from GusmerCellulo, Inc., of Mountainside, N.J. 07092. Alternatively, the patent literature provides several disclosures on the process for fibrillating cotton fiber. For example, U.S. Pat. No. 4,761,203, issued to K. D. Vinson on Aug. 2, 1991, discloses fine slurry impaction as a method for mechanically expanding a fiber.
Fibrillated fibers made from synthetic materials are also contemplated for use in the invention. Examples of synthetic fibrillated fibers and methods for making them are disclosed in U.S. Pat. No. 3,097,991, issued to W. A. Miller et al. on Jul. 16, 1963, and U.S. Pat. No. 3,560,318, issued to W. A. Miller et al. on Feb. 2, 1971. Processes for making synthetic fibrillated fibers typically involve the cutting and beating of a fiber of a film of an oriented polymer in, for example, a paper beater or refiner.
Synthetic polymers can be formed into oriented films or fibers by methods known in the art. These typically involve the controlling of the extrusion process and/or a stretching process to orient the polymer in the film or fiber. The oriented fibers or films must be stronger in an axial direction and weaker in a transverse direction (to an extent) to allow fibrillation. Optionally, the polymer can be co-extruded with an incompatible polymer, as is described in the above cited patents, to more readily form a fiber or film that is strong in an axial direction and weak in a transverse direction. This can be accomplished by addition of the incompatible polymer to the polymer melt or the polymer solution or "dope" that is to be extruded. Certain polymers such as poly(imino-1,4-phenyleneiminoterephthaloyl), described below, may be formed in a highly oriented state with long, strong, axial, "grains" separated by weaker amorphous regions, and may not require the use of an incompatible polymer to form fibrillable fibers. The formation of fibrillated fiber from synthetic polymers is well know in the art.
The fibrillated fibers used in the invention should be fibrillated to provide a surface area greater than about 1 square meter per gram, preferably greater than about 10 square meters per gram. The surface area is measured by the B-E-T method described in Brunauer, et al. in J. Am. Chem. Soc., 60, 309 (1938).
In one current configuration, the primary filtration zone 30 comprises a single layer of fibrillated cotton fiber. More particularly, "loose" fibrillated cotton fiber is "sandwiched" between layers of non-woven synthetic fiber pads (front side) and wet-laid cellulosic sheets (back side) that make up the pre-filtration zone 20 and polishing zone 40, respectively. Since, the fibrillated fibers are loose, only a single layer (or stratum) is present. However, technologies are available by which the loose fibers can be fixed into a pad-like structure. For example, one can use binders, preferably sparingly, so as not to reduce the functionally available surface area of the fibers. Alternatively, the fibers can be packed within an enclosed mesh envelope (cf., a teabag). If unitized as such, the fibrillated fiber units can be employed as a single layer or as multiple layers.
The deep gradient-density filter device, in view of the flexibility and modifiability of its specific construction can be employed in various fluid processing applications. Of these, one particularly novel use is in the post-fermentation or post-culture biopharmaceutical fluid clarification.
The deep gradient-density filter device 100 can be employed in a broad variety of filtration applications. Types of industrial applications include, for example, pharmaceutical manufacture, processing blood plasma or serum fractionation products, ophthalmic solution manufacture, the manufacture of specialty chemicals, and the like. Despite such applications, the type of activity for which the deep gradient-density filter device 10 is particularly well targeted is in the primary or secondary clarification of raw cellular culture suspensions.
Aligned with unique features of its product embodiments, the present invention provides a method for effectively and efficiently clarifying a manufactured protein-containing biopharmaceutical fluid, in particular a protein-rich cultured or fermented cellular broth. Although methods of clarification are known, the inventive method is characterized by its unprecedented operating regime, i.e., operation at pressures and fluid velocities not before employed with fluid of such high solids concentration and small particle size range (cf., substantially less than one micron).
The ultimate goal of the methodology is to separate the protein-rich fluid from the cellular culture broth debris, which typically contain cells, organelles, and fragments thereof, as well as other particulate and/or solid matter. In so-called pilot scale manufacture (e.g., batches of generally under a thousand liters), the deep gradient-density filter device 10 can be employed immediately after the fermentation or culture of the biopharmaceutical fluid (i.e., so-called "primary clarification"). In so-called industrial scale manufacture (e.g., batches generally in the order of several thousands of liters), the great amount of debris found in such fluids will generally be first removed by other primary clarifications methods such as, for example, centrifugation. The pre-clarified broth can then be subsequently clarified (e.g., so-called "secondary clarification") by the deep gradient-density filter device 10 without substantial incidence of premature plugging.
In the typical bio-industrial procedures, the intent is to remove all of the cellular debris from the fluid, passing all protein. Applicant however believes that the extent of removal is discretional and will depend on a user's needs. Accordingly, the invention should not be limited to any quantified criterion for retention and removal, but rather, the inventive methodology is performed essentially with "substantial" isolation.
As stated, the manufactured protein-containing solution is conducted through said deep gradient-density filtration device under conditions sufficient to effect passage of said protein through each of its zones. By this step, any solid macroscopic debris of the cellular host colony or broth is separated from the protein-containing solution, said debris being substantially prevented from passage through device 10's matrix of filtration media.
The protein-containing solution treated under the inventive method are those typically extracted from industrially-manufactured cell cultures for the purpose of accessing, for example, the biopharmaceutical activity of said protein. Many of these proteins are quite complex in their structure, and are increasingly used in research, diagnostics, and therapeutics.
