text:
|Publication number
|Publication type
|Application number
|Publication date
|Jan 10, 2012
|Filing date
|Aug 3, 2007
|Priority date
|Aug 3, 2007
|Fee status
|Also published as
|Publication number
|Steven M. Peckham
|Original Assignee
|Warsaw Orthopedic, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (57), Non-Patent Citations (1), Referenced by (5), Classifications (30), Legal Events (2)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention generally relates to a method of using a matrix as a barrier for unwanted cell attachment and bone formation. More specifically, there is disclosed the use of a growth-inhibiting matrix to prevent migration of osteo-inductive agents or bone tissue from an intervertebral disc space through the outer bands of annulus fibrosis that abuts the spinal tissue and canal and other surrounding areas.
The human spine is a complex arrangement of connective tissue, vertebrae, intervertebral discs, the spinal canal, the spinal cord, nerves, and the like. A plurality of vertebrae are stacked upon one another into four regions, the cervical, thoracic, lumbar, and sacrum regions. Intervertebral discs are located between stacked vertebra and abut the spinal cord, which runs through the spinal canal of the vertebrae.
Healthy intervertebral discs make the spine remarkably strong and flexible, being able to bend with ease when under heavy loads. The intervertebral discs have several functions, one of which is serving as shock absorbers for the spine. Each disc resembles a jelly donut, having a relatively tough outer layer, called the annulus fibrosis, that surrounds a gel-like inner layer, called that nucleus pulposus. The annulus fibrosis is composed of concentric layers of intertwined fibrocartilage forming annular bands, which are arranged to resist forces placed upon the spine. The vertebrae's cartilaginous endplate, also a part of the disc space, separates the nucleus pulposus and annulus fibrosis from the adjacent vertebrae.
The nucleus pulposus is composed of cells from the primitive notochord and contains significant amounts of substances capable of exciting, or increasing the excitability of, sensory nerves. These substances include prostaglandin E, histamine-like substances, potassium ions, lactic acid, and several polypeptide amines.
Although the spine is resilient, trauma or osteo-degenerative diseases can cause injury to vertebrae or intervertebral discs, particularly about the lumbar region of the spine. This is a source of chronic lower back pain for millions of people. Tears to the intervertebral discs can lead to herniated disc disease, where the nucleus pulposus migrates into the outer areas of the intervertebral disc space and presses against the spinal cord or possibly collapses vertebral bodies onto one another. Herniated discs or tears in the annulus fibrosis can make the slightest movements very painful.
There are many ways to treat intervertebral disc problems. Current methods focus on fusing adjacent vertebrae together or using partial or total prosthetic disc implants. In a spinal fusion procedure, some or all of the disc material is removed from the level to be fused. In particular, for interbody fusion procedures such as posterior lumbar interbody fusions (PLIF) or transforaminal lumbar interbody fusions (TLIF), a hole is made in the annulus and the interior portion of the disc is removed. Cartilaginous endplates are abraded to induce bleeding bone. In the place of disc material, an interbody fusion device is implanted. The fusion device is intended to maintain the height of the disc space and help stabilize the segment while fusion occurs. Fusion is achieved by implanting either bone harvested from another site in the patient (autograft) or an autograft replacement into the disc space.
Autograft replacement implants are associated with osteo-inductive factors and other bio-active agents that help promote osteoblastic formation. The ultimate goal of these implants is to promote bone growth that will connect vertebrae endplates to limit motions associated with the patient's lower back pain.
There are potential drawbacks to these sorts of spinal procedures. The surgically made hole in the outer band of the annulus fibrosis, if not properly closed or shielded, could act as a door for bone tissue and osteo-inductive agents to migrate from the intervertebral disc space into the area about the spinal canal. These migrations could eventually lead to pain in the patient associated with bone tissue protruding through the annulus fibrosis and pressing against spinal nerves.
Another possibility is bone tissue forming about the spinal canal due to osteo-inductive agents that have passed through the outer bands of annulus fibrosis. Depending on the type and amount of osteo-inductive agent used in the procedure, one could have bone or cartilage forming about the spinal cord, nerve roots, and surrounding muscles that can cause severe pain.
The prior art discloses methods or devices dealing with closing surgically prepared holes in the annulus fibrosis. U.S. Pat. No. 7,094,258 discloses methods of reinforcing the annulus fibrosis. The '258 patent further discloses inserting a barrier into the interior of an annular defect to seal it after an implant procedure. This patent prefers that the barrier be flexible in nature, being made from woven material such as Dacron™ fabric, Nylon™ fabric, collagen, synthetic polymers, and the like.
U.S. Pat. No. 6,371,990 discloses an apparatus and method for controlling vertebral motion. The '990 patent discloses reinforcing the inner walls of annulus fibrosis to support a prosthetic disc implant. The opening in the annulus fibrosis, referred in the '990 patent as flaps, is sewn shut and supported by a wire mesh that is screwed into adjacent vertebrae separated by the targeted disc space.
U.S. Pat. No. 6,454,804 discloses using a mixture of living annulus fibrosis tissue and the same obtained from a recently deceased person or animal donors to augment damaged annulus fibrosis in a patient. The '804 patent generally refers to gluing or suturing this annulus mixture to the inside or the outside of a patient's annulus.
Despite these procedures, there remains a need for a method that uses a tissue inhibiting matrix to ease complications associated with cell and osteo-inductive agent migration in the early phases of spinal repair.
The present invention overcomes the drawbacks of prior art by providing a novel method for preventing bone migration into soft tissue regions. Generally, a barrier is placed in the body between a first region and a second region. The barrier prevents migration of cells associated with the first region, for example osteoblastic cells, from migrating into soft tissue located about a second region.
A specific embodiment provides for a method which includes repairing an intervertebral disc. The method comprises forming a hole in the annulus fibrosis; removing damaged annulus fibrosis or nucleus pulposus from the intervertebral disc space; inserting an intervertebral disc implant into the emptied disc space; and closing the hole formed in the annulus fibrosis by delivering a growth-inhibiting matrix in or about the surfaces of the hole, such that the matrix acts as a barrier that prevents new tissue or agents associated with the implant from migrating into areas outside the intervertebral disc space. The new tissue may be, for example, bone.
In various embodiments, the method includes a matrix that cures in vivo.
In certain embodiments, the method includes a matrix that inhibits cells associated with the selected tissue type from attaching onto or into the inner surfaces of the growth-inhibiting matrix exposed to the center of the targeted implant region, such as the intervertebral disc space.
In certain other embodiments, the matrix inhibits the migration of osteo-inductive agents associated with the intervertebral implant from migrating into areas outside the targeted implant region, such as the intervertebral disc space.
In certain preferred embodiments, agents are associated with the intervertebral disc implant. The agents include at least one osteogenic agent selected from the group consisting of BMP (bone morphogenetic protein), BMP-2 (bone morphogenetic protein), bFGF (basic fibroblast growth factor), (insulin-like growth factor), PDGF (platelet-derived growth factor), rhBMP (human recombinant bone morphogenetic protein), TGF-β1 (transforming growth factor beta 1), VEGF (vascular endothelial growth factor), GDF (growth and differentiation factors), and any combinations thereof.
In other preferred embodiments, the matrix comprises at least one osteogenic protein-binding antibody selected from the group consisting of anti-BMP, anti-BMP-2, anti-bFGF, anti-IGF-1, anti-PDGF, anti-rhBMP, anti-TGF-β1, anti-VEGF, anti-GDF, and any combinations thereof.
In certain specific embodiments, at least one matrix osteogenic inhibitory agent is embedded into a bio-resorbable material and is time released.
In particular embodiments, the matrix prevents cells and osteogenic factors from migrating into areas outside the intervertebral disc space but allows fluid passage between the two.
In specific embodiments, the matrix is made from an anti-adhesion material that may or may not cure in vivo. The anti-adhesion material may include hyaluronic acid, carboxy methyl cellulose, gelatin, hydrogels, collagen gels, synthetic polymer formulations, or combinations thereof.
In other specific embodiments, the matrix further comprises an effective amount of at least one bioactive molecule capable of inhibiting cell attachment to the outer and inner surfaces of the matrix that is exposed to the implant or annulus fibrosis that is located in the disc space. The bioactive molecule capable of inhibiting cell attachment may comprise one or more anionic polymers such as, for example, dextran sulfate.
In some embodiments, the matrix may be delivered by injection into or about the hole in the annulus fibrosis that extends from the outer bands of the annulus fibrosis of an intervertebral disc into the areas in or about the nucleus pulposus located near the center of the intervertebral disc space. The matrix may be delivered to the hole by a syringe, needle, cannula, catheter, pump, or any similar device, or any combination thereof.
In certain specific embodiments, the growth-inhibiting matrix is bioresorbable within 2 to 6 weeks from delivery to the hole. Suitable materials include resorbable hydrogels, resorbable polymer compositions, resorbable copolymer compositions, resorbable polyion complexes, fibrin, collagen, gelatin, alginate, hyaluronate, Matrigel� membrane preparation, polyglycolide (PGA), glycolide-lactide copolymers (PGLA), polylactides (PLA), poly-L-lactide (PLLA), poly-D,L-lactide (PDLLA), ethylene oxide block copolymers with PLA, ethylene oxide block copolymers with propylene oxide chains, and combinations thereof.
In some embodiments, the implant is made from materials selected from the group consisting of polyethylene glycol (PEG), polylactides (PLA), polyglycolide-lactide copolymer (PLGA), polyvinyl alcohol (PVA), collagen sponge, gelatin, gelatin sponge, collagen, fibrin gel, and combinations thereof.
Another aspect provides a kit comprising a composition capable of forming a growth-inhibiting matrix and an implant. In some preferred embodiments, the implant is an intervertebral disc implant. The kit may further comprise a delivery device to deliver the growth-inhibiting matrix. The delivery device may be a syringe, needle, cannula, catheter, pump, any similar device, or any combination thereof. In some embodiments, the kit further comprises an osteogenic inhibitory agent for the growth-inhibiting matrix. In other embodiments, the kit further comprises a bioactive molecule capable of preventing cell attachment to the growth-inhibiting matrix. In yet other embodiments, the kit further comprises an effective amount of a bioactive molecule, associated with the implant, that is capable of inducing cell growth, cell migration, or cell attachment.
The terms "Growth-inhibiting matrix" and "matrix" refer to a collection of materials that may cure in vivo and act as a barrier against cellular attachment and migration of growth factors, such as osteo-inductive factors.
The terms "Surgically prepared hole" and "hole" refer to holes made in or about surgical target areas, for example a hole made in the outer bands of annulus fibrosis that extends into the area about the nucleus pulposus of an intervertebral disc.
The term "Interbody device" refers to a part of an intervertebral implant that is associated with promoting bone formation via osteo-inductive factors.
The term "Implant" refers to any object that is designed to be placed partially or wholly within a patient's body for healing purposes or artificial structural support, for example intervertebral disc implants and the like. The object is placed in the body and may be made from biologically compatible materials (e.g., medical-grade stainless steel, titanium, and other metals; polymers such as polyurethane, silicon, polylactic acid (PLA), polyglycolic acid (PLGA); and other materials); other materials that are exogenous, some materials derived from animals (e.g., "xenografts" such as whole animal organs; animal tissues such as heart valves; naturally occurring or chemically-modified molecules such as collagen, hyaluronic acid, proteins, carbohydrates, and others); human donor tissues (e.g., "allografts" such as whole organs; tissues such as bone grafts, skin grafts, and others); or from the patients themselves (e.g., "autografts" such as saphenous vein grafts, skin grafts, tendon/ligament/muscle transplants).
From this point, various embodiments of the invention are described. Although the present methods are primarily intended to prevent migration of bone tissue or osteo-inductive agents from the intervertebral disk space into the outer bands of the annulus fibrosis and the areas of the spinal canal surrounding the spinal cord, there are no intentions for the use of these words to limit the scope of the invention for uses in the human body. Any and all use of specific language and references are simply for detailing different embodiments of the same.
In addition, and despite explicit reference to only the following embodiments, any and all alterations and further modifications of the invention, as would occur to one having ordinary skill in the art, are intended to be within the scope of the invention. A non-limiting example is the prevention of tissue adhesion ingrowth about the spinal area after spinal fusion procedures.
Annulus Fibrosis and an Anti-Growth Matrix
A method for closing a surgically prepared hole in the outer band of annulus fibrosis is shown in
The implant 7 may include growth agents and, in particular, may include osteogenic growth agents such as BMP (bone morphogenetic protein) and rhBMP, particularly BMP-2 and rhBMP-2; bFGF (basic fibroblast growth factor); IGF-1 (insulin-like growth factor); PDGF (platelet-derived growth factor); TGF-β1 (transforming growth factor beta 1); VEGF (vascular endothelial growth factor); GDF (growth and differentiation factor); and combinations thereof.
The implant 7 as shown in
After the surgeon inserts the various components 11, 13 of the implant 7 into the cleaned disc space 2, the hole 3 may be closed by delivery of a growth-inhibiting matrix 15 to the area in or about the hole 3. The matrix 15 can be a non-porous tissue adherent gel, a bio-resorbable polymer, or the like, that cures in vivo. In any event, the matrix 15 acts as a barrier, either physically or in combination with active components, to prevent or inhibit migration of tissue and growth factors from the region 2 associated with the implant 7.
The matrix 15 may be injected into the disc space located in the posterior section of the spine, for example the posterior region of the outer annulus fibrosis band 5 where the surgically prepared hole 3 is located, or, if the surgery is of the anterior sort, the outer anterior region of the annulus fibrosis band 5. The matrix 15 may be injected, for example, into the annular fibrosis 5 from the outer edge 9 of the annular fibrosis 5 to about 2 mm to about 5 mm into the annular fibrosis 5. This method may be well suited for interbody fusion procedures about the lumbar region of the spine, but it is within the scope of the invention whereby the matrix 15 can be used in other regions of the spine.
The surgeon can determine the amount of growth-inhibiting matrix 15 to deliver in order to sufficiently seal the surgically prepared hole 3. Preferably, the method includes delivery of enough matrix material 15 to seal the hole 3 such that the cured matrix 15 is larger in area than the size of the hole 3. Some portion of the matrix 15 may abut and cure onto healthy fibrocartilage associated with the outer annulus fibrosis band 5. The matrix 15 will seal the bio-environment 2 of the implant 7 from the epidural environment 4 of the spine or other bio-environments surrounding the vertebral body. The matrix 15 preferably only fills the open area of the annulus without penetration into the disc space beyond about 2 to 5 mm so as not to interfere with desired bone formation and fusion. The matrix 15 thus forms a barrier between two regions 2, 4. The first region 2 may extend from the outer bands of annulus fibrosis 9 into the center of the intervertebral disc space, where the implant 7 rests. Typically, bone tissue grows near the surfaces of the implant 7 in the first region 2. The implant 7 may have growth factors to encourage the formation of the selected tissue type, i.e. bone, such as those present within the bone graft 11, which may have BMP.
The matrix 15 may inhibit attachment of selected tissue cells, i.e. bone tissue, onto or into surfaces of the growth inhibiting matrix 15 by forming the matrix from anti-adhesive materials to prevent the same. Alternatively, the outer surfaces of the matrix 15, and particularly those regions of the outer surfaces that are exposed to the first region 2 in which growth of the selected tissue is desired, may be coated or otherwise provided with an anti-adhesive material.
Suitable Materials for the Anti-Growth Matrix
A suitable matrix 15 can be made, in whole or in part, from various materials, where non-limiting examples are bio-resorbable polymers, non-bio-resorbable polymers, natural polymers, anti-adhesion gels, and any combinations thereof.
Suitable examples of bio-resorbable polymers may include, without limitation: poly(alpha-hydroxy acids), poly(lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PG), polyethylene glycol (PEG), conjugates of poly(alpha-hydroxy acids), polyorthoesters, polyaspirins, polyphosphagenes, collagen, starch, chitosans, gelatin, alginates, dextrans, vinylpyrrolidone, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (polyactive), methacrylates, poly(N-isopropylacrylamide), PEO-PPO-PEO (pluronics), PEO-PPO-PAA copolymers, PLGA-PEO-PLGA, silk, and combinations thereof.
Suitable non-limiting examples of synthetic non-bio-resorbable polymers include hydrogels such as PVA, delrin, polyurethane, polyethylene, co-polymers thereof, and any combinations thereof.
The matrix 15 may be made from suitable anti-adhesion materials, which may include, without limitation, hyaluronic acid, carboxy methyl cellulose, gelatin, hydrogels, collagen gels, synthetic polymer formulations, and combinations thereof.
The matrix 15 may be made from natural polymers including, without limitations, collagen, elastin, silk, hyaluronic acid, chitosan, and any combinations thereof.
The growth-inhibiting matrix 15 may cure in vivo and may be bio-resorbable within a time frame that is sufficiently close to the time release of the osteo-inductive factors 11 associated with the implant 7, which may preferably be from about two to six weeks after delivery of the matrix 15 to the surgically prepared hole 3. However, a matrix 15 that seals the hole 3 for a longer time than stated may also be employed.
Additives Associated with Anti-Growth Matrix
In certain embodiments, the matrix 15 may include an agent to prevent cell attachment and infiltration. In certain embodiments, the agent to prevent cell attachment and infiltration may be an anionic polymer or polysaccharide. Suitable polysaccharides may include, without limitation, dextran sulfate and other carbohydrates.
In certain embodiments, the matrix 15 may include at least one anti-osteo-inductive antibody, anti-BMP antibody, or the like. The anti-osteo-inductive antibody, anti-BMP antibody, or the like may be embedded within the entire volume of the matrix material 15 upon in vivo curing or may be placed as an external coating on the matrix 15. It is preferred that the matrix 15 retains the anti-osteo-inductive antibody such that osteoinductive agents moving through the matrix from the disc space will be bound and inactivated to prevent bone formation beyond the matrix outside of the disc space.
Suitable anti-osteo-inductive antibodies may include without limitation anti-BMP, anti-BMP-2, anti-bFGF, anti-IGF-1, anti-PDGF, anti-rhBMP, anti-TGF-β1, anti-VEGF, anti-GDF antibodies, and any combinations thereof.
Dosage of Additives Associated with the Matrix
Typically, the bio-active additives within the matrix 15 will not be greater than about 1% to 10% of the total matrix 15 volume once cured in vivo. The additives can be added to the matrix 15 before or during delivery to the hole 3. Any suitable range for the bio-active additives may be used, and are typically in the range of about 0.01 mg per cc to about 100 mg per cc. In other embodiments, from about 0.1 mg per cc to about 50 mg per cc may be employ. In yet other embodiments, from about 0.1 mg per cc to about 20 mg per cc of a bio-active additive may be employed. In certain advantageous embodiments, about 1 to 3 mg of a growth factor (BMP, for example) per cc of carrier (for example purified collagen and a biphasic calcium phosphate (BCP)) may be sufficient, for example, to heal bone defects. Accordingly, a range of about 0.1 mg to about 12 mg of an osteo-inductive additive (BMP, for example) may be preferred for many intervertebral implants 7. As such, it may be desirable that the growth-inhibiting matrix 15 have anti-osteo-inductive additives in an amount sufficiently close to the 0.1 mg to about 12 mg of osteo-inductive additives associated with the intervertebral implant 7. One example embodiment of the matrix 15 comprises between about 2 mg and about 3 mg per cc, e.g., about 2.5 mg anti-adhesion gel/cc of carrier.
Delivery of Matrix into the Outer Annulus Fibrosis Band
After an implant 7 has been passed through a hole 3 in the outer portions of the annulus fibrosis 9 and inserted into a disc space 2, the hole 3 may be sealed by a mode of delivery that preferably achieves a local accumulation of the matrix 15 in or about the posterior portion of the annulus fibro-cartilage that abuts the spinal cord 17.
Delivery of an effective amount of the matrix 15 may be provided by a controlled administration system comprising a pump or similar device and an optional catheter connected to the pump to provide a channel for the matrix 15 to be transported from the pump to the targeted annulus fibrosis area 3, 9. The pump may provide for controlled release and deposition of the matrix 15 about the outer disc region, for example the posterior portion of the annulus fibrosis band 5 abutting the spinal cord, at a rate that substantially matches a targeted volumetric release rate profile selected by a surgeon.
A distal end of the catheter may be placed about the target area 3, 9. The matrix 15 may thus be directly released into the disc region associated with the hole 3 in the annulus fibrosis 9 that needs closing. The proximal end of the catheter may be fluidly connected to the pump. The pump is preferably disposed externally to the body while the matrix is delivered to the target area 3, 9, and may be provided with one or possibly more catheters to deliver the matrix 15 to appropriate target sites.
Other devices suited for drug delivery may also be used to seal the surgically prepared hole 3 about the outer portions of the annulus fibrosis 9. For example, a syringe may be a particularly advantageous delivery device for the matrix material 15.
To position the matrix 15 at the target region 3, 9, the distal end of the matrix delivery device, be it a catheter, a needle or the like and from which the matrix material 15 is ejected, is preferably positioned adjacent to the opening 3, a few centimeters away from the opening 3, or even up to about 5 mm into the opening 3. As the matrix material 15 is ejected from the distal end of the matrix delivery device, the surgeon may move the position of the distal end to dispose the matrix material 15 around the region of the opening 3, and even within the opening 3. A sufficient amount of matrix material 15 should be disposed in and around the opening 3 to provide an adequate seal.
Having generally described methods for using a growth inhibiting matrix to benefit intervertebral disc procedures, the following specific example is offered for purposes of illustration and only for illustration. There is no intention to limit the invention from the following words.
A method for using a growth inhibiting matrix for interbody spinal fusion may be prepared and delivered as follows. Exposure of the posterior annulus of the disc space to be treated is first achieved. Then, a hole is cut in the annulus, and a volume of disc material is removed to allow for placement of bone graft or bone graft substitute and interbody fusion device(s). After placement of the interbody fusion device, a growth-inhibiting matrix is applied from a syringe just inside the annulus opening and around the hole through which the interbody device was implanted.
Another method of using the matrix of the present invention includes using the matrix to prevent unwanted migration of growth agents or cells from sub-chondral bone into hyaline cartilage tissue as shown in
An osteogenic implant 30, of any suitable type, is thus disposed within the defect 20. It is preferred that implant 30 completely fills the defect 20. The osteogenic implant 30 may include, for example, therapeutically effective amounts of an osteoinductive growth factor, such as rhBMP-2, embedded within a bioresorbable scaffolding, such as a mixture of collagen and calcium phosphate. As the scaffolding is absorbed by the host bone 22, the growth factor is released. High concentrations of the growth factor may encourage bone growth within the defect 20, thus encouraging the autologous bone 22 to migrate into and fill the defect 20; but, it can also induce bone formation within local soft tissue 40, which is not desired.
To prevent bone formation within the surrounding soft tissue 40, for example hyaline cartilage, a surgeon may dispose a growth-inhibiting matrix 50 over the opening 24 of the defect, such as by injecting the matrix 50 over the opening 24 after the implant 30 has been placed into the defect 20. The growth-inhibiting matrix 40 is thus positioned between the defect region 20, in which bone growth is desired, and the soft tissue region 40, in which bone growth is not desired.
The growth-inhibiting matrix 50 prevents migration of bone cells through the opening 24 and further prevents migration of the growth factors within the implant 30 into the soft tissue 40. The matrix may additionally be bioresorbable. As a result of the matrix 40, relatively high concentrations of the growth factors or agents may be kept within the defect 20 without causing undesired bone growth within the soft tissue 40.
The matrix may further comprise at least one inhibitory agent that blocks or antagonizes the growth effects of the growth agent, such as anti-BMP, anti-BMP-2, anti-bFGF, anti-IGF-1, anti-PDGF, anti-rhBMP, anti-TGF-β1, anti-VEGF, anti-GDF, and the like. The inhibitory agent may be disposed throughout the volume of the matrix 40.
Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is understood that many modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the following claims.
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|Baxter International Inc.
|Method for directed cell in-growth and controlled tissue regeneration in spinal surgery
|Rapp, Susan M., New anti-adhesion gel could help make spine revision surgery easier, Apr. 2006, OrthoSuperSite, http://www.orthosupersite.com/view.aspx?rid=16436.
|Citing Patent
|Filing date
|Publication date
|Jan 25, 2012
|Feb 4, 2014
|James W. Ogilvie
|Method of treating scoliosis using a biological implant
|Jul 25, 2011
|Apr 8, 2014
|Aleeva Medical Inc.
|Alleviate back pain with lactic acid inhibitors
|Feb 3, 2014
|Jun 21, 2016
|Michael R. Schramm
|Method of treating scoliosis using a biological implant
|Jun 20, 2016
|Apr 18, 2017
|Michael R. Schramm
|Method of treating scoliosis using a biological implant to scoliosis
|Jul 25, 2011
|Jan 26, 2012
|Jeffrey Eric Yeung
|Alleviate back pain with lactic acid inhibitors
|U.S. Classification
|623/17.16, 623/17.11, 606/279
|International Classification
|Cooperative Classification
|European Classification
|Aug 6, 2007
Owner name: WARSAW ORTHOPEDIC, INC., INDIANA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PECKHAM, STEVEN M.;REEL/FRAME:019655/0929
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The religious soul who believes without stiff breeze humility pitfalls, and one that unwisely imagines hover in high perfection, need help with thesis full life unites e before having tasted the benefits enough life Purgat e prepares to bitter surprises. Fly our wings like birds sky, we take off our heart of this land where the attach so secret links. Even add, by security measure, seo content writing services a last pair of fins made perseverance consistency, under that fear God, his love, and eternity which will be added! The fervor is a favor to ask daily. She easily blooms in garden of Christian life fully lived. It ensures success all our climbs uphill road on perfection it mainly provides our final orientation, beyond good top reassuring death to remain that Jesus has gone to prepare. In his Sermon on F Fourth Ascension, St. Bernard track us track our ascent to God, having reminded us a few distinctions.

