text:
|Número de publicación
|Tipo de publicación
|Número de solicitud
|Fecha de publicación
|15 Jun 1993
|Fecha de presentación
|20 Dic 1991
|Fecha de prioridad
|20 Dic 1991
|También publicado como
|Número de publicación
|George C. Tibbetts, Peter L. Madaffari
|Cesionario original
|Tibbetts Industries, Inc.
|Exportar cita
|BiBTeX, EndNote, RefMan
|Citas de patentes (2), Citada por (72), Clasificaciones (14), Eventos legales (5)
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet
This invention relates generally to electroacoustic transducers intended to be worn in the ear of the user, where the excretions that occur in the ear tend to enter any orifice or outlet passage that is utilized to introduce sound into the user's ear canal. In many prior art hearing aids incorporating such transducers, build-up of these excretions, referred to as ear wax or cerumen, ultimately blocks all or part of the sound outlet passage, causing a malfunction of the hearing aid.
U.S. Pat. No. 4,800,982 issued Jan. 31, 1989 to Elmer V. Carlson discloses a hearing aid having a cleaning passage, a part of which comprises the sound outlet passage. Cleansing is effected by pumping a solvent through the cleaning passage. Numerous other U.S. patents have issued on a variety of wax or cerumen traps or guards, so-called, and many such traps are in use in commercial in-the ear hearing aids, including in-the-canal aids. Such traps are only partially effective. In the worst case, extended use without adequate cleaning results in irreversible plugging of the acoustic outlet of the output transducer within the hearing aid, and in complete failure of the hearing aid in use. In the best case, the particular trap plugs quite rapidly, and the performance of the hearing aid degrades until cleaning or trap replacement is repeated, the result being variable performance over its life.
Such wax plugging is reputed within the hearing aid industry to be the primary cause of field failure of in-the-ear and canal aids, associated with high rates of return to the manufacturer even within the first year of use.
Similar wax plugging problems are found in other industries which employ miniature electroacoustic transducers within or adjacent the ear canal. An example is the light weight telephone headset industry.
An object of this invention is to limit the effect of accretion of cerumen on acoustically active surfaces, and specifically to provide structures that prevent cerumen from plugging passages for acoustical energy to the tympanic membrane.
Another object is to enable the cleaning of cerumen from the transducer by the wearer without damage to its working parts.
With the foregoing and other related objects in view, the present invention provides a transducer in which the outward face of the acoustic diaphragm is placed directly within the ear canal, and there are, preferably, no intermediate passageways that can be plugged. Cerumen that becomes deposited on the diaphragm is cleanable therefrom, by the end user, by means of a brush or other suitable tool. In order to withstand such relatively rough and uncontrolled handling at its exposed diaphragm face, the transducer must have unprecedented ruggedness against such handling, while at the same time possessing the high acoustic compliance (commensurate with the acoustic compliance of its internal air cavities) necessary for efficient transduction between electrical and acoustic signals.
These requirements are satisfied by providing a transducer casing which extends along the ear canal and is at least partially sealed thereto, an atmospheric pressure vent at its outer end remote from sources of ear excretions, and an acoustic diaphragm of particular structure which completely or substantially closes a face or surface of the casing near its inner end, toward the tympanic membrane. The acoustic diaphragm is attached to an electromechanical motor unit within the casing which may have electrical terminals on or extending through the casing. The acoustic diaphragm has a central portion which vibrates substantially as a piston, at least at lower signal frequencies, and also has a film surround which seals to the casing or an adjacent structure sealed to the casing. Preferably the film of the surround provides the entire exposed surface of the diaphragm and is sealed near its periphery between a wall of the casing and a supporting structure within the casing. The surround is formed to conserve substantially the very high mechanical compliance of the diaphragm surround under substantial vibration excursions, as is conventional in many electroacoustic transducers. The film is formed inwardly toward the interior of the casing to provide elastic stability and strength to the surround under the external pressure of end-user cleaning operations.
Because of the very small diaphragm area available transverse to the ear canal, the mechanical compliance of the electromechanical motor unit itself must also be very high, to provide the required acoustic compliance of the overall transducer. The forces generated by the physical pressure of end-user cleaning, when applied to a structure having such a high mechanical compliance would cause very large deflections of the diaphragm, resulting in tearing of the surround or destruction of the motor unit. To prevent such undue deflections, a mechanical stop is provided to the diaphragm but does not affect the operation during normal signal vibrations of the diaphragm. In some structures, the mechanical stop function ma be provided by the electromechanical motor unit itself.
In one type of hearing aid incorporating transducers of the present invention, the diaphragm of the transducer may be substantially flush mounted with the inner end of the hearing aid toward the tympanic membrane of the ear. The manufacturer may provide a temporary cap for the transducer to protect it during storage or handling of the hearing aid when not in use. He may alternatively provide a perforated cap to protect the transducer during use, or to modify its frequency response. If so, the cap must be at least partially removable for cleaning or replacement.
The transducers of this invention may also be used to construct a new type of deep insertion canal aid. In these structures the casing of the transducer extends well beyond the inner end of the nominal shell of the hearing aid, deeper into the ear canal, and has its own seal to the ear canal, near the diaphragm end of the transducer.
FIG. 1 is a composite view of a first embodiment of a transducer according to the invention.
FIG. 2 is a detail elevation in diametric section of the diaphragm means of the first embodiment.
FIG. 3 is a complete elevation in longitudinal diametric section of the first embodiment, having an intrinsic form of mechanical stop means.
FIG. 4 is a partial elevation in diametric section showing an alternative form of mechanical stop means.
FIG. 5 is a composite view of an in-the-ear hearing aid incorporating said first embodiment.
FIG. 6 is a composite view and elevation in section of a hearing aid similar to that of FIG. 5.
FIG. 7 is an isometric view of a second embodiment of a transducer according to the invention.
FIG. 8 is a composite view and elevation in section of a deep insertion canal aid incorporating said second embodiment.
FIG. 1 shows a complete transducer according to the present invention. In this invention, a casing member has a wall of hollow tubular shape. In FIG. 1 it is substantially cylindrical and of circular cross section, and comprises a flanged tube 1 which is substantially closed at one end by a flanged terminal cup 2. The wall of the tube 1 forms a circular rim at its end opposite the cup 2. The flanges are welded together, the welds extending through an optional structural part 16 fixed between the flanges, hereinafter described in connection with FIG. 3. The cup 2 carries a terminal board 3, which has electrical terminal pads 4 and 5. An atmospheric vent 6 passes through an aperture in the cup 2 and is adhesive bonded thereto. A diaphragm assembly 7 closes the opposite end of the tube 1 and is sealed to it by adhesive. The diaphragm assembly 7 has a central portion 8 which is provided by a substantially circular diaphragm reinforcement 9 with its peripheral edge spaced from the wall of the casing. The reinforcement 9 is a hot extrusion or forging of age hardenable high strength aluminum alloy, and has an integral stem 10. High strength, thin flexible polymer film, typically a 1.5 to 2.5 micron thick biaxially oriented polyethyleneterephthalate film, covers the central portion 8 and is hot adhesive bonded to the reinforcement 9. The film extends into a free diaphragm surround 11 which is arched inwardly by hot forming, and may have approximately the shape of a portion of a torus. Beyond the surround 11 the film is hot formed and adhesive bonded to a ring-like diaphragm frame 12, which is shown in FIG. 3. The outer peripheral area of the film is trapped between the inner wall of the tube 1 and the adjacent outer wall of the frame 12. The outer surface of the central portion 8 of the diaphragm assembly is substantially coplanar with the rim of the tube 1.
There is no passageway through the diaphragm assembly 7, since this would be subject to plugging by cerumen. Instead, the necessary equalization of static pressure on each side of the diaphragm assembly is provided by the atmospheric vent 6.
When the transducer of FIG. 1 is in place within the ear of the user, a space is defined which is generally bounded by the ear canal, the tympanic membrane and the diaphragm assembly 7.
Referring to FIGS. 1 and 3 a particular electromechanical motor unit 13 is supported within the casing of the transducer. The motor unit 13 is preferably of the kind described in the copending application of George C. Tibbetts filed on even date herewith and entitled, "Balanced Armature Transducers with Transverse Gap." The motor unit 13 has a vibrating armature 13a connected to the stem 10 of the diaphragm assembly 7, and has internal electrical leads 14 and 15 extending to and soldered to the pads 4 and 5 respectively. The structural part fixed between the flanges of the tube 1 and cup 2 is the peripheral rim of a restoring spring 16 (FIGS. 1 and 3) of the motor unit 13. The restoring spring is preferably adapted to stabilize the armature against magnetic snap over, and has a hub attached to a pin 13b which is attached to both the armature 13a and the stem 10. The spring 16 has spokes extending from the hub to the peripheral rim. The rim and hub are substantially coplanar, but the spokes are formed along the longitudinal axis of the transducer to provide a sufficient degree of linearity to the force-deflection characteristic of the spring 16.
FIG. 3 details the mounting of the diaphragm assembly 7 in the tube 1. The formed skirt of the film that forms the diaphragm surround 11 and also covers the central portion 8, is trapped between the adjacent walls of the diaphragm frame 12 and the tube 1, and is adhesive bonded to both walls. In this way the surround 11 is very strongly attached against external pressure such as that due to end-user cleaning.
FIG. 2 is a plane section of the diaphragm assembly 7, with the film of the surround 11 exaggerated in thickness. Protection must be provided against excessive deflection of diaphragm reinforcement 9. In FIG. 2, for example, the desired limit on the upward deflection of the central portion 8 is illustrated by a broken line 17, and the desired limit on the downward deflection of the stem 10 is illustrated by a broken line 18. The causes of excessive deflection include, as in typical prior art transducers, acoustic shock and mechanical shock which can cause either direction of motion. For example, the peak shock load resulting from the dropping of a hearing aid can exceed several thousand G.