The exact constituency of the protein-containing solution does not limit the scope of the inventive methodology. However, the present invention does not seek to capture all types of protein-containing fluids. Rather, the inventive methodology is drawn to a "manufactured" protein-containing solution. It is "manufactured" in the sense that the protein contained in said solution is present in a form and/or concentration that does not naturally exist, for example, it occurs in enriched concentration (i.e., a concentration that does not occur naturally or spontaneously without human intervention) or otherwise has detectable genetically-engineered features. Such scope is best understood in consideration of the basic elements of biopharmaceutical manufacture.
While the field is still comparatively new, and thus subject to change, two processes for producing therapeutically-active or otherwise biologically-significant proteins are commonly-employed—though others exist—in the biopharmaceutical arena: i.e., the secretion of monoclonal antibodies from cloned hybridoma cell lines, and the synthesis of proteins using recombinant DNA technologies.
Monoclonal antibodies are produced by fusing single antibody-forming cells to tumor cells grown in culture. The resulting cell is called a hybridoma. Each hybridoma produces relatively large quantities of identical antibody molecules. By allowing the hybridoma to multiply in culture, it is possible to produce a population of cells, each of which produces identical antibody molecules. These antibodies are called "monoclonal antibodies" because they are produced by the identical offspring of a single, cloned antibody producing cell. With the advent of hybridoma technology and other progress in genetic engineering of eucaryotic cells, mammalian or yeast cell lines are becoming the method of choice for producing complex proteins on a large scale.
Recombinant DNA technology involves the integration of a specific DNA fragment into a rapidly replicating genetic element (e.g., a plasmid) so that it can be amplified in bacteria or yeast cells. These cells multiply in culture, each containing the protein-coding plasmid. Translation of the DNA fragment on the plasmid yields the protein-encoded therein.
The deep gradient-density filter device is used for filtration of manufactured protein-containing solutions resultant of either the monoclonal antibody or recombinant DNA technologies. Because of the design of the novel deep gradient-density filter device 100, the method is capable of being operated for longer periods of time before it becomes necessary to replace modules, the filtration material thereof being spent, essentially becoming far too plugged with particles to be used further. As practitioners in the art will appreciate, there is great value to be realized in reducing replacement cycles, as every replacement will typically require "shut down", for maintenance, cleaning, and testing, before recommencing operation. One should reduce the frequency of such down-time, otherwise productivity suffers, which ultimately raises the cost to the consumer of the pharmaceutical product and/or reduce its supply.
While only a few illustrative embodiments of the present invention have been discussed, it is understood that various modification will be apparent to those skilled in the art in view of the description herein. All such modifications are within the spirit and scope of the invention as encompassed by the following claims.
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|Flexible filter element employing filtering sheets formed with bypass openings
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|Filtration arrangement
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|Cuno Incorporated
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|Fibrous absorbent material and methods of making the same
|Título no disponible
|PCT International Search Report, Int. App. No. PCT/US03/38630, Forms PCT/ISA/210 and 220 (Date of Mailing: Oct. 11, 2004).
|Patente citante
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|27 Jul 2006
|18 Dic 2007
|The Clorox Company
|Water contaminant indicators
|3 Abr 2008
|19 Abr 2011
|Cummins Filtration Ip, Inc.
|Static dissipative filtration media
|9 Mar 2011
|20 Dic 2011
|Kuss Filtration Inc.
|Static dissipative filtration media
|3 Feb 2006
|5 Jun 2012
|Eppendorf Ag
|Filter pipette tip
|6 Abr 2009
|9 Oct 2012
|E I Du Pont De Nemours And Company
|Air filtration medium with improved dust loading capacity and improved resistance to high humidity environment
|18 May 2010
|18 Jun 2013
|Johns Manville
|Filter medium
|14 Dic 2012
|12 Nov 2013
|Scientific Plastic Products, Inc.
|Cap with filter and transfer apparatus
|15 May 2013
|12 May 2015
|Johns Manville
|Filter medium
|29 Feb 2012
|22 Sep 2015
|Eppendorf Ag
|Filter pipette tip
|12 Nov 2012
|19 Abr 2016
|Whirlpool Corporation
|Customizable multi-stage water treatment assembly
|12 Nov 2012
|26 Abr 2016
|Whirlpool Corporation
|Filter housing for small media
|12 Nov 2012
|3 May 2016
|Whirlpool Corporation
|Customizable multi-stage water treatment system
|15 Oct 2013
|3 May 2016
|Scientific Plastic Products, Inc.
|Cap filtration tool and transfer system
|21 Oct 2014
|4 Abr 2017
|E I Du Pont De Nemours And Company
|Electret nanofibrous web as air filtration media
|31 Mar 2011
|18 Jul 2017
|Lazer Sport Nv
|Helmet cover
|3 Feb 2006
|10 Ago 2006
|Christian Ziegmann
|Filter pipette tip
|27 Jul 2006
|23 Nov 2006
|The Clorox Company
|Water Contaminant Indicators
|2 Abr 2007
|23 Jul 2009
|Tokyo Electron Limited
|Gas purifying apparatus and semiconductor manufacturing apparatus
|3 Abr 2008
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|Cummins Filtration Ip, Inc.
|Static dissipative filtration media
|18 May 2010
|9 Dic 2010
|Christian Hassman
|Filter medium
|9 Mar 2011
|30 Jun 2011
|Cummins Filtration Ip, Inc.
|Static dissipative filtration media
|31 Mar 2011
|15 Ago 2013
|Lazer Sport Nv
|Helmet cover
|13 Dic 2013
|12 May 2017
|Scientific Plastic Products, Inc.
|Kappenfiltrationswerkzeug und Transfersystem
|13 Dic 2013
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|Scientific Plastic Products, Inc.
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|21 Oct 2014
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|Electret nanofibrous web as air filtration media
|Clasificación de EE.UU.
|55/486, 210/493.1, 210/787, 95/287, 210/348, 55/487, 210/338, 55/320, 55/498, 210/497.1
|Clasificación internacional
|Clasificación cooperativa
|Clasificación europea
|26 Abr 2010
|Fee payment
Year of fee payment: 4
|31 Ene 2012
Owner name: EMD MILLIPORE CORPORATION, MASSACHUSETTS
Effective date: 20120101
Free format text: CHANGE OF NAME;ASSIGNOR:MILLIPORE CORPORATION;REEL/FRAME:027620/0891
|26 Mar 2014
|Fee payment
Year of fee payment: 8


