A clamp assembly is provided for securing to preexisting studs or support members. The clamp assembly comprises a compression fitting adapted to be secured to a plurality of different sized studs or wall supports, and further to support additional supports including, but not limited, horizontal support members. A support and movement device is further provided that is selectively connectable to clamp and support members of the disclosure.
1. A selectively removable apparatus for interconnection to a pre-existing support member, the apparatus comprising: a clamp comprising a first member and a second member, each of the first member and the second member comprising a face plate adapted to contact a support member and apply a compression force thereto; the first member and the second member comprising a plurality of extensions provided substantially perpendicular to the face plates, and wherein void spaces are provided between at least some of the plurality of extensions; a fastener extending through the first member and the second member, and wherein the fastener is adapted to provide a compression force on the clamp and a support member provided between the first member and the second member.
2. The apparatus of claim 1, further comprising a transport device which is operably engaged to the clamp.
3. The apparatus of claim 2, wherein the transport device includes wheels on a distal end.
4. The apparatus of claim 1, further comprising at least one secondary support member, wherein the secondary support member comprises a substantially horizontally extending bar or beam for supporting various objects.
5. The apparatus of claim 4, wherein the support member extends through at least one of the void spaces.
6. The apparatus of claim 1, wherein the second member comprises a substantially L-shaped bracket operable to be secured to a wall stud.
7. The apparatus of claim 1, further comprising at least one of a shear pin and a bolt extending through at least one of the first member and the second member.
8. A system for selective interconnection to a pre-existing support member, the system comprising: a clamp comprising a first member and a second member, each of the first member and the second member operable to contact a support member and apply a compression force thereto; the first member and the second member comprising a plurality of extensions, and wherein void spaces are provided between at least some of the plurality of extensions; a threaded fastener extending through the first member and the second member, and wherein the fastener is adapted to provide a compression force on the clamp, the compression force operable to secure the clamp to a pre-existing support member; a transport device operatively engaged to the clamp; and at least one secondary support member, wherein the secondary support member comprises a substantially horizontally extending bar or beam for supporting various objects.
9. The system of claim 8, wherein the transport device comprises a dolly.
10. The system of claim 9, wherein the clamp is secured to the secondary support member.
11. The system of claim 10, wherein the support member extends through at least one of the void spaces.
12. The system of claim 8, wherein the second member comprises a substantially L-shaped bracket operable to be secured to a wall stud.
13. The system of claim 8, further comprising at least one of a shear pin and a bolt extending through at least one of the first member and the second member.
14. A system for selective interconnection to a pre-existing support member, the system comprising: a clamp comprising a first member and a second member, each of the first member and the second member operable to contact a support member and apply a compression force thereto; the first member and the second member comprising a plurality of extensions provided substantially perpendicular to the face plates, and wherein void spaces are provided between at least some of the plurality of extensions; at least one secondary support member extending through at least one of the void spaces, wherein the secondary support member comprises a substantially horizontally extending bar or beam; a threaded fastener extending through the first member and the second member, and wherein the fastener is adapted to provide a compression force on the clamp, the compression force operable to secure the clamp to at least one of a wall stud and the secondary support member.
15. The system of claim 14, wherein the at least one secondary support member comprises at least one lift point for receiving a load.
16. The system of claim 14, wherein the secondary member comprises a substantially L-shaped bracket operable to be secured to a wall stud.
17. The system of claim 14, further comprising at least one of a shear pin and a bolt extending through at least one of the first member and the second member.
18. The system of claim 14, wherein the first member comprises three pairs of adjacent extensions, and two pair of corresponding void spaces.
19. The system of claim 18, wherein the system comprises a plurality of secondary support members, and wherein the secondary support members extend through the void spaces.
20. The system of claim 17, wherein the at least one of a shear pin and a bolt comprises a threaded bolt extending through the first member and the second member.
 This U.S. Non-Provisional Patent Application claims the benefit of priority from U.S. Provisional Patent Application Ser. No. 62/205,327, filed Aug. 14, 2015, the entire disclosure of which is incorporated by reference herein.
 The present disclosure relates to clamps and fasteners and devices for connecting to such features. More specifically, the present disclosure relates to a unique clamp for attaching items to preexisting framing stud members. Such items include horizontal support members and various other features to be supported by an existing stud or support, and load-bearing transport devices for supporting, moving and positioning modular building structures such as modular rooms.
 Various embodiments of the present disclosure provide new and useful universal framing stud clamp members. Such embodiments provide devices for securely attaching and securing items such as load bearing bars to framing stud members.
 It is one aspect of the present invention to provide a universal framing stud clamp that can be selectively secured to a plurality of different sized features, such as studs of different profiles and gauges.
 In one embodiment, a clamp adapted for interconnection to a pre-existing support member is provided, the clamp comprising a first member and a second member, each of the first member and the second member comprising a face plate adapted to contact a support member and apply a compression force thereto. The first member and the second member comprise a plurality of extensions or projections provided substantially perpendicular to the face plates, and void spaces are provided between at least some of the plurality of extensions. A fastener extends through the first member and the second member, and the fastener provides a compression force on the clamp and a support member provided between the first member and the second member.
 It is another object of the present disclosure to provide a new and useful moving and positioning device which is more efficient in use and operation and more universally functional and versatile in application and operation than known prior art attachment devices. It is a further object of the present disclosure to provide such a device that is adapted for use with modular building structures, such as modular or prefabricated rooms.
 In various embodiments, the present disclosure provides a modular building moving and positioning device that is adapted to move and position modular building or room structures such as bathrooms, kitchens, classrooms, offices, or other modular rooms whether or not specifically referred to herein and which will be recognized by one of skill in the art.
 It is also an object of the present disclosure to provide a moving and positioning device comprising the ability to connect to various wall stud profiles and gauges, such that a single transport device is suitable for use with various objects of different size and shape.
 U.S. Pat. No. 7,914,017 to Setzer Sr., which is incorporated by reference herein in its entirety, discloses a hand truck with an electronic module, a scale and a control unit. Although various features of Setzer Sr. are contemplated for use in embodiments of the present disclosure, the present disclosure further provides features wherein a hand truck or moving device is adapted to secure to various preexisting support features as shown and described herein.
 U.S. Pat. No. 3,631,999 to Keinrich et al., which is hereby incorporated by reference in its entirety, discloses a transporting device with vertical lifting means. Keinrich, however, fails to disclose various features of the present invention including, for example, a device that is adapted to secure to modular building structures and related features.