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Antonia Dean
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Antonia Dean is the Vice President of External Relations at Venture for America, a two-year startup fellowship for recent college graduates. Prior to joining the startup world, Antonia was a brand and marketing strategist in the cosmetics industry, having worked on and created new brands for Calvin Klein, Vera Wang, and Michael Kors, to name a few. Antonia received her Bachelor of Science in Business Administration from Florida A&M University and her Juris Doctor from Harvard Law School. Antonia lives in Harlem where she enjoys trying the neighborhood's newest restaurants and testing out the playgrounds with her toddler son, husband, and 5 pound Yorkshire Terrier, Furious Styles.
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The Rutgers Scoutcast is a weekly podcast for Rutgers fans of all varieties. In our latest episode, we speak to a pair of out-of-star Rutgers recruiting targets. Miami (Fla.) Northwestern defensive back Rachad Wildgoose Jr. committed to Rutgers last week, and four-star offensive lineman Blaine Scott put the Scarlet Knights in his final five. Then, Scout national recruiting analyst Brian Dohn stops by to talk recruiting, spring football and more.
Please rate, review and subscribe.
To jump right into the action, a timesheet is available below for your convenience.
0:00 - Open
5:45 – Rachad Wildgoose Jr. Interview
13:50 – Blaine Scott Interview
22:10 – Out of State Recruiting
29:30 – Spring Game Preview
36:15 – Rutgers Scoutcast Mailbag – QB Recruiting & Salsa, Seltzer?
42:28 – Close
For a full show archive, click below.