As in some prior art transducers, this invention contemplates that a mechanical stop function protecting against such specific causes may be provided by the electromechanical motor unit itself.
However, in the case of the present invention there is a third cause of excessive deflection, specifically deflection toward the line 18. This cause is external positive pressure applied by the user when cleaning cerumen from the outer face of the diaphragm assembly. This imposes an additional, severe requirement upon the means providing the mechanical stop function. According to this invention, this additional requirement may also be met by the electromechanical motor unit itself; or it may be met by additional mechanical stop means incorporated in the transducer structure. Structures of both forms are hereinafter described, and in either case the transducers of this invention are characterized by superior mechanical shock resistance as compared with typical prior art transducers.
With the diaphragm reinforcement 9 protected against excessive deflection, the free diaphragm surround 11 itself must withstand the external pressure due to end-user cleaning, particularly such pressure that tends to be localized where the surround 11 is not attached or supported. As shown in FIGS. 2 and 3, the surround 11 is well adapted to do this. It is strongly attached, its radial extent is relatively small, it is arched inward to avoid buckling under positive external pressure, and the arch is of high curvature to reduce the membrane stresses induced in the film of the surround during end-user cleaning.
FIG. 3 illustrates a structure in which the electromechanical motor unit 13 itself provides the necessary mechanical stop function for the diaphragm means. As described in said copending application, the motor unit includes a pair of permanent magnets 13c which establish polarizing flux acting in association with signal currents in coils 13d to vibrate the armature 13a in the axial direction of the pin 13b. The magnets 13c, or pole pieces attached to them, face the armature across working gaps as shown. By acting as mechanical abutments to the fully displaced armature, the magnets or their pole pieces establish the limits of motion of the diaphragm means corresponding to the lines 17 and 18 in FIG. 2.
In cases where the electromechanical motor unit itself does not sufficiently limit the inward deflection of the diaphragm reinforcement 9, or tends to do so but is not strong enough under end-user cleaning, a mechanical stop is provided. FIG. 4 shows such a stop at 19. The stop 19 is a generally cone shaped washer formed to give it good self-strength, and typically it rests on another structural member, such as a sleeve 20, which is strongly attached within the tube 1. Alternatively the stop 19 may be laser welded in place through the wall of the tube 1. The stop 19 may have one or more perforations 19a to provide an acoustic passage or passages as the gap between diaphragm reinforcement 9 and the stop 19 approaches zero during electroacoustic operation of the transducer.
FIG. 5 shows an application of a transducer 21, such as the transducer of FIG. 1, to a canal aid 22 having an inner end of its shell at 23. The inner end 23 faces toward the tympanic membrane when the canal aid 22 is inserted in the ear of the user. The transducer 21 is mounted within the canal aid 22, such that the central portion 8 of the diaphragm is substantially flush with the inner end 23. A temporary protective cap, not shown, may be provided. Cerumen accumulation on the exposed face of the diaphragm, including the diaphragm surround 11, will affect the shape of the frequency response of the transducer 21, and secondarily its sensitivity, but this contamination may be cleaned readily from the diaphragm by the end-user. Indeed, if the tube 1 of the transducer 21 is tightly sealed to the shell of the canal aid 22 at its inner end 23, detergent solutions used locally and followed by thorough rinsing and drying can be used to accelerate cleaning.
FIG. 6 shows a similar substantially flush mounted application of the transducer 21 to a canal aid 24 having its shell bonded to a face plate 25. The face plate contains a volume control 26, an electret microphone 27, and a battery compartment 28 hinged at 29 and containing a single cell battery 30. A semiconductor amplifier 31 is bracketed to the face plate 25. Thin wall silicone rubber tubing 32 is shrunk over the casing of the transducer 21, and seals it at 33a to the end wall 33b of the shell of the canal aid 24. Silicone sealant may also be applied at 33a.
Clamps, schematically indicated at 34, grip the tubing 32 where it forms over the flanges of the tube 1 and cup 2, and resiliently clamp the transducer 21 to the shell of the canal aid 24. The silicone rubber tubing 32 provides some vibration isolation . between the transducer 21 and the shell of the canal aid 24. Flexible external electrical leads 35 and 36 are soldered to pads 4 and 5 respectively, and connect to the amplifier 31. Other electrical connections within the canal aid 24 are conventional and for clarity are not shown. The atmospheric vent 6 preferably is fabricated from small polytetrafluoroethylene sheathed stranded wire, the sheath of which has been etched to allow adhesive bonding to the terminal cup 2. The use of this polymer sheathing permits the proximate soldering of the leads 35 and 36, and provides flexibility to the vent 6, while the stranded wire core provides a reasonably controlled flow resistance to the atmospheric vent 6. Ordinarily the canal aid 24 is not gas tight, and therefore the ambient atmospheric pressure is communicated to the vent 6. After the leads 35 and 36 are soldered, and most of the operations that might plug the atmospheric vent 6 are finished, but before the face plate 25 is bonded to the shell of the canal aid 24, the vent is shortened and provided with a fresh outer end by snipping it to the desired length.
An additional, acoustically active vent 37 may bypass the transducer 21 and extend through the face plate 25 and the end wall 33b.
Such vent means is commonly used to relieve excess static pressure in the ear canal, to ventilate the ear canal somewhat, and to modify the overall frequency response of the particular hearing aid, such as canal aid 24.
The transducers of the present invention need not have a casing of substantially cylindrical shape, and the casing need not have flanges, but such transducers may have a casing of any shape that is useful within the ear canal or within a device to be inserted in the ear canal. However, because of the general shape of the human ear canal, a transducer casing of substantially cylindrical shape which has an oval cross section is particularly useful in these end applications, and is relatively straightforward to manufacture. FIG. 7 shows an isometric view of a transducer having such a casing. The rim of the casing lies substantially in a plane and its outline comprises substantially a pair of semicircles smoothly connected by parallel lines. Flanges are shown, although other means may be employed to close or complete the casing at its terminal end.
Thus FIG. 7 shows a transducer 40 cased by a flanged tube 41 and flanged cup 42, both of oval cross section. An atmospheric vent 43 extends through the end wall of the cup 42. A diaphragm assembly 44 has an oval central portion 45 defined by a diaphragm reinforcement which, as in the embodiments of FIGS. 1 to 4, attaches internally to an electromechanical motor unit within the casing of the transducer 40. Thin film covers the central portion 45, where it is bonded to the underlying diaphragm reinforcement, and extends outward to form a concave diaphragm surround 46. Outwardly of the surround 46 the film is sealed to the interior wall of the tube 41. There is no aperture through the diaphragm assembly 44.
In FIG. 8 the transducer 40 of FIG. 7 is used to provide a new type of deep insertion canal aid 50. The nominal shell 51 of the canal aid 50 has an end wall 52 which is apertured to accept the transducer 40. Prior to the bonding of a face plate 53 to the shell 51 and prior to the attachment of a seal 56, the tube 41 of the transducer is inserted through this aperture until the flange of the tube 41 abuts the interior of the wall 52. Unlike the canal aid of FIG. 6, the flanges of the tube 41 and cup 42 are bonded to the wall 52 and an adjacent portion of the shell 51 with a substantially rigid adhesive, thus locking the transducer 40 strongly in place. Electrical lead 54 connect the respective terminals pads of the transducer 40 to an amplifier 55. Since much of the tube 41 is exposed to the environment of the ear canal, it is gold plated or otherwise coated so as to be inert and non-sensitizing to the ear canal.
With most of the tube 41 extending beyond the end wall 52, as shown in FIG. 8, the wall of the tube 41 becomes in effect a portion of the shell of the canal aid 50. The significance of this is that the tube 41 is smaller in cross section than any shell that could surround it, and the reduction in size enables the diaphragm assembly 44 to be inserted more deeply toward the tympanic membrane.
This reduces the parasitic air volume between the diaphragm assembly 44 and the tympanic membrane, and has the effect of increasing the electroacoustic sensitivity of the transducer 40. This structural combination also allows the use of an optional peripheral seal 56 which is local in extent, resulting in a more effective, and at times more comfortable, seal to the ear canal. Typically the seal 56 is a prescription molding, to fit the individual user's ear, of low durometer medical grade silicone rubber, and it extends slightly beyond the diaphragm assembly 44 and has an internal step which covers the extreme tip of the tube 41, to protect the ear canal of the user from that end of the tube 41. The seal 56 may be designed to snap off and on, or it may be bonded to the tube 41 with a suitable adhesive or sealant. The seal 56 may have a venting notch 57 to relieve excess static pressure in the ear canal. A notch of this type in the seal 56 is subject to plugging by cerumen, but is readily cleaned by the user. For the venting notch 57 to be effective, the canal aid 50 may have a bypass vent similar to the vent 37 discussed with reference to the canal aid 24 of FIG. 6. As an alternative to the seal 56 notched at 57, the seal may be fabricated from an open pore flexible foam of polymeric material such as a polyurethane. The porosity of the foam provides venting but will become plugged by cerumen accumulation. Seals of this type must be designed to be readily removed and replaced by the user.
Although the transducers illustrated in the above FIGURES are intended as output transducers, the structures of this invention are also applicable as so-called in-the-ear microphones, in which the input signal to the transducer is the acoustic pressure resulting from tissue and bone vibrations within the blocked ear canal and caused by the wearer's voice.
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|Clasificación de EE.UU.
|381/328, 381/418, 381/325, 381/23.1
|Clasificación internacional
|Clasificación cooperativa
|Clasificación europea
|20 Dic 1991
Owner name: TIBBETTS INDUSTRIES, INC., MAINE
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:TIBBETTS, GEORGE C.;MADAFFARI, PETER L.;REEL/FRAME:005965/0673
Effective date: 19911219
|15 Mar 1994
|Certificate of correction
|27 Jun 1996
|Fee payment
Year of fee payment: 4
|5 Dic 2000
|Fee payment
Year of fee payment: 8
|16 Nov 2004
|Fee payment
Year of fee payment: 12