 In certain embodiments, the support, moving and positioning devices disclosed herein are used for moving and lifting stud framed structures into position. Such devices can be separated into sections for easy attachment, and improved productivity on site. A sliding clamp design allows a jack to be positioned on various stud spacing for optimized locating of the jack. Devices of the present disclosure comprise the ability to attach to stud framed walls and lift the unit sufficiently to remove a pallet and subsequently lower the unit completely into a recessed depression, for example. Traditionally this operation would require multiple devices, and significantly more effort of the device, applying equal even pressure to the load bars.
 In various embodiments, a method of manipulating and/or transporting a modular building structure is provided. In one embodiment, a method of manipulating a modular building structure comprises the steps of providing a moveable support member for connection to a modular building unit, the support member comprising a horizontal support member with at least one wheel secured thereto, a telescoping vertical support member, a user-interface for selectively extending and retracting said vertical support member, and a load bearing interface for selective attachment to a fixed object. A clamp is provided, the clamp adapted for interconnection to a pre-existing support member and comprising a first member and a second member, each of the first member and the second member comprise a face plate adapted to contact a support member and apply a compression force thereto. The first member and the second member comprise a plurality of extensions or projections provided substantially perpendicular to the face plates, and void spaces are provided between at least some of the plurality of extensions. A fastener extends through the first member and the second member, and the fastener provides a compression force on the clamp and a support member provided between the first member and the second member. The method comprises a step of securing the clamp to at least one structural support which, in certain embodiments, comprises a wall stud or frame member of the modular building unit. The clamp is secured to the structural support at least in part by application of a force to the fastener. At least one horizontal support is provided that extends from or through and is provided in force transmitting communication with the modular building structure by way of the clamp. Once the clamp is secured, the method comprises the step of selectively interconnecting the moveable support member to at least one of the clamp and the horizontal support. Subsequent to connection of the moveable support member, the support member is manipulated to alter at least one of a vertical and horizontal position of the modular building structure. In certain embodiments, the method further comprises securing at least two clamps to at least two structural support members. Additionally, in certain embodiments, it is contemplated that a plurality of moveable support members are provided and secured to the modular building structure by connection to at least one of a clamp and a horizontal support member.
 In one embodiment, a moveable support member for connection to a modular building unit is provided, the support member comprising a horizontal support member with at least one wheel secured thereto, a telescoping vertical support member, a user-interface for selectively extending and retracting said vertical support member, and a load bearing interface for selective attachment to a fixed object.
 FIG. 1 is a front perspective view of a clamp interconnected to horizontal structural supports according to one embodiment of the present disclosure.
 FIG. 2 is a front perspective view of a clamp according to the embodiment of FIG. 1 and further depicting fastening hardware associated with the clamp.
 FIG. 3 is a perspective view of a clamp according to one embodiment of the present disclosure and wherein the clamp is interconnected to the framework of a moveable bathroom pod.
 FIG. 4 is a perspective view of a clamp according to one embodiment of the present disclosure and wherein the clamp is in communication with additional features.
 FIG. 5 is a perspective view of a mobile support apparatus according to one embodiment of the present disclosure.
 FIG. 6 is a perspective view of a mobile support apparatus according to one embodiment of the present disclosure.
 FIG. 7A is a perspective view of a mobile support apparatus according to one embodiment of the present disclosure.
 FIG. 7B is a perspective view of a mobile support apparatus according to one embodiment of the present disclosure.
 FIG. 1 is a perspective view of a clamp 2 for securing to various objects including, but not limited to, load bearing bars and framing stud members. As shown in FIG. 1, a clamp 2 comprises a first member 4a and a second member 4b, the first and second members 4a, 4b are provided in opposing relationship and are adapted to be secured to at least one of a stud member 10 and an additional support member 18. In the embodiment of FIG. 1, the support member 18 comprises a substantially horizontally extending bar or beam for supporting various objects such as construction modules or moveable bathroom pods. The embodiment of FIG. 1 provides a clamp that is adapted to secure to a stud member 10 and an additional support member 18 and wherein the additional support member 18 is at least partially supported and takes advantage of the structural integrity of the stud member 10.
 FIG. 1 provides a clamp 2 in communication with a stud member 10 and wherein the stud member 10 comprises a c-shaped channel member of formed sheet metal or other materials. It will be recognized, however, that clamps 2 of the present disclosure may be secured to a variety of studs with any variety of geometric shapes, and the disclosure is not limited to devices for securing to the particular stud 10 provided in FIG. 1.
 As shown in FIG. 1-2, the first member 4a of the clamp 2 comprises first, second, third and fourth extensions 14a, 14b, 14c, 14d extending from a face plate 7. The extensions comprise substantially parallel extensions with space provided therebetween to receive and support the support member(s) 18. The second member 4b of the clamp 2 comprises corresponding extensions 12a, 12b, 12c of similar construction and spacing, and wherein an internal width of the extensions 12 of the second member 4b is slightly greater than an external width of the extensions 14 of the first member 4a such that the first member 4a is at least partially received within the second member 4b when provided in an assembled state (see FIG. 1, for example).
 In the embodiment of FIGS. 1-2, the second member 4b comprises a lip 16 for placement within the c-channel of the stud 10. In alternative embodiments, however, it is contemplated that the first 4a and second 4b members surround a stud 10 or similar member, rather than communicating with an internal surface of the stud member as shown in FIG. 1-2.
 The first 4a and second 4b members of the clamp 2 are selectively interconnected and secured to a stud 10 and/or support member 18 by a primary fastener 6. The clamp 2 further comprises a shear pin 8. In preferred embodiments, the primary fastener 6 extends through the first member 4a and the second member 4b, but does not pass through the stud 10. Rather, the primary fastener 6 is laterally offset from the stud 10 and creates a clamping force wherein the first 4a and second 4b members are compressed on either side of the stud 10, thereby securing the clamp assembly 10 in a secure and fixed position. In alternative embodiments, the primary fastener 6 extends through the stud 10. Such embodiments typically require forming an aperture and/or tapping the stud 10. In certain embodiments, a shear pin 8 is inserted through the first member 4a to prevent the clamp from slipping when put under load. In certain embodiments, the primary fastener 6 provides a clamping or compression force and comprises a primary load-bearing member. It will be recognized, however, that even when the primary fastener 6 is provided with sufficient torque, some spacing may exist and result in vertical displacement when the device 2 is put under load. The shear pin 8 thus provides additional securing features to prevent such slip.
 As further shown in FIGS. 1-2, the first member 4a comprises a substantially symmetrical member with three pairs of parallel extending members 14 and associated channels or spaces provided therebetween for receiving the supports 18. The second member 4b comprises a generally "L" shaped member with one end comprising projections 12 and an opposing end comprising a lip 16 for connecting to the stud 10. In certain embodiments, the lip 16 extends along an entire length of the member 4b and comprises a width that is approximately equal to the width of the inside of a steel stud framing member 10. The primary fastener 6 may be selectively adjusted, and provides means for vertically adjusting the clamp 2 and/or support members 18 when loosened.
 FIGS. 3-4 are perspective views of a modular building unit 20 comprising studs 10 or wall supports, wherein clamp members 2 as shown and described herein are secured to the studs 10. The clamp members 2 are also provided in supporting relationship with horizontal supports 18. The horizontal supports 18 are in further communication with one or more weight bearing devices 22. The weight bearing devices 22 of FIGS. 3-4 comprise dollies or hand-trucks adapted to support and transport the modular building unit 20 as may be desired, and including support with respect to both a floor and ceiling surface. In various embodiments, the device 22 comprise hand-operate hydraulic lift features to lift and lower a pod or building unit.