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T is silent, and so is this page. You didn't read about it here. In fact, you're not reading this, you're feeling it. A letter of The Alphabet. Wordinistas may want to tell you its place in the alphabet, but that's not important unless you're a librarian and like books. It has been missing from Stephen's last name for as long as he can remember. Stands for both "This is The Colbert Report" and "truthiness."
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Spaceland & Laserium Present
Laserium Led Zeppelin - A Laser Tribute
Sun April 23, 2017
Doors: 8:30 pm
Show: 9:00 pm
The Regent Theater
Los Angeles, CA
$16.50 - $18.00
Purchase Later Double Feature Pink Floyd / Led Zep Pass Here
This event is all ages
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Laserium, and indeed the laser light show itself, was born in the late 60's and early 1970's. Ivan Dryer, then a film maker, was treated to a lab demonstration of a new multi-colored laser at Cal Tech. He was so taken by the purity and intensity of the colors that he decided to make a film and set the beautiful patterns to music. His film, Laser Image, disappointed him though. Even though it was an enchanting visual piece, the lasers, as caught on film, lacked the original sizzle they had when seen live. Convinced that one had to experience laser light live, Ivan founded Laser Images in Van Nuys, California. He gathered together a group of clever optical, mechanical, and electrical engineers and artists who, in the next two years had crafted an advanced laser projector and choreographed the original Laserium show.
Presenting the idea to the Griffith Observatory and Planetarium landed Ivan a temporary concession operating permit from the city of Los Angeles. Laserium opened its doors on November 19, 1973. Laserium expanded to many locations in the United States and abroad and has been experienced by over 20 million people. Laserium continues to produce new laser shows for tours and for music listening events. The company also produces outdoor laser shows, night club, trade show, and rock concert laser effects, and special effects for motion pictures and television.
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2017 © Spaceland Presents