text:
The Switzerland international was a rare bright spark for the relegated Robur last season, scoring seven goals in 17 games after his arrival in January.
But the board member has admitted that the Tuscan side probably won't keep the striker for long.
"The boy has a lot of interest," Antonelli told Sky Sport Italia. "Sampdoria are just one of a number of clubs interested.
"Innocent has had a lot of attention. We have had a lot of curiosity calls.
"I guess Sampdoria would be keen to have him.
"An approach could have been made, but not through us."
Read the original article on Football Italia - The ultimate website for English-speaking fans of Italian football
- Sports & Recreation

subset: commoncrawl


text:
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- How much is it going to cost to hire a lawyer?
- How much is it going to cost to hire a lawyer?
At Kiley Law Group, we don't charge our clients one cent prior to settling their case. Our No Win, No Fee Promise assures our clients that we will do everything possible to get them the compensation they deserve, or we don't get paid. We offer our services on a contingency fee basis, meaning you don't pay us when we sign you as a client, but when we recover money on your behalf. We also offer FREE case evaluations to help you determine what your legal options are, and are willing to come to you, whether it's at your home, place of business, or even the hospital. For more information about how the motorcycle accident team at Kiley Law Group can help you, call us NOW at (888) 208-1695.
Our Successful Motorcycle Accident Lawsuits in Massachusetts
- $785,000 for a crushed ankle injury to a motorcyclist
- $485,000 for motorcycle accident caused by a motorist failing to stop at a posted stop sign
- $270,000 for a deadly motorcycle accident caused by a senior driver's negligence
- $265,000 for motorcycle accident fracture injuries
- $160,000 for fractured right gemur in a head on collision
- $100,000 for soft tissue injuries in a motorcycle accident
- $90,000 for ankle fracture in a motorcycle accident
Attorney Tom Kiley Rides, and Knows How Dangerous Roads are for Motorcyclists
No one understands how dangerous the road is for motorcyclists better than a fellow rider. Attorney Tom Kiley has been an avid motorcycle enthusiast for the last 20 years. He understands the hazards that motorcyclists have to overcome on a daily basis, and is aware of the severity of motorcycle accident injuries.
Often times, accidents are not the fault of motorcyclists, but of other drivers who simply do not know how to properly share the road. At Kiley Law Group, our attorneys understand this, and build strong cases on behalf of all our clients. Just because other motorists might consider a motorcyclist a nuisance doesn't mean that motorcyclists don't have the same right to be safe while traveling Massachusetts roads and highways.
Kiley Law Group is a strong advocate for motorcycle safety, and is committed to protecting the rights of motorcycle accident victims. Regardless of what the cause of your accident may have been, our attorneys will thoroughly investigate the details surrounding your case, will front ALL costs associated with the investigation, and won't charge you one cent unless we obtain compensation on your behalf. For more information about how we can help, please call us toll-free at (888) 208-1695.
If you have been the victim of someone else's negligence while driving a motorcycle in the state of Massachusetts, you may be well within your rights to pursue legal action.
Motorcycle Accidents Can Lead to Catastrophic Injuries
Motorcycle accident injuries are often times very severe, may require months or even years of treatment and rehabilitative care, and even THAT might not be enough to fully recover. Injuries can very well lead to disability, which would greatly impact how you're able to lead the rest of your life. Some of the more common motorcycle injuries include:
- Traumatic Brain Injury - Wearing a helmet is ESSENTIAL for minimizing head injury. However, because motorcyclists are fully exposed during accidents, the likelihood that TBI can occur is MUCH higher than it is for motorists of passenger vehicles. Traumatic brain injury can have a seriously debilitating impact of an accident victim's life.
- Broken Bones - The protective confines of a car or other passenger vehicle are non-existent for motorcycle accidents victims. With all of a motorcyclists limbs exposed, the likelihood of sustaining broken bone injury is very high. While broken bones may heal, the impact they have on mobility can be long lasting.
- Spinal Cord Injury - Injuring the spine is a very real possibility if you've been involved in a motorcycle accident. Recovery from spinal injury can be difficult, and the victim may never be the same again. Being fully exposed to the sheer impact of another vehicle may result in severe damage to the spine, particularly permanent paralysis.
At Kiley Law Group, it's our job to hold those responsible for your accident accountable for their actions. Your injuries may heal, but they may also leave you permanently impacted because of another person's negligence. We will examine every detail surrounding your accident, will build the strongest case we possibly can using the details of your case, and will work tirelessly to ensure that you receive the compensation necessary to heal from the impact of your accident.
ORDER NOW: Do Loud Pipes Save Lives? A Biker's Guide to Accidents and Injuries
As with everything, information is power. A motorcycle accident can be a devastating moment for any family, no matter how familiar they may be with bikes. The shock can be paralyzing and leave the survivors grasping for answers.
But you are not alone and there is information at your disposal. You MUST get your hands on this FREE motorcycle accidents book. It lays out your options in plain, easy-to-understand language, and reveals insider information the insurance companies don't want you to know. Massachusetts motorcycle accident lawyer, Tom Kiley, is an avid motorcycle rider and has represented individuals against insurance companies for over 30 years.
Why Should I Hire an Attorney After My Motorcycle Accident?
While the process of pursuing a claim may seem overwhelming now, and no amount of money can undo the damage done, retaining the services of a dedicated personal injury attorney could be advantageous for a number of reasons:
- Medical Expenses - The primary reasoning behind any personal injury claim can be the mountain of medical bills that can follow in the wake of a motorcycle accident. Motorcycle injuries can take on many forms, from physical damage to emotional distress, to say nothing of the difficulties you may face in the future. All of these expenses can end up costing hundreds of thousands and, in some instances, may financially bury your family. You've already paid enough for someone else's carelessness, why let the abuse continue?
- Insurance - With medical expenses, insurance companies aren't far behind. It is common practice for agencies to aim for the lowest possible settlement when dealing with just about any motorist. Their processes can be deliberately confusing if not downright deceitful. For motorcyclists, the scrutiny can be even greater. Their underhanded tactics and dubious assertions can become incredibly complex. An experienced personal injury attorney can help clear the fog of claims adjusting and work as a representative on your behalf.
- Investigation - With decades of experience, the Kiley Law Group knows the value of a thorough investigation when it comes to motorcycle accidents. When pursing a successful claim it is critical to have as much information from the accident scene as possible. Tracking down photographs, police reports and surveillance footage are the first steps your legal team will take. Consulting with medical experts can demonstrate how your injuries were sustained and how the resultant damage has negatively impacted your life. Crash reconstruction experts can provide a clearer understanding of the events leading up to the wreck and determine who may be at fault.
Contact a Boston Motorcycle Accident Law Firm Today
After an accident, injured motorcyclists have one very important job - fully RECOVER from any and all injuries brought on by the accident. At Kiley Law Group, our legal team also has one very important task - RECOVER fully on behalf of our clients so that they can try to put the accident and all costs associated with it behind them. If you've been injured in a motorcycle accident, call our Boston personal injury attorneys NOW at (888) 208-1695. We provide all of our potential clients with a free, no-obligation consultation, we answer any and all questions thrown our way, and we front all costs associated with building your case. You have absolutely nothing to lose by calling Kiley Law Group for help with your Boston motorcycle accident case. Regardless of where you're located in Massachusetts, our legal team will come to YOU, no questions asked, no fees charged. Call us today.
Call us today for a free consultation


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20.109(S08):Student registration and questionnaire
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===Last Name===
===Last Name===
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Please copy the source code from this page to your user page, fill in the answers and print out a copy for next time.
You do not need to keep the information on your user page once you've printed it out.
Registration/Questionnaire: 20.109 Spring 2008
Last Name
First Name
Emily Jean
Preferred name
Year of Graduation
Telephone #
ejonufer AT mit DOT edu
Have you taken
7.05/5.07 (Biochemistry)
7.06 (Cell Biology)
7.02 (General Biology Lab)
5.310 (General Chemistry Lab)
In the process of taking 7.05
Do you have any experience culturing cells (mammalian, yeast or microbial)?
Do you have any experience in molecular biology (electrophoresis, PCR, etc)?
Yes, a slight amount (from high school).
Please briefly describe any previous laboratory experience
None, except high school labs (IB Chemistry and Biology).
Anything else you would like us to know?
I am excited! I know that I might not be the most experienced but I am ready to learn!