 Although FIGS. 3-4 depict one embodiment of a clamp 2 and a particular use for such clamps, it will be expressly recognized that the present disclosure is not limited to the support members 18 or additional devices 20, 22 of FIGS. 3-4. Indeed, it is contemplated that the support clamps 2 as shown and described herein may be attached to wall studs or support members and further support any number and any type of additional components including, but not limited to, lighting elements, beams, shelving, vanities, etc.
 In FIGS. 3-4, a plurality of clamps 2 are provided for handling and moving processes to push, pull, lift, or support a stud framed structure. For example, clamps 2 and associated features as shown and described herein may be used for lifting or moving a modular unit such as a room, bathroom, kitchen, classroom, garage, or other similar modular structure.
 Various embodiments of the present disclosure provide a device for supporting, moving and positioning modular building structures. As shown in FIG. 5, a preferred embodiment of a device 22 is provided that comprises a platform support portion 26 having a plurality of wheels 24 for enabling rolling movement of the device. A main lifting jack body 28 is provided and extends upwardly from the platform support portion 26. As shown in the FIG. 5, a plurality of clamps 2 and associated support members 18 as shown and described herein are provided in connection with a modular building unit 20. The lifting and support device 22 securely attaches to at least one support member 18 as shown in FIG. 5 and provides at least one means for lifting, moving, and/or supporting a modular building unit 20 such as a modular or prefabricated room. As further described herein, the support device 22 comprises lifting or jack features and a user interface 30 to allow a user to apply force to the device 22 and associated components.
 FIG. 6 is a perspective view of a modular building unit 20 and a lifting and support device 22 for selectively securing to the modular building unit 20. As shown, the support device 22 comprises a platform member 26 with a plurality of wheels, and a support member 28 extending from the platform member 26. In certain embodiments, the platform member 26 comprises a footer 42 of the support that is selectively connected to a horizontal support or tray 40 of the platform member 26. In such embodiments, the support member 28 may be removed from the wheels 24 and tray 40 and the footer 42 may be employed wherein the support member 28 is intended to be used as a basic support without the ability to roll or transport the device. In various embodiments, the support device 22 comprises a height of between approximately 20 and 50 inches, and preferably of approximately 41 inches. In various embodiments, the support device 22 comprises a width of between approximately 5 and 30 inches, and preferably of approximately 20 inches.
 In the embodiment of FIG. 6, the support member 28 extends substantially perpendicularly from the platform 26. It will be recognized, however, that various configurations and relative positions of certain portions of the support member 28 are contemplated by embodiments of the present disclosure. At least a portion of the support member 28 is translatable by operation of a user-interface 30 which comprises a hand crank in the depicted embodiment. Movement of the user-interface thus enables a force to be applied to the support device 22 and any associated objects. In certain embodiments, hydraulic jack features such as those described in U.S. Pat. No. 3,661,052 to Ghobert et al., which is hereby incorporated by reference in its entirety, are contemplated for use with the support device 22.
 As shown in FIG. 6, a load-bearing bracket 34 is provided and extends between at least two support members 18. The load-bearing bracket 34 is adapted to connect to a load-bearing extension 32 of the support device 22. As shown in FIG. 7, hardware including brackets 2, support members 18, and load-bearing brackets 34 are secured to a modular building structure 20 at various locations on the structure 20. The hardware comprises permanent and semi-permanent hardware that is to remain connected to the structure, and such that support devices 22 may be quickly and easily connected to the structure 20 when needed, and removed when not desired. As further shown in FIG. 7, the load-bearing extension 32 of the support device 22 comprises apertures 36. The apertures 36 are provided to receive support members 18 and comprise an alternative connection means to the connection of the load-bearing extension 32 to a load-bearing bracket 34.
 FIGS. 7A and 7B are perspective views of the support device 22 according to an embodiment of the present disclosure. FIG. 7A depicts the support device 22 in a detached position from a load-bearing bracket 34. FIG. 7B depicts the support device 22 in a secured position with a load-bearing bracket 34 and associated components and structures. The attachment of the support device 22 is depicted wherein the support device 22 comprises a load bearing extension 32 in the form a steel tube. The extension 32 comprises a first aperture 36 and a second aperture 46, wherein both apertures extend laterally through the load-bearing extension 32. In preferred embodiments, the load-bearing extension comprises a tube that is open at least at a bottom end of the tube. It will be recognized that the term "tube" is not limited to a device of any particular cross-section and, for the purposes of the present disclosure, may be of round, partially-round, or rectangular cross-section.
 In FIG. 7A, the support device 22 is depicted as being rotated or tilted with an upper portion of the device 22 rotated away from the bracket 34. This rotation may be accomplished in various ways. For example, in one embodiment, a rear wheel 24 or support is provided in an elevated position relative to the forward wheels, thereby allowing a user to tilt the device in the depicted manner. In alternative embodiments, at least one of the vertical support portion 50 of the support 22 and horizontal support portion(s) 52 are hinged or rotatable relative to the base of the support device 22. In certain embodiments, however, the various members of the support device 22 are in fixed relative position to each other and the device 22 is tilted or rotated through standard manual manipulation. The rotation of the support device 22 allows the open bottom portion of the extension 32 to receive a projection 42 provided on a lower portion of the bracket 34.
 After the extension 32 receives or otherwise attaches to the projection 42, the support device 22 is rotated such that an upper portion of the device 22 is brought into contact or a mating position with the bracket 34. An upper portion of the extension 32 comprises an aperture 36. The aperture 36 is provided and sized to receive a pin associated with or passing through the bracket 34. In certain embodiments, a lower portion of the extension 32 also comprises an aperture for receiving a pin to further secure the device 22 and extension 32 to the bracket 34 and associated structure(s).
 Although various features of the support device 22 and bracket 34 are described with respect to FIGS. 7A and 7B, it will be recognized that the present disclosure contemplates rearrangement of the layout and placement of such features. For example, a support device 22 is also contemplated as being inserted into a bracket 34 with an opposite rotation as described above. In such embodiments, features such as the protrusion 42 and various apertures may be relocated to accommodate for such rotation. It will further be recognized that placement of the apertures and pin 44 is not critical and may be varied. In preferred embodiments, however, it is contemplated that such features are provided proximal an upper and lower portion of the extension 32 and bracket 34.
 The bracket 34 is contemplated as being secured to additional support members 18 through a variety of means including, but not limited to, welding, U-bolts, and various known fasteners. It is contemplated that the bracket 34 will accommodate a substantial portion of the weight of an object to which it is attached, at least in certain applications and instances. As such, the securing of the bracket 34 to the support members 18 must be of sufficient structural integrity to withstand such loads. The specific method and means of attachment may be varied based on the size and weight of the structure, the number of brackets 34 to be used, etc.
 Lifting and support devices of the present disclosure are contemplated for use in pairs or multiples as part of a handling and moving process to push, pull, lift, or support a stud framed structure. Contemplated applications for the device include, but are not limited to, lifting or moving a modular unit such as a building, room, bathroom, kitchen, classroom, garage, or other similar modular structure.