text:
Website www.madinatjumeirah.com/dar_al_masyaf
An excellent choice! The Dar al Masyaf is the more private enclave within the Al Qasr, so if you are asking for transportation from the Dubai Airport, tell them to take you to the Al Qasr lobby, where you will take an abra (boat) or buggy (golf cart) to your building. There is a small pool for every three or four buildings (each with about 8 rooms; 4 upper with balconies and 4 lower with patios). There is a butler for each building, which is essentially a concierge service. The butler also holds a nightly happy hour (6:00 to 8:00 pm), which is a nice touch so that you can enjoy some complimentary drinks and snacks and swap stories with other travellers. The rooms at the "Dar" are lovely, with a king-size bed, large seating area (two couches and coffee table), wet bar, dressing room area, and huge bathroom (separate shower, bathtub, water closet with toilet and bidet, twin sink vanity). GREAT selection of toiletries: separate shampoo, conditioner, body wash for men and women, toothbrushes, paste, talcum powder, lotion, cotton swabs, nail kit, sewing kit, shower cap). They supply nearly everything that you will need (minus mouthwash, floss, razors). You are supplied with robes (two kinds per person) and slippers, and more towels than you can use (they do the towel animals, too). Rooms have hair dryers and safes. You also get a fruit basket (replenished daily), and two boxes of amazing sweets (in neat leather boxes that you can keep). Bottled water is free in the rooms. The lighting in the rooms is good, with plenty of artificial and natural light. The mini bar prices are steep ($5 for a can of soda), but comparable to the hotel itself. We ate a light breakfast in the Al Faroozh lounge, where four sodas and two bagels with cream cheese ran about $15 (not bad). There are also two breakfast buffets, but it was too much food for us. There were too many restaurants on the property to mention; sadly, we did not use any of them for dinner. We didn't eat on our first night after arriving late, and we chose to eat at the Mall of the Emirates on our only other night there. We walked along the concrete pathway past the ocean and the main Al Qasr pool (huge, great amenities like fruit kabobs, Evian facial sprays, cold towels throughout the day), and staffed by TONS of lifeguards. (In fact, EVERY pool had its own lifeguard, even the small ones). We didn't really see the Mina a'Salaam, and unfortunately, it was TOO ungodly hot in August to take advantage of our free visit to the Burj al Arab (which was not as tall as I had imagined). August really isn't the best time to visit Dubai. While 107 degrees merely sounds hot, with the humidity, you really can't be outside for even 2 minutes without sweating and experiencing breathing difficulty. I'm not sorry that we stopped over in Dubai; it's something to be seen once, but I wouldn't hurry back for an extended stay anytime soon.
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Dubai: Dar al Masyaf Review
Website www.madinatjumeirah.com/dar_al_masyaf
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The Burj al Arab is taller than it appears.
This from Hillmans Wonders: The hotel is significantly taller than it appears to the eye. The Burj Al Arab's streamlined shape and its double floor design help create the optical illusion. To grasp the Burj Al Arab's height, imagine the 102 floor Empire State Building standing next to the the Burj Al Arab, which is just 16% shorter.
You can appreciate its height from the Skybar.
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I wish it wouldn't have been so ungodly hot that we could have walked over and checked out the Burj. We even had free access to look around as guests at the Dar, but the heat was truly unbearable. I'll take your word--and Hillmans--that it is taller than it looks. It certainly is unique.
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fluffnfold: Was this hotel part of the Emerites overnight offered with their business class ticket purchase? We are considering going for the AmX platinum in order to obtain the tickets 2 for 1. Is that what you did and was it worth it to you. Did they give you choices in Dubai as to where you would stay? I know its unbearably hot there but yet feel if I fly in I should see it! Thx Cc
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I tried to get the free overnight package, but Emirates told me that since we bought the tickets through the Amex International Airfare program (buy 1/get 1), that they weren't really full-fare tickets, so we didn't qualify. (Only one of us got frequent flyer miles, too, but I guess we should have expected that. They were on United, though, so very usable.) With the free nights, though, if you purchase a first class ticket, you can stay at the Ritz Carlton, I think (since it didn't apply to me, I'm not positive). With the business class tickets, you had to stay at the Jumeirah Emirates Towers, which seemed quite nice, although located in the business area as opposed to near the beach, where I really wanted to be. For free, I would gladly have taken it and driven over to see the ocean. You also got some hotel credit for meals, spa services, with the promotion--I think it was $100 per stay or $100 per night. In any case, with Amex we didn't qualify.
We bought business class tickets, but it wasn't exactly the buy 1/get 1 deal that I had priced myself. You must buy the higher priced refundable no-restrictions business class ticket, of course, not the least expensive one that you are probably seeing online when you look yourself. For example, business class seats were priced around $7000 each when we booked (I think the price is still similar), but we had to buy the first ticket for $10000 in order to qualify for the promotion, then just pay the taxes on the second ticket (around $150, I think). I really didn't intend to give prices, but I wanted you to know--I wish I had known ahead of time that it isn't exactly as it sounds. To defend myself, this was the trip of a lifetime (and my dream vacation), so it was a real splurge for us. And it was actually worth it! The flights (well, JFK to Dubai anyway) were fantastic--great seats, entertainment, service, food, and we slept for the first time on any international flight (worth its weigh in gold, arrived with no jetlag, not really needing the 2 nights in Dubai to recuperate). The tickets are also fully-refundable, so we figured that we saved on travel insurance (which would have been 2% to 4% of the total cost of the tickets). I also (foolishly) thought that if the fares dropped, we could cancel and rebook at the lower fare with no questions asked (and we could have, except that the fares never dropped during the entire 11 months that I looked).
Would I purchase with their program agin? Probably, provided I had the funds it was still cheaper than buying two separate business class tickets). It's really easy to get used to sitting in the front! Would I stop over in Dubai again? Probably not, but like you, I just had to see it for myself rather than taking someone else's word. Maybe you can stay for just one night? If you time your arrival and departure right, it might leave you with enough time to see something. I wish that we had spent that second night somewhere on safari because it's so much more special. Dubai is newly-built, manufactured, and HOT HOT HOT (and therefore not especially enjoyable to me)! Glad that I saw it, but probably wouldn't spend the time again.
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Thanks so much for the info. We are trying to decide whether or not to splurge for the business class - mainly because of the comfort factor in that I have major hip problems and would rather be "up front" than squeezed in the rear of the bus. And, we would like to break the trip up ,but instead of flying through Europe these days, I'd rather go to Dubai. My neighbor's daughter teaches there and is looking for a place for us to stay, so if she can find something reasonable (unfortunately she will be moving on by the time we travel in '08)we will stay one night. I appreciate your forthright answers: its difficult telling the world about your finances, but for most of us this is a dream trip coming true, and we should just go for it! Everyone says we will be hooked and repeat our travels to Africa; and I would love for that to be true, but I honestly do not think it will be a monetary possibility to do so in our case. So I am planning to make the most out of this one opportunity...We are also staying in higher end lodges and flying to them instead of driving. Just a choice one needs to make for their own desires! I am also looking forward to a soak in a tub after bumping around in a rover all day!
Thanks for all your reviews of your trip and your response to my questions. We will be going to Kenya in Sept. 2008 and I hope I can return the favor to someone when I return! CC
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subset: commoncrawl