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Frosting or Icing? Firefly or "Peenie Wallie"? Brew-Thru, Beverage Barn, or "I Have Never Heard of This Concept"?
I have taken this regional dialect quiz from N.C. State University four times in the last week (the short version changes up its questions), and it has pegged me exactly every time as a person who grew up in Houston. That is crazy! Continental Americans: can it pin you down, too?
This quiz overloads if too many people are on it at once, so if you can't get to it, a perhaps even more interesting substitute is the distribution map created from the answers to each question. Did you know that, in a few coastal parts of New England, people say "Mary," "merry" and "marry" with different vowels for each word? I also had always thought all Texans said "feeder" for the access road to the highway ("freeway" for me, incidentally), but apparently it's just Southeast Texas. And it appears that in my new home of Michigan, the night before Halloween is called "devil's night"!


text: Locations Category page 11,150pages on this wiki Edit History Talk11 Sorting type: Most visited Most visited Alphabetical | This category contains entries concerning Grand Theft Auto locations. New Locations Categorizing Policy Main cities (e.g. Liberty City) should go in this category (Category:Locations) and Category:Cities All places of interest (buildings, companies, checkpoints) should go in the games category (e.g. Category:Locations in GTA San Andreas) All towns, villages and permanent or natural features should go in that main city's category Category:Vice City Try to subcategorize within these, e.g. Category:San Fierro, Category:Safehouses in GTA San Andreas etc For differing renditions of cities, simply add the game's name for every rendition: Category:Liberty City in GTA IV / Category:Liberty City in GTA III / Category:Liberty City in GTA 1 If you would like to discuss these conventions, please discuss them on the talk page Pages in category "Locations" Bone County Rancho Bohan La Puerta Elysian Island University of San Andreas, Los Santos Vice City (HD Universe) Abandoned Mine Alamo Sea Galileo Observatory Dukes Los Santos Naval Port Muscle Sands Gym Las Venturas (HD Universe) Great Chaparral Vinewood Casino Back 1 2 3 4 5 6 7 8 ... 46 Next Subcategories Towns Locations in GTA Vice City Stories Downtown Save Points in GTA San Andreas Locations by Type Cemeteries Dirt tracks Districts in Anywhere City Back 1 2 3 4 Next


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Fuel injection, developed for Ural by ElectroJet, Inc. headlines the upgrades to the 2014 Gear-Up. The closed-loop system utilizes dual ECUs that allow it to continue running if one ECU should fail. Complementing the EFI is a redesigned airbox and revised cam profiles.
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- 2 years ago by Joanna Rafael
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Pro tip: watch these movies about friends with your friends! More
Pro tip: watch these movies about friends with your friends! More
Not only have women been hilarious since the dawn on time, but anyone who watches Saturday Night Live can tell you that the ladies have been running the show for the last decade. More
On Day 5 of NYFW, we started running into our favorite famous people, including Hugh Jackman, Tina Fey, Solange Knowles, and Dita Von Teese. Amazing. More
I don't think my father, the inventor of Toaster Strudel, would be too happy to hear about this. More
If you're going to give somebody the verbal middle finger, you might as well do it in front of millions of people and everyone you've ever worked with. More
Once again the Golden Globes were hosted by Super Friends Tina Fey and Amy Poehler. Let's overanalyze everything they wore last night. More
Even though we knew that Tina Fey and Amy Poehler's 2014 Golden Globes opening would be amazing, we had no ideas that it would be this good. But that could just be the puddle of pee that I'm sitting in right now talking. And yes everyone out there who's shaking their head in disgust, peeing your pants is the kindest compliment you can pay a comedian. Followed closely by the Gchat "HAHAHAHAHAHA." More
As per usual, some people seriously sucked on the 71st Golden Globes red carpet. We're here to name names, call out peplums, and simply ask, "Why?"
Featuring: Sandra Bullock, Kerry Washington and Jennifer Lawrence (yeah, really). We're sad about this all, too. More
As always, we'll be updating as the night progresses, so check back for more gowns, weird suits, and our perplexed, off-the-cuff reactions. More
While Tina Fey and Amy Poehler haven't always had the best luck on the red carpet, they've significantly upped their game in recent years. Let's take a look at their best red carpet looks from the last year, and take bets on what they'll show up in on Sunday night. More
Jennifer Lawrence is certainly on the road to winning every Most Likable Celebrity Award ever if they existed, what with her adorable tripping, congenial dorkiness, seeming lack of a filter, and "normal" girl brand. More
Last night's Anchorman 2 premiere drew out some of our favorite people in fancy clothes, including Tina Fey, Amy Poehler, and more. More
Crying "shame" has simply gotten out of hand. More
Despite the fact that she's widely loved as an actress–and lauded as a crusader for more positive body image–there's been a hefty internet-wide backlash to Kate Winslet's recently-dropped Vogue cover. Of course, the problem has nothing to do with Winslet herself… and everything to do with Vogue's over-eager retouchers.
But the painting of Winslet on the November cover isn't exactly new territory for Vogue–they recently hacked off Claire Danes' limbs, for one. Moreover, there are quite a few covers from the last ten years that rival Winslet's for showcasing humans who don't exactly resemble humans. Let's take a look. More