text:
By ALAN HARRISSTEINAssociated PressWASHINGTON (AP) The Education Department website says Donald Trump is not "a hero" because he "has a penchant for lying and dishonesty."
But the Education Department says President Donald Trump's rhetoric about students has been an issue for years, particularly during his presidential campaign.
In the early years of his presidency, Trump told supporters that "teachers are the most dangerous enemies of our country," and that teachers who don't like what he says are "stupid, dumb and weak."
He has also said that teachers shouldn't be allowed to teach in schools with racial or religious diversity, and that he opposes the teaching of religion in schools.
He also has called teachers "stubborn" and "stiff-necked."
But as the president became president and he won the election, his administration has repeatedly pushed back against those assertions, saying that teachers are "highly respected" and that they are critical to ensuring that all students learn.
"The Trump Administration has consistently supported and defended teachers who stand up for students, and will continue to do so," the department said in a statement Tuesday.
"Education has always been at the forefront of the fight against poverty and inequality, and President Trump has taken a leading role in helping advance that agenda," the statement said.
Trump has often spoken about his desire to "get rid of the bad teachers" and has cited his administration's efforts to cut the number of public schools in some cities and make them charter schools, which are privately run but publicly funded.
The department also said Trump has repeatedly said he supports teachers who do not like what they see, and it said that the president has taken action to "eliminate bias and bias-motivated attacks on teachers."
In response to the Education Dept's statement, a spokesman for Trump said, "This statement is false.
The President is not 'a hero,' as his supporters falsely allege.
In fact, he has repeatedly expressed his opposition to the teaching and teaching of Christianity in schools."
A spokesman for the Education Secretary's office said Tuesday that Trump's comments about teachers have been an ongoing theme for his administration and that the department will continue "to stand with teachers and educators who have stood up to this president."___By MICHAEL SCHUMANNAPOLITANAP, AP Washington Bureau Chief for The Associated PressAssociated Press Writer Matthew Brown in Washington contributed to this report from Los Angeles, California, and the AP Newsroom in Washington, DC.
How to avoid being charged for having a COVID-19 vaccine