text:
DRI*Trend Micro
Complaint 59115 Details
- Date Occurred: 07/18/2013
- Reported Damages: $62.95
The complaint is against an online dating profile
The complaint is a listing fraud posted on public forums or sites against an anonymous entity
The complaint is mobile text spam or smishing related against an anonymous entity
The company or person contact no longer exists
International boundaries
This charge was made to my credit card without authorization.
It can not be have two different DRI Trend Micro at the same year.
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text:
Blood-soaked Valentine(Reverse Valentine's Day Challenge for Chloe the guitar girl)
Reads: 830 | Likes: 0 | Shelves: 0 | Comments: 16
Poem by: mommy3
Blood-soaked Valentine
I thought he loved me.
I guess I didn't see.
He came over to kiss me.
I kissed him back thinking it was meant to be.
He took out a knife
I ran for my life
He screamed a high yell
That is when I fell
He grabbed my leg
I continued to beg
I screamed I love you.
He yelled I never loved you.
He stabbed me in the heart
I guess my life was meant to part.
He grabbed me by the neck
To give me one last peck
I guess he never loved me.
Everyone else knew and it was plain to see.
I guess I was in denial
That boy my boyfriend was vile.
I thought what a great Happy Valentine's Day.
I would find a way to make him pay.
Even if that meant I would come back from my grave.
I would make sure he wasn't so brave.
I would him haunt to the end of my days.
I would make sure his life would end in so many ways.
I will kill him in a most painful death.
I would make sure he had no more breath.
© Copyright 2017 mommy3. All rights reserved.
Add Your Comments:
This was an interesting and slightly contrived poem in as much as the verses seemed a little forced to rhyme.
Lovely picture glad i've had my dinner,i laughed at the comment where he stabbed you in the heart and you still had enough breath to say "i love you" i don't think so you would be lying dead instantly.
Still this was a good read and enjoyable enough to comment upon.
I love this poem. It was really good valentine poem. What made you think of doing that?
Yes this rhymes magnicently and is much improved thank you for not being offended by my remarks i just think you are such a talented lady that it seems a shame that you have all the ingredients within a great poem and much like a jigsaw poem you have put them all in the right mix to create a perfect poem.
hehe It was still a little early for me. I had a rough night with my little girl. I think she is starting to get sick. Didn't get that much sleep and kind of rushed this poem together. I appreciate your advice so it helped me change it around. thank you Jessica :)
Wow, freaky shizzle that.
I loved the idea of an anti-valentines day story, and I think you ebraced it really well. I enjoyed it, especially her vows for revenge. :D
Zoe. x
Freaky my friend. You really know how to spook a girl. Imagine that. Think I'll keep valentines day on the lovey dovey side. Lol! Great Job! Good Luck!
Really scarey and spooky write. I felt my heart go Boom Boom Boom on this one. I think you did great considering what you had to do. Good luck my friend. Hope you win. Got my vote. Susan :)
Well done. Excellent entry. Giving my vote as well. Hope you get first!
I feel this poem. It was great. You did an awesome job. Thumbs up!
Excellent entry! Good luck. Giving you my vote. M
well done, well done, I really like it :)
So macabre, I think her coming back from the grave would make a good short story, rather like those Japanese films, ring grudge and shutter. Good write Jessica.
Dark and definatly opposite to valentines day. Well written
It sounds like revenge is in the air rather then love. Haha. A good scary poem.
It was kinda sad, but somehow it made me smile. I dunno, perhaps I'm crazy, but this was a jod well done! I really like your poems!
This is a great poem, much improved and you do these poems very well, the dark side of love.
That was amazing :) I cant wait to read your challenge submission! good work! :D~Fauxe
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text:
Thanks to our hard-working intern Emily Hutton, we have recently posted eight great articles about birds and birding from past issues of the magazine. Each one is a treat; they include profiles of Great Horned Owl and Roseate Spoonbill, a beautiful essay about two Massachusetts birding legends, and a newspaper reporter's commentary on his love of birding (above). The stories are listed below, and you can find them cross-posted in the Backyard, Birds, Birding, or Conservation sections of this site. Enjoy!
A time to kill?
How the Barred Owl's success in the Pacific Northwest is forcing managers to think the unthinkable. Charles Bergman, October 2012.
Why sapsuckers often choose to make their nests in living, not dead, trees — and aspens in particular. Warren Uxley, October 2012.
Great silent hunter
Why late fall and early winter are the best times to listen for the Great Horned Owl. James D. Ray, December 2012.
In search of pink gold
Why the fate of the Everglades is tied to the fortunes of its most stunning bird, the Roseate Spoonbill. Mac Stone, February 2013.
Whip-poor-will synchronicity
Two local birding legends were always first to hear the hopeful song that inspired Faulkner. John R. Nelson, June 2013.
Most wanted
Our readers want to see these 10 species more than any others. Matt Mendenhall, August 2013.
My once-in-a-lifetime hummingbird
Neither Hurricane Sandy nor winter snow could budge this feisty Rufous Hummingbird from its perch in eastern Pennsylvania. Suzanne Kimball, October 2013.
Why I love birdwatching
How a pair of better binoculars, Aldo Leopold, and the death of my parents combined to make me a birdwatcher. Frank Zufall, October 2013.