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They are just baby-faced kids, some too young to even drink, but these call-ups already are making memorable impacts.
In one single day Wednesday, one call-up hit a grand slam, another scored the winning run, another won his first game and yet another found himself starting in the middle of the lineup in a pennant race.
Take a look:
Also, keep an eye on:
By Bob Nightengale
Daily Pitch is a baseball fan's destination for breaking news, emerging trends and enlightening banter. With a veteran group of reporters positioned in three time zones, we provide a balanced, comprehensive glimpse at our national pastime, with a nod to both the passion and complexities that make the sport irresistible to many. More about our reporters


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It also had a motorcycle called Black Dog that it uses to evade the attacks of Kamen Rider Wizard, but it was destroyed by Wizard in their second fight.
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- Gate: Kazuo Tajima
- Episodes: 2-3
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Gold 2016 Hollywood Film is a New American offence, action and full of adventure movie. Gold is directed by Stephen Gaghan and written by Patrick Massett and John Zinman as a writing sample and succeed by Paul Haggis. So, the location of movie is in New York, New Mexico and Thailand. The movie performer Matthew McConaughey as Kenny Wells, Bryce Dallas Howard as Kay, Édgar Ramírez as Michael Acosta, Timothy Simons as Jackson, and Joshua Harto as Lloyd Stanton, Corey Stoll as Brian Woolf. After all, main photography of film production is start on June 29, 2015. Gold 2016 Hollywood Film is inspired by a real story. An unexpected partner venture to the Indonesian jungle in search of gold.
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Gold 2016 Hollywood Film:
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After in August 2011, Variety announce that Christian Bale was being eyed for the main character , and it was one of some projects he had to select between the same time.In March 2012, Mann happy about the task due to his attachment in the making of the film Big Tuna and an untitled cyber crime movie (aftre titled Blackhat).
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Selection of Cast:
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Édgar Ramírez was attach to the cast on March 18, 2015, to perform the character of geologist Michael Acosta. On March 30, 2015. Then, Weinstein Company get the movie's US administration rights for Fifteen Millon Dollars. So, the movie would publicize domestically through firm's TWC-Dimension label. On May 15, 2015, Michelle Williams was set to actor alongside McConaughey, to perform his role's wife. Joshua Harto select-on on June 3, 2015 to perform Lloyd Stanton, the businessman's bank account manager.. Michael Landes also include in the cast on June 29, 2015 to perform in the movie. Finally, on August 28, 2015, Bryce Dallas Howard committed to cast in the movie for the female main character of Kay, Wells' longtime girlfriend, in the place of Michelle Williams.
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- Michael Landes as Binkert
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Gold 2016 Hollywood Film is plan to screen on December 25, 2016, by TWC-Dimension.
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Capital City Pride in Olympia, Washington is a series of events culminating with Olympia Pride day. The festival celebrates the region's Gay, Lesbian, Bisexual and Transgendered (GLBT) community. The Pride festival is held at Sylvester Park in downtown Olympia. Traditionally, The Capital City Pride parade and festival has been on Saturday, but was moved to Sunday in 2007. The 2008 festival and parade occurs June 22. State Sen. Joe McDermott (D) is the 2008 grand marshall.
Pride Day is geared to honor civil rights gains in the past year, highlight youth activists and honor long-time activists for their commitments. Entertainment and the Pride Parade are highlights of the day. Approximately 6,000 people attended the 2007 Pride day. The festival is funded through private fundraising and sponsorship, grants and tourism funds.
The organization began under the auspices of Rainbow Center Olympia in 1991, and as of 2008 is an independent group with a committee and elected officers. The organization's annual budget is approximately $30,000.
External linksEdit
Lodging Tax Fund proposal[1] Committee and organizational structure [2] City of Olympia event permit [3]
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Workshop Report Day Two
painting by artist Karen Margulis
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Images may not be reproduced without the permission of the artist.