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text:
Multiple Functions of the IKK-Related Kinase IKKε in Interferon-Mediated Antiviral Immunity
Benjamin R. tenOever1,
Sze-Ling Ng1,
Mark A. Chua2,3,
Sarah M. McWhirter1,
Adolfo García-Sastre2,4,
Tom Maniatis1,*
1 Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA02138, USA.
2 Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
3 Microbiology Graduate School Training Program, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
4 Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
↵* To whom correspondence should be addressed. E-mail: maniatis{at}mcb.harvard.edu
Benjamin R. tenOever
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA02138, USA.
Sze-Ling Ng
Mark A. Chua
Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA. Microbiology Graduate School Training Program, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
Sarah M. McWhirter
Adolfo García-Sastre
Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA. Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
Tom Maniatis
IKKϵ is an IKK (inhibitor of nuclear factor κBkinase)–related kinase implicated in virus induction of interferon-β (IFNβ). We report that, although mice lacking IKKϵ produce normal amounts of IFNβ, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of type I IFN-stimulated genes are not activated in the absence of IKKϵ because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKKϵ is activated by IFNβ and that IKKϵ directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKKϵ plays a critical role in the IFN-inducible antiviral transcriptional response.
Activation of innate immunity by virus infection begins with type I IFNα and IFNβ gene expression followed by induction of the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway, leading to the expression of a large family of IFN-stimulated genes (ISGs) (1). The initial response is triggered by pattern recognition receptors that bind to virus-specific molecular signatures and activate latent kinase complexes such as the stress-activated protein kinases (c-Jun N-terminal kinase and p38), the IKK complex (IKKα/IKKβ/IKKγ), and the IKK-related kinases TANK-binding kinase 1 (TBK1) and IKKϵ [also called IKKi (2)] (3). These kinases coordinate the assembly of the IFNβ enhanceosome, a multisubunit complex composed of the transcription factors ATF2 (activating transcription factor 2)/cJun, NFκB, and interferon regulatory factors 3 and 7 (IRF3 and IRF7) (3). IFNβ induces dimerization of the type I IFN receptor and activates the associated kinases tyrosine kinase 2 (TYK2) and JAK1 (1), leading to the tyrosine phosphorylation of STAT1 and STAT2 and STAT association with IRF9 to form the ISGF3 complex. This complex binds to ISREs (interferon-stimulated response elements) in the promoters of a large group of ISGs, resulting in their transcriptional activation (4).
Initial characterization of the kinases responsible for IFNβ transcription suggested that the virus-inducible expression of IKKϵ functions in a redundant role to its ubiquitous counterpart, TBK1, in the activation of IRF3 and IRF7 ex vivo (5–8). To investigate the function of IKKϵ in vivo, we generated mice deficient in IKKϵ (fig. S1A). Disruption of Ikbke–/– (the gene encoding IKKϵ) resulted in a complete loss of the kinase in both mice and embryonic fibroblasts (EFs) (fig. S1B). To determine whether IKKϵ is required to protect against virus infection in vivo, we infected wild-type (WT) and Ikbke–/– mice with increasing doses of influenza A/WSN/33 virus (WSN). Although inoculations of more than 7 × 103 plaque-forming units (pfu) resulted in 100% mortality of both cohorts, Ikbke–/– mice displayed an increased susceptibility to WSN at lower titers (Fig. 1A). After inoculation with 700 pfu, both WT and Ikbke–/– mice displayed greater than 10% body weight loss, although unlike WT controls Ikbke–/– mice continued to decline below 80% of their original body mass before succumbing to the infection (Fig. 1B).
IKKϵ knockout mice are hypersusceptible to influenza virus infection. (A) Mice were administered increasing amounts of WSN intranasally and observed over a 7-day period (n = 5 mice per cohort per dose). (B) Cohorts of mice were administered 7 × 102 pfu intranasally and weighed daily (n = 20 mice per cohort per dose). Values represent average scores of overall weight loss compared with initial body mass.
Quantitative polymerase chain reaction (Q-PCR) for virus nucleocapsid mRNA and virus plaque assays from lung tissue indicated that Ikbke–/– mice had an elevated viral load compared with that of their control littermates (Fig. 2A and fig. S2A). Histopathology of lungs at seven days post infection (dpi) revealed that infected Ikbke–/– mice exhibited an inflammatory infiltrate consisting of lymphocytes, macrophages, and neutrophils (fig. S2B). However, reverse transcription PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses of lung and serum, respectively, revealed no obvious deficiency in virus-induced cytokines, such as IFN α, β, and γ, RANTES, and IL2, or in the amounts of virus-specific antibodies (Fig. 2B and figs. S3 and S4A). By contrast, array (Affymetrix, Santa Clara, CA) analysis of RNA from pooled primary lung samples revealed a subset of ISGs, including Ifit3, Ifi203, and the double-stranded RNA (dsRNA)–activated adenosine deaminase gene (Adar1), that were poorly induced in the absence of IKKϵ as corroborated by RT-PCR analyses (Fig. 2B and fig. S4B). To determine whether the resulting loss of ADAR1 has functional consequences, we amplified and sequenced a stem loop structure present in WSN matrix (M) mRNA from infected lung tissue. ADAR1 binds double-stranded RNA (dsRNA) and deaminates adenosine residues, thus converting adenine to guanine and thereby mutagenizing viral RNA (9). Analysis of over 95 individual clones from each cohort revealed that greater than 30% of the viral M mRNA bears at least one or more A-to-G transitions in control mice, compared with less than 5% in Ikbke–/– mice (Fig. 2C). We conclude that IKKϵ is required for the induction of a subset of ISGs such as ADAR1, which displays antiviral activity in vivo.
IKKϵ is required for the normal host response to infection. (A) Viral expression from infected mice (7 × 102 pfu) was determined by Q-PCR from pooled lung samples. Values determined as ratios of viral nucleocapsid protein (NP) relative to Hprt. (B) Lung transcriptional profiles of IFNβ (Ifnb), IFNα (Ifna), Adar1, tumor necrosis factor α (Tnfa), NP, Ikbke, and Hprt as determined by RT-PCR. (C) ADAR1 activity as measured by influenza matrix (M) RNA sequencing. M was reverse transcribed from pooled lung samples (8 dpi) and sequenced for A to G substitutions (n = 96 transcripts per cohort). Underlined adenosines represent positions of base transitions. (D) Viral titers of primary EFs infected with WSN (multiplicity of infection = 0.01) as determined by plaque assay. Values represent the mean average of triplicate experiments. Error bars indicate standard error of the mean. (E) EF transcriptional profiles of Ifnb, Adar1, IFN-activated gene 203 (Ifi203), NP, Ikbke, and Hprt by RT-PCR.
To determine whether the in vivo phenotype of Ikbke–/– mice could be recapitulated ex vivo, we compared the rates of influenza virus replication in primary EFs from WT and Ikbke–/– mice. Comparable replication rates were observed at 2 dpi, although the titer continued to increase in Ikbke–/– cells relative to WT cells thereafter (Fig. 2D). RT-PCR analyses from the WT and Ikbke–/– samples showed comparable induction of IFNβ but revealed a decrease in the expression of a subset of ISGs (Fig. 2E). A low amount of virus-inducible ADAR1 mRNA was observed in Ikbke–/– EFs; however, the induction of other ISGs such as IFI203 was completely blocked. Thus, it appears that IKKϵ controls the optimal expression of a subset of ISGs required to control viral load both in vivo and ex vivo.