text: The World Resources Institute has written an informative article about tips on how to remain in compliance of the Lacey Act. The article discusses the Gibson Guitar raid, as well as other cases relating to the Lacey Act, and what you can do to make sure you are operating within the law. We urge you to read it, in order to stay informed on these issues.


text:
Mineral City Private Schools - starts with R
The 50States Mineral City private school directory. Find Mineral City, Ohio private school addresses, phone numbers and other private school info.
Go To: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
No Listings


text:
Census road tour begins next week
The Census Bureau's road tour to promote the 2010 Census will begin next week.
The road tour will kickoff on Jan. 4 in Times Square in New York City.
Thirteen tour vehicles will travel more than 150,000 miles across the country to educate people about the 2010 Census. The tour will stop at more than 800 events, including parades, festivals and the Super Bowl, according to the Census Bureau.
Tags: 2010 Census, event, New York City, road tour, times square


text:
The win keeps the Vikings on pace for the playoffs, and continues a dramatic reversal after the team struggled through the first half of the season.
Lots of pro football games are played on Sunday, but only one on Monday. That contest tends to get more than its share of attention from the nation's sports writers and broadcasters.
This week the common story line was, "What's up with those purple guys in Minnesota? How can a team lose five of its first seven games, then turn around and win six of its next seven?"
When a version of that question was posed to the architecht of this winning streak, Vikings head coach Brad Childress peered through his spectacles and explained the turnaround in unglamorous, workmanlike terms, perhaps fitting for flyover land.
"Just brick by brick. I mean, we've been really play by play and gone practice to practice," said Childress. "We're not good enough to look out over the horizon, we've really got to take them one game at a time. I know that's trite, but that's how we've looked at it."
Minnesota players also provide no dramatic tales of turning points. Linebacker Chad Greenway says even after the Vikings were demolished 34-0 by the Green Bay Packers, coach Childress shunned any changes and kept the team focused on the immediate task at hand.
"We stayed the course. We don't think too far ahead, we take it one game at a tiime," said Greenway. "The biggest thing that I think has changed is our preparation. We're a little more focused during the week, and we know what we need to do to win a football game. But it doesn't get any easier next week."
The Vikings are a young team. Greenway, for example, is in only his second pro season and missed his first year due to an injury. Quarterback Tarvaris Jackson is also a second-year pro who played sparingly as a rookie.
Inexperience sometimes breeds mistakes, but the Vikings are working on learning from those. Jackson had plenty of learning opportunities against the Bears, as he fumbled the ball away once and threw three interceptions.
But Jackson said he employed the team philosophy of focusing on small increments, and not getting discouraged.
"You can't dwell on it. The most important play is the next play. I turned the football over. I understand what I did wrong, what happened. And so, just move on," Jackson said. "We still had a game to play, and we rallied and we won the football game. That's a part of my job, to move on. As a quarterback you've got to have a short memory."
Tripped up by their turnovers, the Vikings fell 10 points behind Chicago, then recovered slightly with a field goal just before halftime.
Safety Darren Sharper, one of the veterans on the team, says there was a time when the Vikings might have been rattled by the sort of struggles they encountered in the first half against the Bears. But Sharper says now the team can take a seven-point halftime deficit in stride.
"The coach said not to panic, just come out to play. The offense had the ball first. So the attitude was we were going to go and score on the first drive. But we weren't panicking at all because there was lot of football left to be played," said Sharper.
The Vikings defense held Chicago scoreless after halftime, with Sharper's interception squelching the Bears' last chance.
On offense, Minnesota's running game finally got untracked in the second half, with rookie Adrian Peterson scoring both of the Vikings' touchdowns.
Peterson's running -- specifically his knack for breaking loose for long runs -- has been a key element in Minnesota's offense this year. The Vikings have tied a team record for most times gaining 50 yards or more on a play, accomplishing that 19 times.
There's no doubt that Peterson's speed helps account for that statistic. But he says the abundance of big plays starts with good blocking, especially by the starting linemen, Bryant McKinnie, Steve Hutchinson, Matt Birk, Anthony Herrera, and Ryan Cook.
"It starts up front with the offensive line - Matt Birk, Hutch, Big Mac -- and those receivers outside, they're doing a great job downfield," said Peterson. "So those are really all the ingredients that have contributed to the big runs we've had this year."
Peterson has shared the running duties with Chester Taylor, and says splitting the workload has helped each stay fresh. Tackle McKinnie says slight differences in the running styles of Peterson and Taylor also help keep opposing defenses from getting too comfortable.
The Vikings will play their last home game of the season against the Washington Redskins on Sunday night in another nationally televised game.
If their closest competitors for the final playoff spot -- the New Orleans Saints -- lose their game Sunday, then Minnesota could lock up a post-season berth with a victory.


text:
Lindsey Bareham's 50 favourite midweek meals
She's renowned for her masterclasses. Here the Times cookery writer reveals her kitchen secrets and best-loved recipes
Using Google Chrome or Firefox as your browser, click on the "Recipes" tab above to view new recipes each day this week.
If it's Monday, it must be shepherd's pie (if Sunday's roast was lamb). On Tuesday and Thursday it might be stew or meat and two veg, then bangers and mash or macaroni cheese on Wednesday, and fish, always fish, on Friday. That is how I was brought up. There was always a hot home-made pudding and we had to eat everything on the plate. Even as a child I was an embryo foodie, fussy about a particular fork or how the food was placed on the plate, but left home rake-thin with no discernable cooking skills.
I didn't start cooking seriously until a…


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GCEF Awards First Round of Small Grants
Attorney General Schneiderman, Department of Environmental Conservation Commissioner Martens and Senator Dilan announced the first series of grants to be awarded through the Greenpoint Community Environmental Fund (GCEF).
The state is awarding $395,135 in small grants – between $5,000 and $25,000 – to 18 environmental improvement priority projects identified by Greenpoint residents. The proposals are the culmination of nearly two years of public meetings that helped shape many of the projects receiving grants. Together with an additional $196,916 in matching funds, a total of $592,055 will go toward Greenpoint's environmental priorities.
"After suffering more than a century of industrial negligence, Greenpoint is finally getting the attention it deserves. These initial grants mark the culmination of decades of community advocacy and the diligence of state environmental officials and the state Attorney General's Office. I commend Attorney General Schneiderman, Department of Environmental Conservation Commissioner Martens, all those that submitted proposals, and especially the members of the Greenpoint Community Advisory Panel for their dedication and hard work. Each of your efforts will leave a lasting impact on the Greenpoint community that will inspire future generations of Greenpointers," said Senator Dilan in the naming of the recipients.
GCEF is expected to award additional projects through two more grants, a legacy and large grant, this October.
The GCEF is a $19.5 million grant program created by the State of New York with monies obtained through a settlement with ExxonMobil over its Greenpoint oil spill. The GCEF's goal is to fund projects that will address the Greenpoint community's environmental priorities through a process that is open, transparent, and ensures ongoing engagement and partnership with the community.