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Israel Ch. 10 Tuesday reported that the United States has withdrawn objections to the appointment of Ron Dermer as the next Israel ambassador to the U.S., replacing Michael Oren. Back in December, rumors circulated that Dermer would be the next ambassador after the Israeli daily Makor Rishon reported that Oren had requested to end his… Read More
'Can't The Jews Have One?'
It was a tragedy that is hard to forget. In March 2011, a terrorist infiltrated the town of Itamar and slaughtered five members of the Fogel family, including a 3-month-old baby girl and two other children. The killings were discovered by 12-year-old Tamar Fogel. Volunteers from Israel's emergency cleanup organization ZAKA, who arrived on… Read More
Hand in Hand
Ben-Gurion University of the Negev recently graduated its first class of Jordanian and Israeli students who completed a special joint-emergency medicine BA program earlier this year. The first graduating class at the Israel-Jordan Academic Emergency Medicine Collaboration included 54 graduates who spent three years studying emergency medicine and medical response. One part of the curriculum… Read More
Google Confirms Waze Acquisition
Google confirmed its acquisition of the Israeli navigation company Waze. In an announcement Tuesday on the company's official blog, Google Vice President Brian McClendon did not indicate the price Google paid to acquire Waze, though reports put the figure at $1.1 billion. McClendon said the product development team at Waze, a free downloadable navigation app… Read More
Peres, Abbas call for peace at World Economic Forum
JTA Wire Service Israeli President Shimon Peres and Palestinian Authority President Mahmoud Abbas called for peace at the World Economic Forum in Jordan. Peres in his address Sunday evening said, "I am here to express the hope and desire of the Israeli people to bring an end to the conflict and a beginning to a… Read More
U.S. publishes details of secret Israeli military base
JTA Wire Service The U.S. government published on a federal website details of a top-secret base in Israel to house the Arrow 3 missile defense system. A 1,000-page detailed description of the project, to be built by the United States for Israel, was published on a federal business opportunities website in order to allow contractors… Read More
WHO approves Israeli-developed circumcision device
JTA Wire Service The World Health Organization approved an Israeli-developed non-surgical circumcision device that could soon be used throughout Africa to help control AIDS. PrePex, a disposable and easy-to-use device made of rubber bands that obviates the need for anesthesia, stitches or a sterile setting, received WHO approval on Friday, The New York Times reported.
Computer network to help break Cairo Genizah codes
JTA Wire Service The Friedberg Genizah Project will use a high performance computer network at Tel Aviv University to break the codes of the Cairo genizah. The project, announced on Sunday, will match up pieces of some 200,000 ancient manuscripts discovered more than a century ago in the genizah. More than 100 linked computers at… Read More
Beersheva bank attack spurs gun reforms in Israel
JTA Wire Service Israel would require security guards to leave their weapons at work under gun reforms unveiled in the aftermath of a Beersheva bank attack that killed four. Public Security Minister Yitzhak Aharonovitch announced the planned reforms on May 21, the day after a former Border Police captain's rampage at a Bank Hapoalim branch.
Electric car company Better Place files for bankruptcy in Israel
JTA Wire Service The electric car company Better Place filed for bankruptcy in an Israeli court. In a motion filed Sunday in Tel Aviv's Central District Court to dissolve the company, Better Place said it was looking for a temporary liquidator. The company, based in Palo Alto, Calif., fired about half its staff last October…. Read More


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Butterick 6373; ca. 1980s: Misses' Dress. Very loose-fitting, pullover dress, below mid-knee or mid-calf, has dropped shoulders, low waist bodice. A-line skirt pleated or gathered into inset band, side button closing and short or long sleeves with bands. B: cap sleeves and sash.
Links to reviews/blog postsEdit
Add a photo to the gallery by clicking the "modify" button below.
[insert your username, and make sure your preferences allow for people to contact you via e-mail. Do not list your email address here!]


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I want to test my EA in offline mode, but having trouble getting the EA to calculate correct lot sizes when in offline mode as you know MarketInfo returns 0 values when in MT4 is in offline mode.
There are other posts about this issue, but none of them seem to have a solution for this. One of the latest: https://www.mql5.com/en/forum/150991
There must be a workaround this as so many people talk about testing in offline mode?
Here is what I get when in offline mode:
Please help


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Red Hat Updates JBoss SOA
Linux provider Red Hat announces new versions of its JBoss Enterprise SOA Platform 4.3 and JBoss Operations Network 2.1.
The Enterprise Service Bus (ESB) component of the JBoss SOA Platform 4.3 should provide new gateway listeners, a declarative security model and additional scripting languages. New rules features include stateful rules, decision tables and support for rule agents. The Operations Network 2.1 component includes, among other things, a remote monitoring facility. Better integration with the ESB should facilitate monitoring of the service bus.
Red Hat started a massive campaign in February to promote its open source JBoss Java middleware product, now available in community and commercial versions. Included in these offerings were the cost-based Enterprise SOA Platform and the Operations Network 2.0, another cost-based management platform for the entire middleware palette. The JBoss package with its Red Hat Linux underpinning targets the SOA market.
Issue 201/2017
Buy this issue as a PDF
Kolab Now Integrates Collabora Online
Kolab Now subscribers now have access to Collabora Online.
Endless OS, a Distribution Without Internet
A new version of Endless OS has been released.
GitHub Announces Open Source Friday Program
They encourage people to take time out and work on open source projects on Friday.
System76 Announces Their Own Distro, Pop!_OS
Pop!_OS is based on Ubuntu and uses the Gnome stack.
Linus Torvalds Talks About His Motivation
He never tires of working on the Linux kernel.
Debian 9 Stretches Its Wings
The new release of Debian has a very strong focus on security.
Trojan Turns Raspberry Pi into a Cryptocurrency Mining Device
Two trojans in the wild are targeting Linux machines.
Fedora 26 Beta Comes with New Features
The workstation comes with the latest Gnome desktop environment and support for many application build systems.
Raspberry Pi Foundation Merges with CoderDojo Foundation
The two foundations join forces to expand their efforts to reach young people.
Samba Security Hole Patched but Risk is Bigger
Millions of devices that use Samba Server are vulnerable to attacks.