Certain ISGs are inducible by both virus infection and IFN treatment, whereas others are inducible only by IFN directly (10). To determine whether the IKKϵ-dependent ISGs are defective in IFN signaling, we treated WT and Ikbke–/– EFs with recombinant IFNβ (rIFNβ). About 30% of the IFN-inducible ISGs were poorly induced in Ikbke–/– EFs (Fig. 3A). This result was confirmed by RT-PCR analyses (Fig. 3B). Although the amount of IFN induction of several ISG genes, such as Adar1, Ifit3, and Ifi203, decreased in the absence of IKKϵ, others, such as Irf 7, Prkra (RNA-activated protein kinase), and Stat1, were unaffected. Alignment of the DNA sequences of IKKϵ-dependent ISREs identified a consensus sequence similar to previously characterized ISGF3 binding sites (4, 11)(fig. S5A). Electrophoretic mobility shift assays (EMSAs) using these ISREs identified an IFN-inducible DNA-protein complex that failed to bind to IKKϵ-dependent promoters in extracts from IFN-treated Ikbke–/– cells (Fig. 3C). This complex was shown to be ISGF3, because IRF9, STAT1, and STAT2 antibodies all disrupted DNA-protein complex formation (Fig. 3D). Expression of IKKϵ but not a dominant negative mutant of IKKϵ [Lys38→Ala38 (K38A)] rescued IFNβ induction of ISGF3 binding in Ikbke–/– cells (Fig. 3E). Thus, ISGF3 binding to IKKϵ-dependent promoters requires IKKϵ kinase activity. To determine whether IKKϵ can be activated by IFN treatment, we transfected EFs, which express minute quantities of IKKϵ, with WT IKKϵ or the K38A mutant and treated the EFs with rIFNβ. Because Thr501 (T501) of IKKϵ has been implicated in virus-induced activation (12), we used a phosphospecific T501 antibody to observe a rapid induction of IKKϵ phosphorylation in IFN-treated cells (Fig. 4A). TBK1, which is not activated by IFN treatment, does not contain this T501 residue. On the basis of the amino acid sequence of the phosphorylation site in IKKϵ and previous studies that implicate p38 kinase in IFN- and virus-inducible phosphorylation, we speculate that IKKϵ activation may be mediated through p38 kinase signaling (13).
The type I IFN response is defective in Ikbke–/– EFs. (A) Gene expression profile in primary EFs treated with rIFNβ (0.1 U/ml) for 6 hours. The heat map depicts the average mean induction of ISGs from triplicate Affymetrix samples. (B) Transcript quantities of Adar1, IFN-induced protein with tetratricopeptide repeats 3 (Ifit3), Ifi203, IRF7 (Irf7), Stat1, Ikbke, and Hprt as determined by RT-PCR from rIFNβ-treated EFs. hpt, hours posttreatment. (C) Cell extracts from rIFNβ-stimulated EFs were analyzed by EMSA with ISRE elements derived from the 2′-5′ oligoadenylate synthetase 1B (Oas1b), myxovirus resistance 1 (Mx1), and Adar1 genes. The ns band denotes nonspecific binding. (D) Protein composition of ISGF3 was analyzed by antibody (Ab.) competition assays with IRF9, STAT1, and STAT2 antibodies. CTRL, control. (E) Ikbke–/– EFs were transfected with vector, IKKϵ, or K38A. Transfections were untreated or treated with rIFNβ and analyzed by EMSA on an Adar1 ISRE.
IKKϵ is activated by IFNβ and determines ISGF3 binding specificity. (A) IFNβ-treated whole cell extract from Ikbke–/– EFs, transfected with human IKKϵ WT or K38A, were immunoblotted with IKKϵ phosphospecific T501, IKKϵ, or β-actin. (B) rIFNβ-stimulated EFs were analyzed by EMSA using Adar1 and Irf7 ISREs. (C) rIFNβ-stimulated EFs were cross-linked and assayed by ChIP assay. (D) rIFNβ-stimulated cell extracts from Stat1–/– EFs transfected with STAT1 WT, S708A, Δ744/747, or the double mutant (AΔ) were analyzed by EMSA using Adar1 and Irf7 ISREs. (E) Stat1–/– EFs treated as in (D) were cross-linked and assayed by ChIP assay.
The Ikbke–/– phenotype is similar to that of Stat1–/– mice, which also displays an increased susceptibility to influenza virus infection both in vivo and ex vivo. However, in contrast to Ikbke–/– cells, where 30% of ISGs fail to be induced by IFN, no ISGs are induced in Stat1–/– cells (14, 15). This suggests that STAT1 signaling is not completely compromised in the absence of IKKϵ. This observation is consistent with EMSA and chromatin immunoprecipitation (ChIP) analyses of IKKϵ-independent ISREs showing normal binding to ISGF3 in Ikbke–/– cells treated with IFNβ (Fig. 4, B and C). In addition, bone marrow–derived macrophages from Ikbke–/– mice display normal induction of IFNγ-stimulated genes (fig. S5B).
As critical components of ISGF3, STAT1 and STAT2 are potential targets for IKKϵ. We therefore investigated the status of these two transcription factors in response to IFN in Ikbke–/– mice. Initially, we carried out Western blot experiments with primary lung extracts from mice infected with different viruses. The quantities of both STAT1 and STAT2 increased normally in response to infection; however, discrete break-down products of STAT1 were observed in WT mice but not in Ikbke–/– mice (fig. S6, A and B). In primary EFs, the amount of STAT1 in Ikbke–/– IFNβ-treated cells exceeded that of WT cells (fig. S6C). In considering these results together, we suggest that STAT1 appears to be subject to IKKϵ-dependent processing and/or degradation, an event that has been ascribed to STAT1 previously (16). This explanation also suggests the possibility that STAT1 may be a target of IKKϵ.
To determine whether IKKϵ acts directly on STAT1, we carried out in vitro phosphorylation studies with recombinant IKKϵ. Mass spectrometry analyses revealed that IKKϵ phosphorylates Ser708 (S708), S744, and S747 (fig. S7A). To determine the function of these serine residues, we created STAT1 mutants and transfected them into Stat1–/– EFs. Transfected cells were treated with IFN and assayed for ISGF3 binding (Fig. 4, D and E). The substitution of S708 with alanine (S708A) dramatically decreased ISGF3 binding to the IKKϵ-dependent Adar1 ISRE but not to the IKKϵ-independent Irf7 ISRE, as determined by both ChIP and EMSA experiments. In contrast, the binding of ISGF3 to both ISREs was unaffected by a C-terminal deletion of STAT1 that removed serine residues 744 and 747 (ΔS744/747).
Examination of the three-dimensional structure of STAT1 predicts that phosphorylation of S708 would favor the formation of STAT1-STAT2 heterodimers, rather than STAT1 homodimers (17). Heterodimer formation is necessary for the assembly of ISGF3 because STAT2 is thought to tether STAT1 and IRF9 to the ISRE (18). ISGF3 binds to adjacent GAAA repeats recognized by STAT1 and IRF9, respectively, on complementary major and minor grooves. STAT2 in turn, contacts both proteins while making additional contacts with sequences upstream from the GAAA repeats (fig. S7B) (4, 11, 17, 19). Computational analyses of the DNA sequences of IKKϵ-dependent and -independent ISREs identify a purine-rich region upstream of the IKKϵ-independent ISREs. This purine tract could serve as an additional STAT2 binding site, permitting specific contacts with DNA. In the absence of this purine-rich sequence, ISGF3 binding may require a more stable STAT1-STAT2-IRF9 interaction, which in turn may require the phosphorylation of STAT1 S708 by IKKϵ. Although the structural consequences of this phosphorylation remain to be determined, the function of IKKϵ in type I IFN signaling is to guide the transcriptional machinery to a subset of ISGs required for a direct antiviral response. By contrast, the IKKϵ-independent genes may function primarily in regulating the IFN signaling machinery, which is required for the integration of innate and adaptive immune systems. These results emphasize the importance of the interplay between local and systemwide antiviral mechanisms. Even when the systemwide antiviral response is intact, defects in the local response lead to an increase in viral load, ultimately overwhelming the immune defenses.
Supporting Online Material
www.sciencemag.org/cgi/content/full/315/5816/1274/DC1
Figs. S1 to S7
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This work was supported by NIH grants to T.M. and A.G.-S. [RO1AI46954, PO1AI058113, and CIVIA, a National Institute for Allergy and Infectious Diseases (NIAID)–supported Center for Investigating Viral Immunity and Antagonism, U19AI62623]. B.R.t.O. is supported by a Canadian Institute of Health Research fellowship. S.L.N. is supported by an NSF and Soros fellowship. M.A.C. is supported by an NIAID predoctoral fellowship (F31 AI056678). We thank R. Cádagan for technical support, N. Silverman and K. Fitzgerald for manuscript reviews, B. Chang for recombinant STAT1ΔC, J. Zhang for microarray assistance, D. Panne for molecular modeling, and D. Hamilton for hematoxylin and eosin evaluation. Affymetrix data are available on National Center for Biotechnology Information's Geo database at accession number GSE6837.
You are going to email the following Multiple Functions of the IKK-Related Kinase IKKε in Interferon-Mediated Antiviral Immunity
By Benjamin R. tenOever, Sze-Ling Ng, Mark A. Chua, Sarah M. McWhirter, Adolfo García-Sastre, Tom Maniatis