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Here's Samsung's first promotional video for its new Galaxy S4 phone. It's just under four and a half minutes long, and follows the usual new-product-intro consumer video rules: The new phone is the star, there are lots of specs, and a disembodied hand taps and swipes its way through all the features.
Here's Samsung's First Ad For The Galaxy S4
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Child nutrition bill clears House Education Committee, yet raises major concerns
On May 18, 2016, the House Education and the Workforce Committee, chaired by Rep. John Kline (R-MN), approved H.R. 5003, the Improving Child Nutrition and Education Act of 2016. Introduced by Rep. Todd Rokita (R-IN), the legislation reauthorizes and reforms federal child nutrition programs. The bill passed the committee by a partisan vote of 20 to 14. The bill would reauthorize the federal child nutrition programs, including the Child and Adult Food Care Food Program (CACFP) At-Risk Afterschool Meals program and the Summer Food Service Program; however, many of the proposed changes could result in children no longer being able to access the nutritious meals they need to learn and be healthy.
Among the general provisions in the bill of major concern to afterschool and child nutrition advocates:
- Failing to address shortfalls in the summer food program (especially from an out-of-school time perspective). The streamlining provision in the bill does not allow nonprofit organizations and local government agencies (that are not schools) to operate the Summer Food Service Program year-round. Instead, sponsors receive the lower CACFP reimbursement rate, and fewer sites are eligible in order to qualify for streamlining. Rather than making it easier for providers to offer meals seamlessly throughout the calendar year, the proposed provision would result in fewer programs offering meals to children in need due to the limited eligibility and lower reimbursement rate.
- Significantly weakening the community eligibility provision (CEP). Community eligibility is a federal option in its second year of nationwide implementation that reduces administrative work and increases school lunch and breakfast access in high-poverty schools. The bill proposes to substantially reduce the number of high-poverty schools that are eligible to implement community eligibility, which would impact approximately 7,000 of the 18,000 schools currently participating in the program. 11,000 additional schools not currently participating would lose the option to implement community eligibility in future years.
- Increasing verification requirements. The bill dramatically increases school meal application verification requirements in ways that inevitably would cause eligible students to lose access to free or reduced-price school meals. Under the proposal, the number of household applications to be verified would increase significantly for many school districts, creating paperwork burdens for schools and families. A disproportionate number of vulnerable families, such as those who are homeless, migrant, immigrant or have limited English proficiency, would fall through the cracks in the process and lose access to school meals even though they are eligible.
- Block granting school meals. The legislation also includes a three state school meal block grant demonstration pilot to replace the School Breakfast, National School Lunch, Special Milk, and Team Nutrition programs. The funding would be capped and cannot exceed the amount a state received for the programs and administrative funding in fiscal year 2016. The funding for school breakfast and lunch is limited to the free and reduced-price reimbursements (eliminating about 29 cents per meal provided for other children) and takes away the additional six cents per lunch provided to schools in the Healthy Hunger Free Kids Act of 2010 for meeting the new federal nutrition standards. The states would have broad discretion to: determine which children are eligible for free or reduced-price meals and how they are determined eligible; decide the time of year that meals are provided; and abandon the current nutrition standards (meals are only required to be "healthy").
learn more about: Advocacy Budget Congress Nutrition
You took the Challenge, and Congress listened!
By Robert Abare
|Executive Director of the Afterschool Alliance Jodi Grant and After-School All-Stars D.C. participant Kyle Brewer present Rep. Bobby Scott (D, VA-03) with an "Afterschool Hero" cape to honor his heroic support of afterschool in Congress. Photo by Herman Farrer.
On Monday, May 23, and Tuesday, May 24, the 15th annual Afterschool for All Challenge brought more than 150 afterschool advocates from across the country to Washington, D.C. for two days of learning, advocating, and celebrating out-of-school time programs. Thanks to the collaboration and enthusiasm of these participants—supported by messages to Congress sent from advocates nationwide—this year's Challenge was a huge success!
Here are the amazing accomplishments of this year's Challenge:
- More than 150 participants from 36 states, including Alaska and Hawaii.
- More than 160 visits to Congressional offices on Capitol Hill, many of which were attended by Members of Congress.
- Workshops on the latest in afterschool, including child nutrition reauthorization, advocacy during election season, and afterschool in rural America.
- A panel discussion and Q&A with staffers of Members of Congress who played a key role in supporting afterschool programs in the nation's new education law, the Every Student Succeeds Act (ESSA).
- An Afterschool Showcase on Capitol Hill, featuring performances and demonstrations by local and national afterschool programs, and remarks by Senators and Representatives who championed out-of-school time programs in Congress.
- Nearly 800 messages sent to Congress by participants of the Virtual Afterschool for All Challenge.
learn more about: 21st CCLC Advocacy Congress Events and Briefings
Weekly Media Roundup: May 25, 2016
By Luci Manning
To Bridge the Gap (Arkansas Democrat-Gazette, Arkansas)
Joyce Willis, educational programs manager for the Clinton Foundation, makes the case for summer learning programs in the Arkansas Democrat Gazette: "Summer learning loss, also known as the 'summer slide,' affects nearly every student in the country…. This education loss is even more severe for students from low-income families who fall nearly three months behind in the summer…. That's why it's important for communities to come together and create opportunities for our students—all our students—to have access to quality educational and literacy programs."
Organizers: Program for Inner-City Kids is Difference Between Life and Death (WHO, Iowa)
A ten-week summer program is attempting to transform Des Moines' poorest neighborhoods into safe places for kids. "Doing More in the Core" is providing grants to non-profits and community organizations that offer activities for young people from 6 p.m. to 9 p.m. throughout the summer, a time when police say youths are most likely to get into trouble. "Everybody's home situation isn't the best," Oakridge Neighborhood site coordinator Stephen Williams told WHO. "Giving them an opportunity or a place to go or services that they can benefit from or learn from may help save a life."
"There's a Lot of Devastation," After-School Programs Brace for Budget Cuts (KFOR, Oklahoma)
Oklahoma City Public Schools' looming budget cuts will start affecting students this week as summer programs try to handle the cutbacks. Struggling students will lose out on tutoring, fun activities and meals thanks to the $30 million in planned reductions. "So, the kids will be home alone, a lot of them or out getting in trouble," Boys & Girls Clubs CEO Jane Sutter told KFOR. "It's a very economically challenged area of our community. There are not a lot of options for those kids. So, not only will they not get a nutritious meal probably during the day, they won't have positive activities to help them grow and learn… It is really time for our state leadership, our community leadership, everybody to make kids come first."
Shaking up Fitness (Austin American-Statesman, Texas)
Middle school students throughout Austin are learning that biking and running are more than just ways to stay fit – they're a way to build confidence, make friends and, most importantly, have fun. Boneshaker Project runs youth exercise programs at recreation centers and schools throughout the city, fulfilling its mission to foster a lifestyle of activity and movement. The nonprofit targets middle school kids, according to founder Todd Reed, because it's an underserved age group when it comes to these sorts of programs. "We all realize there are more resources available to elementary kids than middle school kids," he told the Austin American-Statesman. "There's a gap there, at a time when kids are very impressionable."
learn more about: Advocacy Health and Wellness Sustainability Academic Enrichment Literacy
An insider's guide to funding afterschool: Connecting donors to your mission
By Ed Spitzberg
The Afterschool Alliance is pleased to present the second installment of "An insider's guide to funding afterschool," a new blog series by Ed Spitzberg, Vice President of Development at the Afterschool Alliance, featuring strategies to successfully fund and sustain out-of-school time programs.
So now that you've leveraged the resources you have (see last month's post), let's talk about how to link donors to your organization.
What's the best way to connect donors to your organization? Well, personal relationships are important, sure. But you want long-term gifts… gifts that are tied to the organization, not any one individual. You want donors to have a relationship with the organization.
And what makes a relationship between a donor and your organization? Many things of course, but most important (and most obvious if you've peeked at the title of this post) is connection to your organization's mission.
So, how do you make this connection?
- Stories about impact – Share with donors about specific kids (without identifying information, of course) who have benefited from your program. How did they participate in your program? What changes did they have in their lives after participating in your program?
- Chance to observe program – Even better than stories: have them see your work, meet your kids and understand firsthand the impact you make.
- Chance to participate in program – And even better than observing is participating. They can volunteer to be a mentor, serve on the board or enroll their own children.
- Persistently friendly communication – Make sure they know the work you do throughout the year. Call, send e-mails, etc. Persistence is good. Annoyance isn't, so make sure you have a good feel as to where to draw the line.
learn more about: Sustainability Community Partners
Ensure your organization complies with new labor rules
Last Wednesday, May 18, the Labor Department issued a new final rule that may have implications for your program and program staff. The Afterschool Alliance will be sharing links to the latest webinars, briefings and guidelines for the new ruling as they appear. Whether or not your organization is subject to these changes will depend on your state laws.
What are the changes?
New overtime rule
The Department of Labor has announced a final rule that will substantially increase the minimum salary requirement for certain employees to be considered exempt from overtime. The new rule takes effect December 1, 2016, and is expected to extend overtime protections to 4.2 million more workers. To comply, employers may either need to raise exempt employees' salaries or reclassify affected employees as non-exempt and pay overtime when applicable.
The Fair Labor Standards Act (FLSA) requires virtually all employers to pay most employees at least the federal minimum wage for each hour worked, as well as overtime pay for all hours worked in excess of 40 hours in a workweek. The FLSA allows for exemptions from these overtime and minimum wage requirements for certain "exempt" employees. To be considered exempt, these employees must generally satisfy specific salary and duties requirements:
- Meet the minimum salary requirement;
- With very limited exceptions, the employer must pay the employee their full salary in any week they perform work, regardless of the quality or quantity of the work; and
- The employee's primary duties must meet certain criteria.
learn more about: Sustainability
Amplify afterschool voices on Capitol Hill
By Robert Abare
|Participants from 2014's Afterschool for All Challenge meet with Senate Minority Leader Harry Reid of Nevada.
Next Tuesday, May 24, more than 150 afterschool advocates from across the country will descend on Capitol Hill for the 2016 Afterschool for All Challenge. This year's Challenge participants will build support for afterschool among national legislators at a critical time, as Congress prepares to determine funding levels for the only federal funding source for afterschool programs, the 21st Century Community Learning Centers inititative.
Here's what we have planned for this year's Challenge:
- More than 150 participants from 37 states
- Hundreds of meetings with Congressional offices
- A number of insightful workshops on the latest in afterschool, including:
- Child nutrition reauthorization
- Afterschool advocacy during election season
- Afterschool in rural America (based on our latest America After 3PM special report, The Growing Importance of Afterschool in Rural Communities)
- Strategies to build support for STEM education
- Healthy Eating and Physical Activity (HEPA) standards in afterschool
Join the excitement! Take the Virtual Challenge
You can play a major role in boosting the voice of advocates visiting Congress by taking the Virtual Afterschool for All Challenge in your community.
Right now, you can help the most by sending a message to your representatives, asking them to increase funding levels for 21st CCLC by $133 million for FY2017, bringing the total to $1.3 billion and allowing 140,000 additional children to access afterschool, before-school and summer learning programs.
In just a single click, you can add your voice to our Thunderclap, which sends a syncronized blast of messages supporting afterschool on social media. If you're seeking a deeper way to get involved—and a lasting impact for your community—learn about setting up a site visit to your program.
learn more about:
Webinar recap: A new vision for STEM with the Framework for K-12 Science Education
By Erin Murphy
Last month, in partnership with the Research + Practice Collaboratory, we hosted a webinar discussing the National Research Council's Framework for K-12 Science Education and what it means for afterschool. The following speakers shared their expertise:
- Bronwyn Bevan, Senior Research Scientist at the University of Washington
- Katherine McNeill, Associate Professor of Science Education at Boston College
- Emily McLeod, Director of Curriculum at Techbridge
- Tracy Truzansky, Project Manager for Training at Vermont Afterschool
Bronwyn started the webinar off by introducing the Framework for K-12 Science Education, a report that articulates a new vision of science, technology, engineering, and math (STEM) education needed for the 21st century. Its goal is to spell out exactly what all students need upon high school graduation in order to apply science to their daily life, critically consume science in the public sphere and go into the careers of their choice. Building on current research on how people best learn science, the Framework defines three key dimensions of STEM learning:
- Disciplinary Core Ideas: These include broad topic areas within the sciences, engineering and technology, such as chemistry, physics and earth sciences. There are fewer content areas, allowing students to delve deeper into each one.
- Cross-cutting themes: These themes, such as patterns, energy, and structure, connect across fields of science and are taught as part of all the disciplinary core ideas.
- STEM practices: These practices focus on sense-making from investigations, which entails using evidence from investigations to develop the best explanations.
learn more about: Events and Briefings Science Community Partners
Weekly Media Roundup: May 18, 2016
By Luci Manning
Students Jump into Club (Norwich Bulletin, Connecticut)
Earlier this year, Sterling Community School students were treated to a visit from a jump-rope expert who inspired them to start their own afterschool jump-rope program. The students have done all the work to make the club a reality – they put together a proposal, made flyers, created permission slips and developed a schedule. Principal Shari Ternowchek said the club is a great way for students to stay healthy and build a sense of camaraderie. "It really opened the doors to the quiet, shy kids," she told the Norwich Bulletin.
NYC Teens Head to Flint to Bring Relief to Water Crisis (Newsday, New York)
When New York City students in the YMCA's afterschool program learned about the Flint water crisis, they decided to hold a water drive that would eventually collect 300 bottles of water and donations for filters. But for six teens, that wasn't enough – they personally made the trek to Michigan to deliver the donations themselves. Sixteen-year-old Fahme Ibrahim's family struggled without water after Superstorm Sandy, so he said he could relate to Flint residents as they deal with their contaminated water supply. "Knowing that Flint was out of water for a longer period of time, it was unimaginable," he told Newsday. "I wanted to make sure we could give back."
Future Docs Go to Cooking Class (Philadelphia Inquirer, Pennsylvania)
Medical students from Rutgers' Robert Wood Johnson Medical School are trying to mitigate diseases like obesity and diabetes by bringing their medical knowledge to an afterschool cooking class in New Brunswick. RWJ encourages its students to participate in community service, and after seeing the role food choices play in many of these diseases, three students – Sally Vitez, Jaclyn Portelli Tremont and Melissa Villars – decided this was the best way they could start to treat the next generation. "With the epidemic of childhood obesity in this country, we felt an obligation, as future physicians, to try and teach kids how much the food they eat is directly related to their health," Vitez told the Philadelphia Inquirer. The class gives students lessons in moderation and a plethora of healthy recipes to try at home.
Refuge for Refugees (Tucson Weekly, Arizona)
For two hours every Wednesday, documentary filmmaker Özlem Ayse Özgür teaches filmmaking techniques to refugee teenagers as part of the Owl and Panther Youth Film Project. The art therapy program hopes to give these students a set of valuable multimedia skills while building a community of friends and mentors for teens who may feel out of place in their new country. Over the course of the four-month program, each student creates a short self-portrait as well as a longer film about the meaning of "home." Owl and Panther administrative manager Abby Hungwe said the program has helped students build their confidence and take on leadership roles. "I think with any work that you do with kids, the reward is seeing their growth and seeing them push through something that may have begun as a weakness and converting that into a success," she told Tucson Weekly.
learn more about: Science Arts Youth Development Community Partners