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This article is a list of the radio conversations in the non-canon game Snake's Revenge. Similar to Metal Gear, the conversations in this game are completely room oriented and one-sided. In addition, also similar to in Metal Gear, the conversations are also extremely limited in nature, unlike in future games where they give direct details about things pertaining to the mission, as well as give some background and miscellaneous information. It is technically the first Metal Gear game to feature the faces of Solid Snake's contacts, which would later be implemented canonically in Metal Gear 2: Solid Snake onward. The player will also need a dry cell to recharge the radio at one point in the game.
Helicopter pilot
Pilot: Snake, the pur-pose of your mission is to infiltrate the enemy strong-hold. You must collect information from your co-workers.
Bad news, Snake
Pilot: Snake, I have bad news for you. You went into the enemy's air space. We can't help you anymore. See you at the meeting point after the military operation is over. Good luck!!
See you soon
Pilot: Hey, Snake. Are you OK? I'll see you soon.
Transmitter activated
Pilot: I set the transmitter. Climb up the deck and use the radar. Hurry up!
Metal Gear 2
Pilot: Congratulations!! Metal Gear is destroyed. But, we have confirmed the existance [sic] of Metal Gear 2. Now Nick is missing. Contact your person at the enemy's base.
Secret Entrance
Pilot: The secret entrance must be somewhere on the grounds.
Reinforced door
Pilot: Snake, follow Jennifer's instructions on entering secret plant. [sic] Use cop-ter missiles to blow up the wall to enter. The spot is marked by a flare. You must not fail.
Nick Myer
John's on the ship
Nick: Lieutenant! It appears that John is a hostage on the ship.
Operation's a go
Nick: Sorry about this late communication. The military operation is a "go."
Nick: Lieutenant, it was careless of me. I, uh....
John Turner
Enacting the plan
JT: Lieutenant, I arrived at Point A. Let's put the plan into effect. Good luck infiltrating the enemy's base.
John's location
JT: I've been captured in the transport train but have set up the transmitter.
"No traps"
JT: There is no trap on the train.
Third car
JT: I'm in the third car. There are no enemies here.
Important information
Jennifer: You can reach me at the main base. I have some important information.
Nick's ahead
Jennifer: Lieutenant, Nick is coming to us ahead of you. Follow him.
Metal Gear 2 plans
Jennifer: I found the plans for Metal Gear 2. The enemy's commander is going to launch nuclear missiles all over the world. Hurry up!
Commander's location
Jennifer: The commander is located on the top level of this base.


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Pepper - Hungarian Hot Wax
|Share the ♥
Pepper (HOT), Hungarian Hot Wax (100% Heirloom/Non-Hybrid/Non-GMO)
Details | The Scoville Heat Units (SHU) for this pepper measures 750 to 3,000.
- Hungarian hot wax derived its name because it was originated in Hungary and has a waxy color that resembles bees' wax
- This is a great all purpose pepper for processing and pickling, good for the home garden
- Easy to grow
- Tolerates heat extremely well
- Grows well in containers and raised bed gardens
Day to Maturity | 75 days
Hot Pepper Seeds | Keep your soil moist and about 75°F. Space plants about 18" apart and 1/4" deep.
Click here for complete Hot Pepper grow guide
✓ Pure NON-Genetically Modified seeds ✓ 100% NON-Hybridized seeds ✓ 100% Heirloom/Open-Pollinated seeds ✓ 100% Raw & Un-treated seeds
Pepper - Hungarian Hot Wax has a rating of 5.0 stars based on 2 reviews.


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"THE conventional army loses if it does not win. The guerrilla wins if he does not lose." Henry Kissinger's observation, made during the Vietnam War, should be haunting Hezbollah, the Middle East's most capable guerrilla force, as it becomes embroiled in an increasingly costly effort to save the Assad regime.
Read Full Article »


text:
Your Store:
item(s) totaling $
|This product doesnt fit any of your saved vehicles
|Check Fit for another vehicle
REVIEW SNAPSHOT®by PowerReviews
Reviewed by 3 customers
Comments about Mr. Gasket Competition Style Wire Loom Kit:
The best thing about the loom kit is the craftsmanship. The material is made to sculpt around the valve covers for a clean nice appearance while holding the spark plug wires up above the headers to prevent the wires from burning into like stock looms will do.Mr.Gasket did a great job designing and engineering the looms. The color does not fade from the heat of the engine like ones I've used in the past . I would definitely purchase the looms again. Great price on a great performance product. thanks mr gasket!!
Comments about Mr. Gasket Competition Style Wire Loom Kit:
Had to be bent to fit.
Best Uses
Comments about Mr. Gasket Competition Style Wire Loom Kit:
They're nice for the price. My only complaint is the holders for 4 wires can not go on the bracket. Other than that. A good product.
Do you have questions about this product?
Ask a question, get answers from real customers and in-house experts. For further assistance, please review your support options on our Contact Us page.
Q:how are these supposed to be installed on a GMC 305? i purchased them but no illustrations or directions.
1 answer
A:Hi Joe, glad to help you! Please visit this installation instructions link for the wire loom kit. URL - http://prestoliteperformance.com/media/instructions/mrgasket/Mr_Gasket_instructions_spark_plug_wire_loom_kit.pdf
Q:Will this work for a 95 f150 with the 5.8L engine?
1 answer
A:I'm glad to be of assistance! This product is not specifically made for your vehicle. This will fit 7 mm, 7.5 mm and 8 mm plug wires.
Q:will these fit 10mm wires
1 answer
A:The specification of this part Mr. Gasket Spark Plug Wire Loom Kits, Part No. 9880 manufactured by Mr. Gasket: Wire Separator Material: Plastic, Wire Separator Finish: Blue, Plug Wire Attachment Style: Clip-in, Brackets Included: Yes, Bracket Attachment Style: Valve cover bolts, Bracket Material: Steel, Bracket Finish: Chrome plated, Wires Routed: Over valve cover. NOTE: The Kit contains eight 2-hole looms, 4 brackets, and two 4-hole separators. These wire dividers fit 7 and 8mm wires with ease.
Q:will these work on center bolt valve covers
1 answer
A:We will need more information including the year, make, model, and engine size of your application before we can make a suggestion. Please call us at 1-877-ADVANCE (238-2623) and we would be more than happy to further assist you.
Q:will these work with center bolt valve covers
1 answer
A:To further assist you on this question could you please provide your vehicles year, make model, and engine size.


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Hey everyone,
A question to themeforest buyers, do you still care about IE7 ? will I experience a drop in sales if I ditch the support for IE7 ?
Im asking this after the staff decision that IE7 support is no longer required.
Yes, I will still support it.
We contribute to the development of web sites around the world, when we throw the IE7 . They slow all our development process. We are professionals and we want our customers to be happy without using IE7 !
NO ! I think we should move ahead with technology. Even analytic says, percentage of IE 7 users around the globe is around 3-4%
No, giving IE7 up!!
Look.. it's a simple fact… even if IE7 support is not strictly required for themeforest approval, it IS still a web browser and people DO still use it… I don't care about W3C 's personal stats.
If the browser still exists and people are using it, then yes, it's your job as a web developer to support it. ESPECIALLY in the template/themes market.. because think about it, when you're developing sites for clients you have data available based on your client's user base to tell you which browsers are worth supporting, BUT in the themes market you have absolutely no idea who is going to be using your theme, who their users are or what browsers they will be using..
I really don't know why this is a topic that needs so much discussion.
QuadCodes said
Even analytic says, percentage of IE 7 users around the globe is around 3-4%
Opera is 2-3%, Safari is 3-4% ...
Its z-index problems which are the main problems with IE7 .
This buyer still needs IE7 support…unfortunately


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Micro Flakes Of The Night Earrings - Tainted Foil
Micro flakes of the night earrings in tainted foil colours, handcrafted from environment-friendly bioresin and brass findings. Real copper foil is embedded within the bioresin. The earring hooks are gold plated brass and nickel-free.
Designed and handcrafted in Singapore by Amado Gudek.
Dimensions of earrings - for one side:
Approximately 2.6cm across x 5cm long (including earring hook) x 0.25cm thick
Size of square pendent:
Approximately 1.9cm x 1.9cm
Please note that as each piece is individually handmade, small bubbles may occur naturally. Due to the spontaneous approach of mixing colours with bioresin, every item produced will have some slight variations in the shade, amount and position of colours. I.e. It will not be exactly the same as the one pictured in this listing.