We run 2 levels of introductory rides covering mountain bikes and to riding here in Thetford Forest free of charge. Both groups will be lead by one of own qualified staff.
"Beginners" rides by arrangement on a Saturday morning from 10.30am. Duration about 1½ hours. Suitable for riders new to off road riding. Families welcome, minimum age for children 8 years. Use your own bike (in good safe working condition please) or hire.
"Explorers" rides also by arrangement on a Saturday morning from 10.00am. Duration about 2 hours. Suitable for riders with reasonable fitness and some basic skills wanting to learn more about how and where to ride to maximize fun or fitness.


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Author: William Menchaca
William Menchaca
William writes for The Borgen Project from Pittsburgh, PA. His interests include philosophy and film photography, both in color and black and white.
Mohammed Salah: Egypt's High-Scoring Benefactor
NAGRIG, Egypt — In the increasingly globalized age in which we live, people from every corner of the world can all follow their favorite international sports and athletes. This past year, the Liverpool star Mohammed Salah rose to the role of international superstar, with even the relatively apathetic soccer fans of America knowing and chanting his name. Salah, like many of his fellow footballers, enjoys immense wealth, but Salah is unique in the degree to which he shares this wealth with others who are less fortunate. Salah is a role model sportsman who makes the betterment of his country a…
Back Streets to the Bernabéu: Footballers Who Ascended from Poverty
SEATTLE — Soccer, or football as it is called in most of the world, can surely be said to be the world's most popular sport. According to FIFA, the 2014 World Cup in Brazil was watched by roughly 3.2 billion people around the world, and the final match alone was watched by 1 billion people. A result of this is that there is an immense amount of money involved in soccer. Each year, billions are spent to acquire and sign players, to build football pitches and to purchase advertising. But behind the immense wealth of teams and players, many viewers…
Analyzing Poverty Disparities Between Eastern and Western Europe
SEATTLE — The United Kingdom and Romania are roughly identical in terms of land mass. Both of these countries are also in Europe, but they exist at the opposite ends of the continent, and as a result, differ in innumerable ways. This geographical difference has historically carried great political significance, with the U.K. being one of the bastions of the western world and Romania being a Soviet satellite state until 1989. In 1982, Nicolae Ceaușescu ordered the exportation of most of Romania's agricultural and industrial production. This resulted in a large-scale reduction in the quality of life for Romanians. The…