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HourlyHours to be determined
Job Description
we are looking for a writer that:
is GREAT at conversational writing, for blogs
we need an EXCELLENT content writer
this writer will write for us. . and eventually our clients.
we will give general outline of content. . and the "tone" of what we are looking for.
we are looking for a long term relationship. .
a) so if you are looking to build a relationship --
b) we would like to see your portfolio as well.
Of course communication skills and fluency in English is a must.
Communication and our ability to reach you is very important. We are on EST
Skills: writing, english
About the Client
Whitby 07:29 AM
Jobs Posted
53% Hire Rate, 3 Open Jobs
Over $30,000
Total Spent
161 Hires, 14 Active
Avg Hourly Rate Paid
6,503 Hours


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Top Definition
an aggressive blow job with lots of spit and wax on wax off circular motions on the balls
by AdubP May 11, 2010
A hired professional who licks the shit off the dicks of men after a gay orgy.
Jason is such a cock buffer.
Why don't you just go buff a few cocks.
Is there a cock buffer in the house?
Why don't you just go buff a few cocks.
Is there a cock buffer in the house?
by Bernard Lebowski January 09, 2004
Someone who buffs cock, cleaning every inch of it with their mouth. Not unlike buffing a dirty car.
"I hate that son of a bitch Mike, he is such a cock buffer"
by Tical January 17, 2005
When a male or female whatever floats your boat buffs your cock or sucks it clean
Dude do you know hailey?
Yea man shes a cockbuffer!
Yea man shes a cockbuffer!
by pootietang March 16, 2008
someone who thoroughly enjoys "spit shinning" another males penis.
X0X0Beans (Peterson Beans) is a real cock buffer.
by UD January 28, 2003
A queerbait, see also Dave K Rad
That dave K rad can sure buff a cock, he is a swell cock buffer
by Deezy January 28, 2003


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Fun for the Whole Pack at a Grapevine Water Park Resort
Great Wolf Lodge • Grapevine, TX
Escape Kit
- A One-Night Stay for Up to Six People in a KidKamp Suite, Sundays Through Thursdays ($229)
- Or, a Two-Night Stay for Up to Six People in a Family Suite, Sundays Through Thursdays ($369)
- Water Park Wristbands for Up to Six People
- $25 Resort Credit per Night
- Valid for Stays from Now to December 3, 2015
- Combine Vouchers to Stay for Up to Four Nights
- After Purchase, Follow Your Voucher's Redemption Instructions to Complete Your Reservation
Treat your kids to a winter full of wild and wet fun with a stay at this enormous, family-friendly indoor water park.
The Destination
Everything's bigger in Texas, so it's no wonder that Grapevine's Great Wolf Lodge resort is one of the biggest in the country. At this 80,000-square-foot indoor water park, the regulated temperature hovers around a balmy 84 degrees. Jump in an inner tube and swirl through the six-story funnel of the Howlin' Tornado, or zip down the three-story water slides of Totem Towers. Later, zoom in and out of the Lodge on the slides of Alberta Falls, float along the lazy river, then dry off for the host of other resort attractions.
The Digs
Kids run the show at Great Wolf Lodge—just look at the family-friendly accommodations. The KidKamp suites feature a fun in-room tent with bunk beds inside, as well as a normal queen-size bed for Mom and Dad. All rooms have at least one TV, a full bathroom, microwave, fridge, and other convenient amenities. Best of all, the Lodge is just minutes from the massive Grapevine Mills Mall, so it's a breeze to get out there and shop 'til you drop.
The Diversions
When it's time for drier activities, head to the interactive MagiQuest, which gives kids a magic wand to use against goblins while searching for hidden treasure. Scooops Kid Spa pampers kids with ice cream-themed manicures and other treatments—while grown-ups can enjoy treatments at Elements Spa Salon. At dinner time, even picky eaters will marvel at the options available in the massive menu at the Lodge Wood Fired Grill. Between the incredible water slides and the fun accommodations, this quick trip to the Grapevine's Great Wolf Lodge makes for a family vacation that proves bigger is better.
The Details
• 13% tax and $19.99 resort fee not included—you'll pay those directly to the property
• Plan around the blackout dates: November 26-27, 2015
We were most impressed by the staff. They are all friendly. We never saw any staff who was not smiling. [...] This was our second visit and will not be our last.-- LivingSocial Member
Great value for a spacious room, very clean facility, and water park access for the day you check in AND the day you check out! My boys LOVED IT!-- LivingSocial Member
escapes 30-day promise
LivingSocial gives you up to 30 days to return your unused voucher for a full refund. Once you've made a reservation, you are subject to the merchant's cancellation and refund policy. If you want to secure your preferred dates of travel, we strongly recommend that you complete reservation with the merchant within 30 days of your purchase—after that, LivingSocial will not issue any refunds.
the fine print
- Limit 2 per customer, up to 2 additional as gifts; up to 2 vouchers may be combined to extend stay
- Only valid for stays now to December 3, 2015
- Nights must be spent consecutively; all inclusions must be redeemed during one stay
- Must be 21 or over to check-in
- Online reservations required and subject to availability
- Merchant cancellation/re-scheduling policy of 3 days in advance of scheduled arrival; voucher subject to forfeiture
- Not valid toward existing or room block reservations
- Voucher includes water park wristbands for up to 6 people and $25 resort credit per night
- 13% tax and $19.99 resort fee not included; payable directly to the property
- Incidental charges, charges for additional services, and gratuity at the property are not included
- Voucher valid for 6 guests
- Children are welcome at the property
- Blackout date(s): November 26 to 27, 2015
- Other conditions apply • PAID AND PROMOTIONAL VALUES EXPIRES ON December 3, 2015 • PAID VALUE DOES NOT EXPIRE • PAID VALUE EXPIRES ON December 3, 2020 • PROMOTIONAL VALUE EXPIRES ON December 3, 2015 • Enjoy By December 3, 2015
Other conditions apply
Except where noted in the fine print:
• Cannot be combined with any other offer or promotion
• Tax and gratuity are not included
• Merchant is responsible for the quality of the products or services provided to you at redemption
• LivingSocial Terms and Conditions - https://www.livingsocial.com/terms
Original Price:
- 0% savings
- remaining


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HR Journals: Academic and Practioner
Human Resources Management Resources
HR in the News
SHRM Society for Human Resource Management
International HR resources Look for recommendations just for this course.
Knowledge@Wharton Human Resources. Reports of research by faculty at University of Pennsylvania's Wharton School of Business
McKinsey & Co.
Major News Sources Factiva
Access current and past issues of NYT, WSJ, LA Times
SD Union Tribune, San Diego Business Journal,
SanDiegoSource The Daily Transcript -- Contact Business Librarian for access
3 ways to search for articles.
Library Catalog Search by individual journal title See video clip: Journal title in library catalog
Discovery Search (narrow your choices on the left navigation bar)
Caution this method is like "google inside the library"
All Business Databases (optional login at the library home page, we know what courses you take and will populate databases to your preferences)
Library Database Subscriptions from HR approved journals and trade magazines
Search these recommended databases by your topic and narrow to approved journal titles.
ABI Inform
Business Source Premier (BSP) Most of your tiltes are available through BSP --good place to start
Emerald Full Text (UK publisher with international content)
Science Direct
Wiley Online Are availabe.
Academy of Management Journal (BSP) also HD28 .A24 Periodicals
Academy of Management Review (BSP) also HD28 .A23
Administrative Science Quarterly (BSP) also HD28 .A25
California Management Review (BSP) also HD28 .C18
Employee Relations Law Journal (BSP)
Employee Responsibilties and Rights Journal (Springer)
Human Relations (BSP) HD1 .H8
Human Resource Development Quarterly (Wiley Online)
Human Resource Management (Wiley Interscience)
Human Resource Management Review (ScienceDirect)
Industrial & Labor Relations Review (LexisNexis Academic, JSTOR-no full text for latest 3 years)
Industrial Relations (Blackwell Synergy)
International Journal of Human Relations (BSP)
International Journal of Human Resource Management (BSP-no full text for latest 18 months)Z
Journal of Applied Psychology (PsychArticles Ebsco)
Journal of Business Ethics (Springer)
Journal of Collective Negotiation in the Public Sector (BSP)
Journal of Labor Research (BSP)
Journal of Management (BSP) also HD28 .J597
Journal of Occupational and Organizational Psychology (BSP)
Journal of Organizational Behavior (Wiley Interscience)
Journal of Vocational Behavior (ScienceDirect)
Labor Law Journal (ABI Inform Global)
Labor Studies Journal (BSP)
People and Strategy (Business Source Premier) previously Human Resource Planning
Personnel Psychology (BSP) also HF5549 .A2 P53
Public Personnel Management (ABI Inform Global, CINAHL Plus)
Not owned by this library: Request Interlibrary Loan (ILL)
Organization Behavior & Human Decision Processes
Academy of Management Executive (BSP)
Across the Board (BSP)
ASTD Training and Development (ABI Inform)
Business Horizons (ScienceDirect)
Harvard Business Review (BSP)
HR Magazine (BSP)
HR Focus (previously Personnel) (BSP)
Management Review (ceased publication 2000)
Personnel Journal now Workforce Management (ABI Inform)
Organizational Dynamics (ScienceDirect)
Training (ABI Inform) each issue includes a country focus article
Training and Development (ABI Inform)
Workforce Management (previously Personnel Journal) (BSP)
Journal Changes
Personnel -- Name Change -- Continued by HR Focus
Supervisory Management -- No longer published
Last Update: February 09, 2015 06:12