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Full IP connectivity regardless of the underlying protocol.
Use this security logo:
Freeware is computer software that is available for use at no cost or for an optional fee.
Tutorial not found. Let know us about any useful video tutorial.
DNS configuration, VoIPv6, IPv6TV, Address Planning, gogoClient, IPv6 gaming, gogo6


text: Most of you have probably heard of little kuriboh's yugioh the abridges series. if not, look it up on his youtube channel, cardgamesftw if you like yugioh at all. Anyways, he set the trend for having abridged series for animes. my question is, does anyone know any good One Piece abridged series?


text:
British Airways Ill Pilots
January 18, 2012 by staff
British Airways Ill Pilots, British Airways has launched an inquiry after two pilots were taken ill on board a flight late last year. The illnesses was attributed to a lack of oxygen on the flight deck.
The BBC reports that British Airways (BA) have opened an investigation after two pilots fell ill on a flight between London, England and Glasgow, Scotland. The flight was on December 20 but the incident has only just been announced.
The Daily Mail reports that the captain and his co-pilot became light-headed as the plane climbed to 20,000 feet. This was 20-minutes into the flight. The pilots had to request that flight attendants came to the cckpit to assist them.
Most commercial aircraft are pressurized at a maximum cabin altitude of 8,000 feet, which allows people to breathe normally. However, if the cabin pressurization level reaches the equivalent of 14,000 feet or higher then there is an oxygen shortage which triggers the release of oxygen masks.
Due to the incident the jet was forced to make an emergency landing and the passengers were transferred to another aircraft. No one was hurt in the incident and the pilots recovered. The official line, as 9 News reports, given to the passengers at the time was that the aircraft had experienced "technical problems".
Please feel free to send if you have any questions regarding this post , you can contact on
Disclaimer: The views expressed on this site are that of the authors and not necessarily that of U.S.S.POST.


text:
|Ofir Schwartz - Tony is hard worker and also demand the same from other....
|Marius Motofei - I recommend Tony as a reliable professional. I have had...
About Dr. Tony W. Khatskevich
- Over 15 years experience in heading-up R&D organizations with a proven track
record in critical time-to-market deliveries.
- Over 20 years experience in development and design of SW and HW solutions,
including real-time and embedded environments, and building complex
multiplatform systems.
- Experience in implementing and managing Professional Services and assisting
Business Development activities.
- Extensive knowledge in managing and developing QC testing tools and
- Broad expertise in
Wireless/Cellular communication (3GPP, GSM/GPRS, WAP, 802.11x),
Data and IP security (IPSEC, PKI, VPN, PC/SC, SSL, DRM),
Networking (TCP/IP, UDP, HTTP, SMTP, RTSP, SNMP),
Video/Audio compression (MPEG-4, H.264/L, G.72x, DirectShow, WMV),
Digital Signal Processing (TI, ADI), with strong theoretical background in
computer science and mathematics.
- Vast practical experience in a wide range of applications, programming
languages (C/C++, Java, Assembler), development platforms (Windows, Linux,
UNIX, Win CE, VxWorks, pSOS) and environments (Visual Studio, .NET, Code
Composer, Platform Builder).
- Familiar with OOD/OOP, J2EE, J2ME, COM, MFC, SQL, Web and Client-Server
- Familiar with various chipsets (Intel, TI, ADI, Motorola, Siemens, Toshiba, Atmel).
If you notice offensive or incorrect information, please contact us.
Mr. Georgiy Shenderovich
Technology training @
Mr. Leedor Agam
Archon Technologies
Mr. Itsik Kissman


text:
Construction Manager
- Recruiter
- Ardmore Construction Limited
- Location
- London, Greater London
- Salary
- £75,000
- Posted
- 24 Jan 2017
- Closes
- 24 Feb 2017
- Sector
- Engineering
Job Profile: To supervise, direct and execute operations on the assigned project to ensure it is completed safely, on time and within budget. Key Areas of Responsibility: Management of All aspects of Health & Safety on siteEnsure any temporary works have the necessary design and are installed in accordance with the designProduce 2-week look ahead programmes for managers, operatives and sub-contractors working under you to ensure that the construction programme is achievedEnsure all operatives have signed a daily safe start, are inducted, have the relevant permit for their works, receive weekly tool box talks and are working to the appropriate risk assessments and method statements.Ensure the works are planned out in a logical manner paying particular attention to materials storage, deliveries, plant and traffic movements, craneage and any other site logisticsManagement of plant to ensure it is ordered in advance, used efficiently, tracked while on site and off-hired when no longer requiredManage labour resources and ensure these do not exceed the labour forecast for the projectEnsure all materials are taken off, ordered and delivered to site in advance of any works and in line with the construction programmeEnsure all managers/engineers and sub-contractors are working to the latest construction issue informationLiaise with the senior engineer on site to ensure that all setting out is done in good time and its accuracy is checkedEnsure all the relevant QA is completed by the engineers, as well as any sub-contractors working under you. Report to the PM any items raised with regards to QA and propose remedial actionsHold weekly (as a minimum) progress meetings with the site team and subcontractors and report to the project manager on progress of works against programme Competencies: Excellent computer skillsGood attention to detailAbility to read and communicate drawingsHardworking and driven to push projects throughAbility to meet deadlines: delivers projects on timeWorking closely with a team About Ardmore: We are one of the largest family-owned construction groups in the UK. Multi phase regeneration schemes with dense urban housing to high-rise developments, luxury residential projects and bespoke hotels are a few examples of our work.There are few companies in today's construction industry that can provide the same level of in-house capability as Ardmore including in-house mechanical and electrical installation, as well as metalwork and joinery services.Groundwork and substructures, super-structures, mechanical and electrical installation, through to envelope and fit-out packages we are able to control and deploy our own staff, equipment and tradespeople efficiently,whilst also providing clients with flexibility and responsiveness. Unsolicited CVs: in relation to speculative CVs received from providers without a prior assignment issued in writing by Ardmore's Recruitment team, no fee payable by Ardmore will apply.


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|Home | About | Journals | Submit | Contact Us | Français
To investigate the pathogenicity of T cells infiltrating in the rheumatoid joints, mononuclear cells (MNC), predominantly T cells, isolated from either synovial fluid or synovial tissues of the patients with RA were transferred into severe combined immunodeficient (SCID) mice by intraarticular injections. According to our observations in this experimental system, patients with RA could be classified into at least two groups. In one group of patients, the infiltrating MNC induced synovial hyperplasia in the recipient SCID mice (the positive group). Whereas, in the other group no synovial hyperplasia was observed (the negative group). The induction of synovial hyperplasia observed in the positive group was prevented by an anti-human CD3 antibody (OKT3), indicating T cell mediation. Analysis of T cell receptor (TCR) V beta usage by reverse transcriptase polymerase chain reaction in the infiltrating MNC transferred into SCID mice revealed a marked skew towards the preferential use of certain V beta genes, which was not seen in the peripheral blood MNC, in only the positive group. The patterns of TCR/V beta skew were not uniform among the patients. The analysis of the PCR-amplified genes of such skewed TCR/ V beta by single strand conformational polymorphism showed distinct bands, indicating that the T cell populations expanding in rheumatoid joints of the positive group were oligoclonal. Furthermore, the enrichment of the T cell populations expressing such skewed TCR/V beta by in vitro stimulation of peripheral blood MNC of the patients with the relevant superantigen enabled the induction of synovial hyperplasia in the SCID mice. These results suggest that the pathogenic T cells could be activated locally in rheumatoid joints by certain antigens in some, but not in all patients with RA.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


text:
3 Responses to "wedding-invitation-templates_2"
We request the pleasure of your company on the auspicious occasion of our wedding.
Your presence will add on to our Happiness !
So do come and give us the chance to rejoice the occasion with your company …
Venue: Mini Kailash Nahal, No: 42B, Mounasamy Madam Street, Ambattur, Chennai – 600053.
Date : September 1 2013, Sunday
Muhurtham : 07.00 A.M to 08.30 A.M
Aishwarya and Vinoth Kumar
The comment above was posted by mistake thinking its getting printed on the card. But am unaware that this is a comment box. If anyone could help me in deleting this. Please reply