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Disconnection and Termination of Service
Disconnection and Termination of Service
A. Termination Initiated by Company
The disconnection of a Customer and provisions for restoration of service shall be governed by MPUC Rules and Regulations, Chapters 810 and 860. The Company will charge a reconnection fee of $25.00 during normal business hours. For reconnection after normal business hours, the Company will charge a reconnection fee of $80.00. For purposes of this section, normal Company business hours shall be from 8:00 a.m. until 4:00 p.m. Monday through Friday excluding Holidays and the charge shall be determined as of the time the Company receives the request from the customer.
B. Termination Initiated by Customer
If the Customer wishes the gas service to be terminated he shall give notice at the office of the Company at least five (5) days prior to the time that such termination shall become effective, subject to any existing agreement between Customer and Company. The Customer will be held liable both for any gas that may pass through the meter and safe custody of the Company's property until five (5) days after such notice shall have been given, provided that the meter and/or other movable equipment shall not have been removed within that time by the Company.
Notice to discontinue service prior to the expiration of a contract term will not relieve a Customer from any minimum, or guarantee payment under any contract or rate.
If, by reason of any act, neglect, or default of a Customer, the Company's service is suspended, or the Company is prevented from supplying service in accordance with the terms of any special contract it may have entered into with the Customer, the monthly minimum charge for the unexpired portion of the contract term shall become due and payable immediately as liquidated damages in lieu of the anticipated returns from said contract.


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Posted on December 13, 2011
Event Date:
Thursday, December 22, 2011 - 9:30pm
Tune in for Mack's Rock & Roll Christmas Spectacular Extravaganza on Thursday, December 22 from 9:30 pm to midnight.
DJ Mack brings you an evening of rockin' reindeer, surfin' Santas and rockabilly snowmen. Have a cool yule, a crazy Xmas & a swingin' holiday with Mack.


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- Share
Bermuda Triangle II
Dr Karl had assured us that The Bermuda Triangle is no more perilous than any other stretch of water. But there are still some spooky things going on beneath the waves...
Last time I talked about the myth of the Bermuda Triangle, that triangle of ocean between Bermuda, Puerto Rico and Miami, where ships supposedly vanish for no good reason. But when you look at the statistics, the sinkings are on a par with any other similarly-trafficked area of ocean real estate anywhere else on the planet. The extra sinkings are not real. But there is something very strange lurking under the floor of the Bermuda Triangle - an ice that burns.
In fact, this bizarre ice exists in many other places around the world as well. It's called a "methane hydrate". Basically, it's a single molecule of methane trapped in a cage of six water molecules. Methane has the chemical formula of CH4, which means one atom of carbon is surrounded by four atoms of hydrogen, while water is your standard H2O. If you have methane and water together in the same place, and if the pressure is high enough and the temperature is low enough, you can get a methane hydrate. If you bring a lump of methane hydrate to the surface, the icy water melts releasing the methane, which will burn quite nicely. In one sense, these methane hydrates are kind of like vampires - they will fall to pieces if you bring them out into the light.
These hydrates have been a scientific curiosity for about two centuries. It was only in the late 1960s that Russian scientists discovered natural hydrates in the freezing Siberian permafrost. In the 1970s methane hydrates were discovered at the bottom of The Black Sea. The Black Sea is loaded with these methane hydrates. In fact, sailors have long reported seeing bolts of lightning set fire to the methane on the surface of the sea - methane that had spontaneously bubbled up from below the ocean floor. And since then, they've been found in many many places under the ocean floor, including the notorious Bermuda Triangle.
In fact, there's a huge amount of methane down there. For example, about 330 kilometres off the coast of North Carolina, and three kilometers below the surface of the ocean, is a uprising on the ocean floor called Blake Ridge. This Blake Ridge covers around 100,000 square kilometres of the ocean floor. One quarter of it, just 25,000 square kilometers, holds methane equivalent to around 35 billion tonnes of carbon. In plain English, that deposit of methane would be enough to cover the entire natural gas consumption of the USA for a hundred years. And yet this is just one small area of methane hydrates.
Where did all this methane come from? The answer starts with all the dead bodies of various sea creatures floating down to form a mud on the ocean floor. Strange creatures like bacteria called Archaea, live down there, and eat these dead bodies. If you think that ice-that-burns is weird, these Archaea are even weirder.
Back in the old days, about a quarter-of-a-century ago, the biologists divided life into Five Kingdoms - plants, animals, fungi, protists (single-celled creatures with separate nuclei) and bacteria (single-celled creatures without separate nuclei). But in the late 1970s, Dr. Carl Woese and his colleagues from the University of Illinois started looking at these creatures from the point-of-view of their DNA. They found that some bacteria didn't really belong neatly with the other bacteria. They were small, like regular bacteria, but they had major differences in the DNA, in their cell membranes, and in a whole lot of other areas. These weird bacteria-like creatures often lived in extreme conditions where bacteria could not - temperatures over 100oC, extreme pressure or extreme saltiness. They called these weird bacteria, Archaebacteria, which they later shortened to Archaea. After a while, these scientists realized that all living creatures could be separated into three Domains - the bacteria, the Archaea, and everything else.
It seems that some of these Archaea have been around since the very first days of life on our planet, about 3.8 billion years ago, long before there was any oxygen in the atmosphere.
Some of these Archaea make methane, while others eat it, and sometimes, there's enough methane left over to form these methane hydrates. If these little methane eaters didn't exist, there'd be an extra 300 million tonnes of methane each year bubbling up from the ocean floor. Methane is a very powerful greenhouse gas, about 20 times more powerful than carbon dioxide, and that would set off some pretty significant warming on our little planet. So we're lucky that these methane producers live next to methane eaters.
There seems to be a lot of them around. Some scientists have calculated that the primitive Archaea and other bacteria-like creatures living on the ocean floor make up one third of all the biomass of living creatures on our planet. So in about quarter-of-a-century, these Archaea have gone from completely unknown, to making up one third of the biomass on the planet!
Now sure, a bit of methane bubbling up to the surface can burn in a pretty way if it's hit by lightning - but it can be a lot more dangerous than that, and I'll talk about that, next time...
Published 01 November 2005
© 2017 Karl S. Kruszelnicki Pty Ltd


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Lufthansa resumed flights to Beirut
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As of 9th September flights resumed after airport closure
After the re-opening of Rafik Hariri International airport, German Airline Lufthansa re-establishes its flight operation to the Lebanese capital. As of Saturday, 9th September, customers have choice of five flights a week from Frankfurt to Beirut.
About Lufthansa German Airlines
Lufthansa is one of the world's biggest and most prestigious airlines. Also, renowned as the World's favorite International Airline, Lufthansa successfully owns a fleet of 390 aircrafts and is among the world's top ten airlines. Lufthansa proudly is also a founding member of the Star Alliance which offers more than 15,500 daily flights to over 842 destinations in 152 countries.