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Leading and Managing People
Module overview
- Managing people for effective performance through the life cycle of employment
- Managing day to day performance
- Dealing with performance issues
- Understanding individual's motivation, personality, and behaviours
- Developing appropriate, effective people management responses
- Leading and developing your staff
On completion of the course you will have developed an understanding of best practice in terms of managing staff performance and will have developed a range of skills to enhance your ability to routinely lead and manage staff. You will have increased your understanding of the behaviours and motivation of others and explored a range of tactics to engage staff and improved your own ability to manage staff performance.
Duration, attendance and delivery
You will start with 2 full day interactive workshops usually in weeks 1 and 4. There will also be a mix of on-line, flexible, facilitated learning and some self-study. 1-1 tutorials are available to support you to meet the assessment requirements.
The module will last approximately 10 weeks. Notionally a 10-credit module means an average of around 100 learning hours; this includes attendance at workshops, tutorials, self-study, reflection, learning and application at work as well as completing activities and assessments.
We also provide support with study skills for those who are new to study at this level or who may not have studied for some time.
At the end of the module you will undertake an assessment. This is a work based assessment rather than just a theory based essay. Typically you will be required to apply what you have learnt to your practice, evaluating concepts for their applicability and usefulness.
The assessment format may be a written exercise, in-class presentation, project report or another appropriate method. To give you an indication, a written piece would be around 2000 words in length.
Entry requirements
You will need to be in a work role (paid or unpaid) which allows you the scope to put the concepts learned into practice. There are no formal qualification requirements for entry; we assess suitability on each individual application. Please contact us if you would like further details of our admissions policy.


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Kelly Clarkson – Don't Rush – Academy of Country Music Awards 2013 – Video
Kelly Clarkson sang "Don't Rush" at the Academy of Country Music Awards 2013. Watch the video here:
I love this song! I can't believe it's been 11 years.
The Latest on Kelly Clarkson
All posts on Kelly Clarkson
Follow me on Facebook! • Follow me on Google+


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My car has recentely been not starting since the warmer weather has came. When I try to restart the car, everything inside the car will work, (radio, windows, air, lights, etc) but absolutely nothing happens when I turn the key. The battery and alternator are brand new, so I don't believe that is the problem. Can anyone please help me on this???
by jenven in Cincinnati, OH on June 17, 2011


text:
Newegg.com - A great place to buy computers, computer parts, electronics, software, accessories, and DVDs online. With great prices, fast shipping, and top-rated customer service - once you know, you Newegg.
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Newegg.com - Computer Parts, Laptops, Electronics, HDTVs, Digital Cameras and More!
Sold and Shipped by tradeCOzone
Woolite Foam Carpet Cleaner - Heavy Traffic foam with Stain Defense . Cleans even gritty, greasy, ground-in dirt. Safe, gentle way to clean your entire carpet. Combines the advanced technology of a fabric refresher with the cleaning power of a rug cleaner. Formulated with acrylic polymers to help repel dirt and stains, so it's easier to clean the next time. 22 oz. - Size: 22 oz, Type: Foam Aerosol, Pkg Qty: 1, Package Type: Can
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text:
The former left Hofmann shrubs GmbH decrease/go back to the 1839 created institute for building of cars Gottfried left one. Since that time it came up 1998 in the ALSTOM company and firmiert as ALSTOM LHB GmbH. It manufactures further rail-mounted vehicles.
We found here 7 articles.
L» Left Hofmann shrubs
» LIMA Locomotive Works
» Lokomotivbau electrotechnical works
» Lokomotivfabrik Floridsdorf
» Lokomotivfabrik Luhansk
» Lokomotivfabrik the bar
Index | Privacy | Terms Of Use | Sitemap | Feedback


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On Blogger since February 2005
Profile views - 6406
My blogs
Blogs I follow
- Bean Queen and SuperBoy
- Little Bits
- Minori Design
- Mom's Knitting Room
- Notes to self
- Ohhh Lulu...
- One Funky Munky
- Root Simple
- Sewspicious Minds
- Simply Stephy
- So, the thing is...blog
- Sophie and Theo's Blog
- The Hem Line
- The Linear Legume
- Tiny's Kitchen Table
- Tonya's Knitting Knotes
- Vintage Sewing Patterns
|Tennessee, United States
|I'm an artist and a geek. Sometimes I knit and sew.
|sewing toymaking knitting fiber arts spinning drawing weaving printmaking wool
|Favorite Movies
|amelie, bubba-hotep
|Favorite Music
|classical, acoustic alchemy
|Favorite Books
|most of them, antique books are as indispensable as chocolate and coffee
Unlike a dog, how can a turtle ever be naked?
When the turtle is in the dog, and the dog is playing with the shell. Poor turtle :o(


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A program for young children this week will highlight Dr. Seuss.
Friday�s Stepping Stones, for children ages 2 to pre-K, will focus on �Seusspicious Behavior.� The event will include music, story time, games, crafts and a snack at Kerr Street Rec Center from 10 to 11 a.m. It costs $5 for city residents and $7 for non city residents.
For more information, call 910-938-5312.
Location, ST | website.com


text:
This timeless beauty is the perfect addition to any home.
Carlysle High Back Sofa
Currently Out of Stock
Product Number: 794307p
Taken from the era when comfort was king, the Carlysle Collection features ultra high back seating for that "sink in comfort". The subtle gold tones in the weave sparkle in the sunshine and bring added warmth to this timeless collection. Made of all-weather resin. This Carlysle sofa is the perfect place to entertain friends or read your favorite book.
Dimension: 30"L x 85.5"W x 36"H; 125 lbs.
Dimension: 30"L x 85.5"W x 36"H; 125 lbs.
read more...


text:
GREENHUT: Saving the Earth, one fraud at a time
SACRAMENTO ---- If the theory of man-made global warming were such a self-obvious truth, the result of scientific consensus, then why do advocates for this idea keep committing frauds to advance it? Even more disturbing, why are some writers willing to defend this behavior?
The latest embarrassment for global-warming activists came on Feb. 20 after Peter Gleick, founder of the Pacific Institute for Studies in Development, Environment and Security in Oakland, admitted that he committed fraud to obtain documents he thought would embarrass a conservative think tank that has been a leading debunker of some of the overheated claims of the climate-change Chicken Littles.
The memos, which reveal the group's political and fundraising strategies, provided little to embarrass the Chicago-based Heartland Institute, but it has damaged the reputation of a man who was a respected intellectual in the environmental world.
Gleick, a MacArthur Foundation "genius" fellow, doesn't seem brilliant now, as he takes a leave of absence from the institute, faces public embarrassment and possible prosecution. Heartland claims that one memo was fabricated, although Gleick denies that charge, but the scandal could get uglier.
But even after Gleick admitted and apologized for his action, Los Angeles Times columnist Michael Hiltzik defended him: "It's a sign of the emotions wrapped up in the global warming debate that Gleick should be apologizing for his actions today while the Heartland Institute stakes out the moral high ground."
"Peter Gleick lied, but was it justified by the wider good?" asked James Garvey of the British Guardian newspaper. He compared Gleick's action to that of a man who lied to keep his friend from driving home drunk. "What Heartland is doing is harmful, because it gets in the way of public consensus and action," he argued. "If his lie has good effects overall ---- if those who take Heartland's money to push skepticism are dismissed as shills, if donors pull funding after being exposed in the press ---- then perhaps on balance he did the right thing. ... It depends on how this plays out."
In his view, anything that gets in the way of "consensus" ---- i.e., everyone agreeing with Garvey ---- is dangerous, so why not cheat, as long as it "has good effects"? Let's reserve judgment based on how it plays out.
What would these people argue if a conservative who argues that, say, public-sector unions are bankrupting the state, pulled a similar fraud to get his hands on documents from union officials? Would they be defending that? Of course not.
These writers are advancing a Machiavellian political agenda, not advancing a consistent ethical principle.
When it comes to global warming, the ends apparently justify the means. People from all political persuasions do stupid things to advance their cause, but what bothers me most are respectable people who justify behavior they would never tolerate from their foes. That type of ideological fanaticism is corrosive of our democratic society.
It's easy to chide the hypocrisy of Gleick. He had been the chairman of an ethics committee for a scientific association. His column blasting dishonesty still sits on his institute's website. It's harder to explain away his deceit as a mere aberration in the climate-change drama.
In the "Climategate" scandal in 2009, "Hundreds of private email messages and documents hacked from a computer server at a British university are causing a stir among global warming skeptics, who say they show that climate scientists conspired to overstate the case for a human influence on climate change," according to a New York Times report from the time.
The emails showed that the scientific community is so invested in this climate-change ideology for financial and ideological reasons that it would rather cook the numbers than level with the public about the reality of the threat. A follow-up release of emails in 2011 provided even more evidence supporting skeptics' claims.