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Yamaha Tyros5 76 Note Arranger Keyboard
Yamaha Tyros5 76 Note Arranger KeyboardDetails
The Yamaha Tyros5 76 Note Keyboard offers every feature needed for the arranging or studio musician. The Tyros5 is equipped with over 1000 sampled instruments with authentic tones and dynamic responses. The included effects are created through VCM circuits for a more detailed response to your notes. This model has 76 keys, each with an adjustable touch response to suit your exact preference. The LCD display is a useful interface for navigating through the Tyros5's features. The Tyros5's recording function is ideal for the advanced musician wanting to create pieces directly to WAV. The Tyros5 will keep your performances and recordings inspired.
Special Offer: Any Yamaha Tyros5 model purchased will include a free Entertainer Gold Expansion Pack worth £500. This pack features a whole range of voices and tones to add to your Tyros5's library.
Product Ref: 63703View Full Description
Buy on finance from £81.90 per month Finance from £81.90 per month
Please note: This is only available where all items in the order are dispatched in a single delivery.
To make it as easy as possible for you to get the gear you want, we offer a range of instant finance options. If you spend £250 or more online, you can choose to pay over 48, 36 or 24 months. The majority of decisions are given instantly, so you could get your new gear sooner than you thought!
Representative Example
To help you understand how our finance options work, the examples below are based on a total order value of £250:
|Deposit to Pay
|Total Payable
|Classic Credit 48 Months 14.9%
|No Deposit
|48 months: £6.83
Final payment: £6.83
No settlement fee
|Classic Credit 36 Months 15.9%
|No Deposit
|36 months: £8.65
Final payment: £8.65
No settlement fee
|Classic Credit 24 Months 18.9%
|No Deposit
|24 months: £12.41
Final payment: £12.41
No settlement fee
How to Apply
Applying for finance couldn't be easier - if your order totals £250 or more, simply proceed through the checkout as normal, then select Pay by Finance on the payment page, then click the orange APPLY FOR INSTANT FINANCE button. This will start your application with V12 Retail Finance, our finance partner, and completing this form should take approximately 10 minutes.
You should get an instant answer on whether your application has been successful, though in some rare cases V12 may need to look at the application in more detail.
Please note: This is only available on orders placed via the website consisting of a single delivery, and is not available in store or via phone currently.
Full DescriptionView Full Description
Free Gold Entertainer Package
Customers will receive voucher codes to download two exciting new Expansion Packs, "Entertainer 2016" and "Euro Dance 2016".The Expansion Packs offer a total of 140 additional styles, 80 Voices, 22 MultiPads and 27 Registration Banks, which are perfect for Tyros5 players performing genres such as Entertainer, Schlager, Volksmusik, Ballroom, Swing, Pop, Rock, Disco, Dance and House. More than 50 of the styles are completely brand new and have been specially created for performing up-to-date hits and classic favourites. The two free expansion pack downloads are available from the Yamaha MusicSoft online store. Your Tyros will include a step-by-step download and installation guide.
Sounds and Effects
With a total of 1279 voices available, the Tyros5 can fit the requirements of the most discerning musician. Each voice's notes are sampled from four players for a dynamic, authentic sound. When multiple notes are played, the Tyros5 projects only the most important sounds from each instrument to avoid excessive stacking. Each musical instrument has its own section for edits and enhancements of the parameters, which is ideal for achieving your exact tonal preference. The voices include extensive ranges for brass, guitars, synths, orchestral and more. Each instrument is realistic and suitable for the professional studio setting.
Virtual Circuit Modelling
All of the Tyros5's effects have been made using the advanced VCM technology. This technology focuses on recreating the warmth and consistency of analog circuits, but in a modelling format. The VCM offers precise controls that can create as subtle or heavy a control as required. The Real Reverb has updated and more dense technology for a more natural decay. The Real Distortion focuses on copying the classic sounds of amplifiers and effects pedals and recreating them in a digital format. Many of the distortion modes are focused on capturing the sound of the 1960s and 1970s. The VCMs can all be edited from the Tyros5's interface and feature realistic control layouts for the most user-friendly experience.
Central Interface
The digital interface is a useful hub for navigating across the Tyros5's features. The screen is in full colour for the most bright, engaging and helpful look possible. The controls are labelled to the side of the screen for easy accessibility. The screen has an adjustable tilt for use on stages, whilst its large size offers a clear readability. The other controls labelled across the Tyros5's board offer instant access to a number of the features including the recording, voices and styles. To the left of the keyboard are the pitch bend and modulation wheels for producing the classic, spontaneous effects to your performance.
Record and Playback Audio
The updated recording functions on the Tyros5 are an ideal tool for a variety of uses. For developing musicians wanting to listen back to their pieces as a way to improve, its quick playback is ideal. Arranging musicians will also be able to use the recording function to stack different sections of a piece with separate instruments. For songwriters wanting to record everything directly from one system, the included microphone connection and level balancing allows you to record everything to WAV files for optimum convenience. USB connectivity has seamless linking to your computer for the easiest recording experience possible.
- Width: 1347mm
- Height: 142mm
- Depth: 450mm
- Weight: 16KG
- Number of Keys: 76
- Key Type: Organ FSX
- Touch Response: Hard 1, Hard 2, Medium, Soft 1, Soft 2
- Tone Wheels: 2
- Sliders: 9, Cross Fader
- Sound Profile: AWM Stereo Sampling
- Maximum Polyphony: 128
- Number of Voices: 1279
- Number of XG Voices: 480
- Drum/SFX Kits: 37
- Compatibility: XG, GS, GM, GM2
- Voice Styles
- Ensemble: 55
- S.Art: 288
- S.Art2: 44
- MegaVoice: 54
- Live: 138
- Cool: 81
- Sweet: 37
- Organ World: 40
- Reverb: 52 Presets, 3 User
- Chorus: 106 Presets, 3 User
- DSP1: 322 Presets, 3 User
- DSP2-9: 322 Presets, 10 User
- Master Compressor: 5 Presets, 5 User
- Master EQ: 5 Presets, 2 User
- Vocal Harmony Presets: 44
- Synth Vocoder Presets: 10
- User Settings: 60
- Vocal Effect: 23
Audio Recorder/Player
- Recording Time: 80 Minutes
- Recording Format: WAV Format, 44.1 kHz Sample Rate, 16-Bit Resolution, Stereo
- Playback: WAV, MP3
- Time Stretch: Yes
- Pitch Shift: Yes
- Vocal Cancel: Yes
- Headphones: Yes
- Foot Pedal: Sustain, Articulation, Volume, Function Assignable
- Microphone: Combo Jack
- MIDI: 2 x In, 2 x Out
- Aux In: L/L+R, R
- Line Out: Main (L/L+R, R), Sub Out (1,2), Aux Out (3,4)
- RGB Out: 1
- USB to Device: 2
- USB to Host: 1
The product price includes 2 years' warranty and 30 day money back guarantee.
However, the Gear4music extended warranty scheme provides an enhanced service, and is designed to offer a higher level of protection than many 'free' warranties offered by some retailers and manufacturers.
The highlights of this enhanced warranty service are:
- Warranty is extended to 6 years from the date of delivery.
- Our Money Back guarantee is extended from 30 days to 180 days (terms apply after 30 days)
- Collection and delivery costs are included for the first 2 years
- Claim 50% cash back on the cost of the policy after 6 years if it has not been used!
- Warranty is transferable if the item is re-sold
- Loan or replacement equipment will be provided if the product isn't repaired within 30 days
- If an item can not be repaired, a similar alternative product or cash discount (as defined in this policy) will be offered
- The policy can be cancelled within 30 days, and at any time after that for a pro-rata discount
Please note that this extended warranty is currently only available on products sold within the EU or EEA, and is subject to the terms and conditions as detailed on the extended warranty certificate provided.
For customers in outlying areas of the country, the price of the Extended Warranty may be marginally higher, due to the potential for higher collection and redelivery transport costs.
This enhanced warranty is in addition to the standard Gear4music and manufacturer warranty policies, and the Gear4music terms and conditions of trade. No statement or condition of sale contained within these terms affects or restricts your statutory rights as defined under the Consumer Contracts Regulation 2014.
Once the product is delivered, you have 30 days to decide that you definitely want to keep it. If you decide it is not suitable for any reason, you can return it back to us for replacement or full refund, including standard delivery charges.
All Products are new unless stated, and include a minimum of 2 years warranty.
Some items are only eligible for money back guarantee if they are returned to us unused and sealed in the original packaging, and in the case of software, unregistered. These items include:
- Software
- CDs & DVDs
- In-ear Monitors
- Earplugs and Ear Protection
- Mouthpieces, Reeds etc… for Woodwind and Brass instruments
- Mouth / Lip Care Products
We are unable to accept returns of any custom made items designed to work together as a unique package, such as computer system built to a customer's personal specifications. Exceptions may only be possible with prior agreement of the vendor, and may be subject to a cancellation fee.
If you also purchase items that do not qualify for free delivery, some delivery charges may be applied to your order which will be shown in your shopping basket.