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Sedona Fire District Assistant Fire Chief Terry Keller will bid farewell to the SFD this month as he prepares for his new role of fire chief for the Montezuma-Rimrock Fire District.
Keller, who served as interim fire chief in Sedona until the hiring of SFD Fire Chief Kris Kazian, will begin his duties with the MRFD Monday, Feb. 4. Keller will replace retiring fire chief Mike Van Dyke.
Keller's new position was announced in the first week of July. He applied for the position last March. Keller worked in Sedona for the last 24 years. He's served as assistant fire chief since 2007. Prior to that, he worked as an SFD battalion chief. Keller began his career as a volunteer for the district and worked his way to assistant chief of operations.
For the full story, see the Wednesday, Jan. 23, edition of The Camp Verde Journal.


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If you heard about the Family Survival Course by Jason Richards and you wonder if this survival course is really for you, then you came to the right place.
In this Family Survival Course review you will discover what the Family Survival Course is all about, exactly what it contains, what are the good and bad points of this popular course and much more important, you'll learn if Jason Richards' course is really the right one for YOU or not.
Bear in mind that this is only a review about the Family Survival Course, if you are looking for the Family Survival Course official site or if you want to enjoy limited time SPECIAL discount for Jason Richards' complete course then click here now.
OK, Let's start by understanding better what the Family Survival Course is all about…
What Is The Family Survival Course?
A Short description
Created by Jason Richards, an avid outdoors man and ex military with extensive experience in private security, the Family Survival Course is a complete set of eBooks that supposed to teach you how to protect your family during the upcoming political and economic crisis, which many people believe will happen at the US in the near future.
The Family Survival Course can be divided into three main parts:
The first part talks in great details about the current situation at the US and give you many explanations about the real danger of a disaster in the near future. The second part discusses about the preparedness level of most people and households in the US, while the last part, which is the main part of the course, shows you exactly what you need to do in order to ensure the safety or your family not just in the short term but also in the long term.
What Is Included Inside The Family Survival Course :
Like we mentioned before, Jason Richards divided his Family Survival Course into several guides and in short here are the main eBooks and components that you will find inside his survival course:
- The Family Survival Beginner Course
- The Family Survival Advanced Course
- The "Home Made Food And Natural Remedies" Guide
- The "Medical Emergency Survival" Guide
- The "No Stress During The Crisis" Report
- The "Seasonal Survival" Guide
- The Short Guide On How To Survive Any Disaster
- The Quick Start Guide that explains what you will find inside the course
The Pros And Cons Of The Family Survival Course
The Pros
- The course contains information for both beginners and advanced users, something which makes it much more effective and organized.
- This Course covers lots of topics and it is one of the most comprehensive family survival courses you will find online.
- All the material inside the Family Survival Course is available for an instant download.
- The main guides of the Family Survival Course talks about the short term, the midterm and the long term separately, something which we really liked.
- Almost all of the things that Jason Richards recommends to buy in his course are really cheap and easy to get, and most of the chances that you already have some of them at home. There is no need for any expensive survival gear!
- We really like the way of writing that Jason Richards uses in order to teach you how to recognize the potential in everything you own, something that can save you a lot of time and money.
- The Family Survival Course comes with 60 days money back guarantee so there is no risk at all.
The Cons
- The Family Survival Course requires some minimal lifestyle changes such as the things you buy, how you store your stuff, etc…
- Some level of commitment and cooperation from your family members is required in order to achieve the best results from Jason Richards' survival course.
- We really like that the Family Survival Course contains lots of information on different topics that are crucial for your family's survival, however we found several sections inside this course that have repetitive information and we believe that Jason Richards could make his course shorter.
- The Family Survival Course is available in digital downloadable format which is a great advantage; however people who prefer hard cover books will be disappointed to learn that they won't find it in this format at stores.
Click Here And Discover Much More About The Pros And Cons Of The Family Survival Course Now!
Should You Grab The Family Survival Course?
The Family Survival Course is for you if:
- You are looking for a survival course that combines information for both beginners and advanced users.
- You are looking for a comprehensive course that covers almost any aspect about family's survival.
- You are looking for a survival course that gives you step-by-step directions on the things that you must do in the short term, the midterm and the long term.
- You are looking for a family survival course that comes with full money back guarantee.
The Family Survival Course is not for you if:
- You don't want to or not planning to do any lifestyle changes after getting the course.
- You are on a very limited budget and you are looking for extremely cheap family survival course.
- You think that only purchasing the Family Survival Course without any other actions on your part will help your family survive the upcoming crisis.
Our Verdict:
We personally believe that the Family Survival Course by Jason Richards is the best family survival system available on the internet today and we rated it as our #1 pick with no hesitation.
This course covers almost any topic about family survival and the fact that it comes with step-by-step directions for both beginners and advanced users is a huge advantage.
Having said that, we also believe that the Family Survival Course may not be for everyone.
People who think that this course is a "quick fix solution" or people that don't plan to do even minimal changes in their lifestyle in order to prepare themselves for the upcoming crisis should not get the Family Survival Course.
On the other hand, serious people who are looking for a complete survival course for their family that provides valuable information on every important aspect regarding the short term, the midterm and the long term, will probably find the Family Survival Course to be one of the best investments they ever had.
Moreover, the full money back guarantee from Jason Richards and the great limited time discounted price that he offers for his Family Survival Course these days make this survival course completely risk free and allows you to try it without having something to lose…
Click Here To Get The Family Survival Course For A Very Special Price And Discover Everything You Need To Know In Order To Be Prepared For The Upcoming Crisis Now!
We hope that our Family Survival Course review was useful for you. Feel free to contact us if you have any more questions regarding it.
Have a great day and all the best!