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Are you Lina Wang?Claim your profile
Publications (8)44.19 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: SHP2 is an allosteric phosphatase essential for growth factor-mediated Ras activation. Germ-line mutations in SHP2 cause clinically similar LEOPARD and Noonan syndromes, two of several autosomal-dominant conditions characterized by gain-of-function mutations in the Ras pathway. Interestingly, Noonan syndrome SHP2 mutants are constitutively active, whereas LEOPARD syndrome SHP2 mutants exhibit reduced phosphatase activity. How do catalytically impaired LEOPARD syndrome mutants engender gain-of-function phenotypes? Our study reveals that LEOPARD syndrome mutations weaken the intramolecular interaction between the N-SH2 and phosphatase domains, leading to a change in SHP2 molecular switching mechanism. Consequently, LEOPARD syndrome SHP2 mutants bind upstream activators preferentially and are hypersensitive to growth factor stimulation. They also stay longer with scaffolding adapters, thus prolonging substrate turnover, which compensates for the reduced phosphatase activity. The study provides a solid framework for understanding how individual SHP2 mutations cause diseases.
Article: Discovery and Evaluation of Novel Inhibitors of Mycobacterium Protein Tyrosine Phosphatase B from the 6-Hydroxy-Benzofuran-5-Carboxylic Acid Scaffold.[Show abstract] [Hide abstract] ABSTRACT: Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (mPTPB) is a virulence factor secreted by the pathogen and mediates mycobacterial survival in macrophages by targeting host cell immune responses. Consequently, mPTPB represents an exciting new target to combat TB infection. We describe a medicinal chemistry-oriented approach that transforms a benzofuran salicylic acid scaffold into a highly potent (IC50 = 38 nM) and selective mPTPB inhibitor (>50 fold against a large panel of PTPs). Importantly, the inhibitor is capable of reversing the altered host immune responses induced by the bacterial phosphatase and restoring the macrophage's full capacity to secrete IL-6 and undergo apoptosis in response to IFN-γ stimulation, validating the concept that chemical inhibition of mPTPB may be therapeutically useful for novel TB treatment. The study further demonstrates that bicyclic salicylic acid pharmacophores can be used to deliver PTP inhibitors with high potency, selectivity, and cellular efficacy.
Article: A Highly Selective and Potent PTP-MEG2 Inhibitor with Therapeutic Potential for Type 2 Diabetes[Show abstract] [Hide abstract] ABSTRACT: Protein tyrosine phosphatases (PTPs) constitute a large family of signaling enzymes that control the cellular levels of protein tyrosine phosphorylation. A detailed understanding of PTP functions in normal physiology and in pathogenic conditions has been hampered by the absence of PTP-specific, cell-permeable small-molecule agents. We present a stepwise focused library approach that transforms a weak and general non-hydrolyzable pTyr mimetic (F(2)Pmp, phosphonodifluoromethyl phenylalanine) into a highly potent and selective inhibitor of PTP-MEG2, an antagonist of hepatic insulin signaling. The crystal structures of the PTP-MEG2-inhibitor complexes provide direct evidence that potent and selective PTP inhibitors can be obtained by introducing molecular diversity into the F(2)Pmp scaffold to engage both the active site and unique nearby peripheral binding pockets. Importantly, the PTP-MEG2 inhibitor possesses highly efficacious cellular activity and is capable of augmenting insulin signaling and improving insulin sensitivity and glucose homeostasis in diet-induced obese mice. The results indicate that F(2)Pmp can be converted into highly potent and selective PTP inhibitory agents with excellent in vivo efficacy. Given the general nature of the approach, this strategy should be applicable to other members of the PTP superfamily.
Article: Substrate Specificity of Lymphoid-specific Tyrosine Phosphatase (Lyp) and Identification of Src Kinase-associated Protein of 55 kDa Homolog (SKAP-HOM) as a Lyp Substrate[Show abstract] [Hide abstract] ABSTRACT: A missense single-nucleotide polymorphism in the gene encoding the lymphoid-specific tyrosine phosphatase (Lyp) has been identified as a causal factor in a wide spectrum of autoimmune diseases. Interestingly, the autoimmune-predisposing variant of Lyp appears to represent a gain-of-function mutation, implicating Lyp as an attractive target for the development of effective strategies for the treatment of many autoimmune disorders. Unfortunately, the precise biological functions of Lyp in signaling cascades and cellular physiology are poorly understood. Identification and characterization of Lyp substrates will help define the chain of molecular events coupling Lyp dysfunction to diseases. In the current study, we identified consensus sequence motifs for Lyp substrate recognition using an "inverse alanine scanning" combinatorial library approach. The intrinsic sequence specificity data led to the discovery and characterization of SKAP-HOM, a cytosolic adaptor protein required for proper activation of the immune system, as a bona fide Lyp substrate. To determine the molecular basis for Lyp substrate recognition, we solved crystal structures of Lyp in complex with the consensus peptide as well as the phosphopeptide derived from SKAP-HOM. Together with the biochemical data, the structures define the molecular determinants for Lyp substrate specificity and provide a solid foundation upon which novel therapeutics targeting Lyp can be developed for multiple autoimmune diseases.
- [Show abstract] [Hide abstract] ABSTRACT: SHP2, encoded by PTPN11, is a non-receptor protein tyrosine phosphatase (PTP) containing two tandem Src homology-2 (SH2) domains. It is expressed ubiquitously and plays critical roles in growth factor mediated processes, primarily by promoting the activation of the RAS/ERK signaling pathway. Genetic and biochemical studies have identified SHP2 as the first bona fide oncoprotein in the PTP superfamily, and a promising target for anti-cancer and anti-leukemia therapy. Here, we report a structure-based approach to identify SHP2 inhibitors with a novel scaffold. Through sequential virtual screenings and in vitro inhibition assays, a reversible competitive SHP2 inhibitor (C21) was identified. C21 is structurally distinct from all known SHP2 inhibitors. Combining molecular dynamics simulation and binding free energy calculation, a most likely binding mode of C21 with SHP2 is proposed, and further validated by site-directed mutagenesis and structure-activity relationship studies. This binding mode is consistent with the observed potency and specificity of C21, and reveals the molecular determinants for further optimization based on the new scaffold.
- [Show abstract] [Hide abstract] ABSTRACT: SHP2 phosphatase is a positive transducer of growth factor and cytokine signaling. SHP2 is also a bona fide oncogene; gain-of-function SHP2 mutations leading to increased phosphatase activity cause Noonan syndrome, as well as multiple forms of leukemia and solid tumors. We report that tautomycetin (TTN), an immunosuppressor in organ transplantation, and its engineered analog TTN D-1 are potent SHP2 inhibitors. TTN and TTN D-1 block T cell receptor-mediated tyrosine phosphorylation and ERK activation and gain-of-function mutant SHP2-induced hematopoietic progenitor hyperproliferation and monocytic differentiation. Crystal structure of the SHP2⋅TTN D-1 complex reveals that TTN D-1 occupies the SHP2 active site in a manner similar to that of a peptide substrate. Collectively, the data support the notion that SHP2 is a cellular target for TTN and provide a potential mechanism for the immunosuppressive activity of TTN. Moreover, the structure furnishes molecular insights upon which therapeutics targeting SHP2 can be developed on the basis of the TTN scaffold.
- [Show abstract] [Hide abstract] ABSTRACT: Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), is a major worldwide threat to public health. Mycobacterium protein tyrosine phosphatase B (mPTPB) is a virulent phosphatase secreted by Mtb, which is essential for the survival and persistence of the bacterium in the host. Consequently, small-molecule inhibitors of mPTPB are expected to serve as anti-TB agents with a novel mode of action. Herein, we report the discovery of highly potent and selective mPTPB inhibitors using a novel, double Click chemistry strategy. The most potent mPTPB inhibitor from this approach possesses a K(i) value of 160 nM and a >25-fold selectivity for mPTPB over 19 other protein tyrosine phosphatases (PTBs). Molecular docking study of the enzyme-inhibitor complex provides a rationale for the high potency and selectivity of the lead compound and reveals an unusual binding mode, which may guide further optimization effort.
Article: Salicylic Acid Based Small Molecule Inhibitor for the Oncogenic Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (SHP2)[Show abstract] [Hide abstract] ABSTRACT: The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with Noonan syndrome, various kinds of leukemias, and solid tumors. Thus, there is considerable interest in SHP2 as a potential target for anticancer and antileukemia therapy. We report a salicylic acid based combinatorial library approach aimed at binding both active site and unique nearby subpockets for enhanced affinity and selectivity. Screening of the library led to the identification of a SHP2 inhibitor II-B08 (compound 9) with highly efficacious cellular activity. Compound 9 blocks growth factor stimulated ERK1/2 activation and hematopoietic progenitor proliferation, providing supporting evidence that chemical inhibition of SHP2 may be therapeutically useful for anticancer and antileukemia treatment. X-ray crystallographic analysis of the structure of SHP2 in complex with 9 reveals molecular determinants that can be exploited for the acquisition of more potent and selective SHP2 inhibitors.
Top Journals
University of Wisconsin–Madison
Madison, Wisconsin, United States
- Division of Pharmaceutical Sciences