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Editorial: City council right to penalize liquor store
The lawyer representing Rosemount Liquor had the opinion of an independent arbitrator on his side when he asked the Rosemount City Council to consider a less severe punishment for his client. Rosemount City Council members had common sense on their side when they turned him down.
On April 24 an employee of Rosemount Liquor got caught selling alcohol to an underage individual. It was the store's third violation in the past 36 months, the fourth going back to March of 2005. That is unacceptable. Whether or not there was willful negligence involved, three violations in less than three years is hardly evidence the store is living up to its civic responsibility.
And yet, despite the repeat violations the arbitrator who reviewed the case recommended a punishment that included only a software purchase and stayed 21-day license suspension. As at least one council member pointed out last week, that's less severe than the punishment handed out when the store was caught for its second violation in 2006.
The punishment suggested by the city seems more in line with what is called for here. The store has a choice: either close for six days and install a $1,500 software system that will ensure no transaction goes through without some form of identification being checked or forget the software and close for 10 days.
The days with closed doors will almost certainly hurt business at the store, but if it doesn't hurt it's not much of a punishment.
According to the store's lawyer the owners of Rosemount liquor have already started looking into the software system. We think that's the right move. It's right from a business standpoint because it will reduce the length of the store's license suspension but more important it's right because it is a step toward making sure the store is not cited for further violations.
A big part of owning a liquor store is taking on the responsibility of making sure people who are not supposed to have alcohol do not get it. We think any step that brings a store closer to that goal is a good thing.


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Where Are the Thinking Christians? Or, Why We Look Dumb
Does it strike anybody else as absolutely crazy that the man who continues, against all reason and despite a complete lack of necessity, to defend a historical reading of the creation story (see tweet below…)
Just a few minutes later informed his Twitter followers about this:
Really, Mohler? You deny science on NPR, but we should care about your thoughts on bioethics?
On a related note, I met this week with a new friend, the influential writer Karl Giberson. Giberson has been the executive vice-president of The BioLogos Foundation and is author of several books that prove that the kind of willingful suspension of being-a-reasonable-human-being that Mohler continues to display needn't set the benchmark for Christian consideration of science. And, unlike Mohler, Karl Giberson also happens to be a scientist. Incidentally, Karl has gone head to head (or, at least, blog post to blog post) with Mohler on this very issue.
In the midst of seemingly daily debates amongst the current Republican candidates for their party's nomination, the ugly and unthinking underbelly of conservative Christianity has been on prominent display. We have heard cheers for the death penalty, boo's directed at members of the military who happen to be gay, and a ridiculous number of climate change deniers. Now, more than ever, we need to hear from intelligent, thinking Christians like Karl Giberson. By all means, let the pastors teach and preach, but let's leave the addresses on bioethics and biotechnology to those who actually know a thing or two about such topics.
Update: Karl Giberson on "Why Evangelicals Are Fooled Into Accepting Pseudoscience" at The Huffington Post
0 Responses to Where Are the Thinking Christians? Or, Why We Look Dumb
David P says:
You referenced one Christian PhD is Physics. Another Public radio show this week had two people with PhDs in Chemistry and Biology deabting the origins of life. Thinking people all over, and "we" only look dumb when we ignore these people and focus on people we don't like instead.
Where Are the Thinking Christians? Spare us the theatrics.
Fitz says:
David, thank you for your comment. Can you provide a link to the other public radio show? Thanks!
Matthew says:
Point #1: I totally agree with you. It upsets me greatly that Christians buy into pseudoscience and rage about non-issues like 6-day creationism, obstruct progress on important issues like global warming, and botch our rightful voice by misusing science when it comes to really important issues where we should stand up like abortion and stem cell research. I really do care about helping evangelicals think more soundly about these issues, and I think we should be winsomely engaging with our brothers & sisters on these issues.
Point #2: I feel like the smug, condescending attitude exemplified in this short post (and pretty consistently displayed at Patrol) will only make the debate worse. Setting up the "thinking Christians" vs. the "non-thinking Christians" is a rhetorical flourish that only fans the flame of the culture wars and gets the people in your tribe more fired up. If you really want to create dialogue and help the Christian community find its way, please do not be so mean on the internet. Thanks!
Kathy says:
Question for Matthew – What, specifically, have you found to be a successful avenue for engaging in discussions with people of different views? How do you open up a conversation on issues like the relationship between faith and science, or other "hot-button" topics? I wonder if words can ever bridge the gaps, or if we just have to continue to try to work side by side, offering the cup of cold water, and hoping for a very slow change in attitudes.
Matthew says:
Mostly just long conversations over years and years with the same friends. I try not to badmouth people who disagree with me and we respect each other in a lot of other ways, so we can have civil discussions even about heated issues. I think that words can be part of change, but mostly you're right– it's loving the person genuinely and living a faithful life.
I have also really sought to eschew a bitter or mean tone in my internet discourse if I can. There are some friends that I can joke with and I enjoy that, but mostly I try to post things that I've found compelling and then respond graciously & thoughtfully. I look at the sort of rhetoric that makes me annoyed but makes me think and try to emulate that. I look at the sort of rhetoric that makes me not like the position the author takes because they're being cruel and I try to avoid talking like that.
Daniel J. Fick says:
If Mohler isn't a scientist, then we should equally affirm that Giberson isn't a theologian. Therefore, to be sure, we need to find some healthy medium between the two, rather than simply telling the theologians to stay out of the science community, while not telling the scientists to remain out of the theological community. It's a non sequitur.
nathan says:
we should further clarify that Mohler isn't a theologian either. He's a polemicist who sings in a religious key.
david seidel says:
non sequitur and polemicist….this is why I read the sports page
Joe says:
Where are the thinking Christians? Gee, I dunno, but it is obvious where the jackasses are. I mean, really, disagree if you please, but you can be thinking and agree with Mohler. Or, wait, are you a PhD in biowhatever yourself? Or more likely, I writer willing to engage in dramatic name calling. As for Mohler not being a theologian, who really does qualify for this distinction? You guys being enthralled with the zeitgeist never fails to amaze. Wish we could all be so earnest, intelligent, and … never mind. Talk to you when you are in your Forties.
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Cam'ron & A-Trak – "Humphrey" [LISTEN]
It's Killa season. Following the announcement of their collaborative Federal Reserve EP, Cam'ron and A-Trak deliver a proper first single titled "Humphrey."
The Harlem MC finds his footing on soulful production by A-Trak and Party Supplies. Listeners will hear hints of The Diplomats' classic run in the repetitious loop. And then there's Cam'ron, who laced the track with some witty bars and a bank of sh*t talk.
"My parents got high, no lie. It's not shame/ A product of dust, lust, and cocaine," Killa Cam rhymes.
The Federal Reserve release date has yet to be announced, but it's supposed to arrive this spring. The sole features with be Dipset members Jim Jones and Juelz Santana. Stream Cam'ron and A-Trak's "Humphrey" below and sound off your opinions in the comments.