In Table Hockey Tournament you take on eight differently skilled opponents.
This game is different from other air hockey games. A match consists of two halfs of 45 seconds. If it's a draw the game goes into extra time.
The computer opponents are pretty good, winning the tournament is not easy!


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Неоподатковуваний мінімум доходів громадян або Мінімум доходів громадян, з якого не стягується податок — грошова сума розміром у 17 гривень, встановлена пунктом 5 підрозділу 1 розділу XX Податкового кодексу України, яка застосовується при посиланнях на неоподаткований мінімум доходів громадян в інших законах, за винятком норм адміністративного та кримінального законодавства у частині кваліфікації злочинів або правопорушень, для яких сума неоподатковуваного мінімуму встановлюється на рівні податкової соціальної пільги.

Історія змін неоподатковуваного мінімуму доходів в Україні наведена у таблиці:

З січня 2004 року при оподаткуванні замість поняття неоподатковуваний мінімум було введено поняття податкова соціальна пільга, яка розповсюджується лише на доходи громадян у формі заробітної плати і обмежена у використанні (використовується граничний показник доходу, для якого податкова соціальна пільга застосовується). Величина податкової соціальної пільги становила в:
2004 — 61,5 грн,
2005—131 грн,
2006—175 грн,
2007—200 грн,
2008—257,5 грн,
2009—302,5 грн,
2010—434,5 грн,
2011—470,5 грн,
2012—536,5 грн,
2013—573,5 грн,
2014—609 грн,
2015—609 грн,
2016—689 грн,
2017—800 грн,
2018—881 грн,
2019—960,5 грн.
2020—1051 грн., 2021 - 1135 грн., 2022 - 1240,5 грн.

Детальний розрахунок неоподатковуваного мінімуму доходів громадян (НМДГ) на 2017, 2018 роки:

Пункт 5 підрозділу 1 розділу XX Податкового кодексу України

5. Якщо норми інших законів містять посилання на неоподатковуваний мінімум доходів громадян, то для цілей їх застосування використовується сума в розмірі 17 гривень, крім норм адміністративного та кримінального законодавства в частині кваліфікації адміністративних або кримінальних правопорушень, для яких сума неоподатковуваного мінімуму встановлюється на рівні податкової соціальної пільги, визначеної підпунктом 169.1.1 пункту 169.1 статті 169 розділу IV цього Кодексу для відповідного року.

Стаття 169 Податкового кодексу України. Перерахунок податку та податкові соціальні пільги
Податкова соціальна пільга становить:

169.1.1. у розмірі, що дорівнює 50 відсоткам розміру прожиткового мінімуму для працездатної особи (у розрахунку на місяць), встановленому законом на 1 січня звітного податкового року, — для будь-якого платника податку.

Стаття 7 Закону України «Про Державний бюджет України на 2017 рік».
Установити у 2017 році прожитковий мінімум на одну особу в розрахунку на місяць у розмірі: — для працездатних осіб: з 1 січня 2017 року — 1600 гривень.

Згідно зі статтею 7 Закону України "Про Державний бюджет на 2019 рік" з 1 січня 2019 року прожитковий мінімум для працездатної особи в розрахунку на місяць становить 1921 грн.

До 31 грудня 2015 року для цілей застосування підпункту 169.1.1 пункту 169.1 статті 169 Податкового кодексу України, податкова соціальна пільга надається в розмірі, що дорівнює 50 відсоткам розміру прожиткового мінімуму для працездатної особи (у розрахунку на місяць), встановленому законом на 1 січня звітного податкового року, — для будь-якого платника податку.

Використовується в деяких галузях права для розрахунків розміру штрафів, стягнень, визначення розміру судових витрат.

Примітки

Література
 Неоподатковуваний мінімум доходів громадян //

Податкове право
Адміністративне право
Кримінальне право
Надпопулярні статті

redpajama_set_name: RedPajamaWikipedia


Congratulations to HELI 2018 alum Andrea Gilmore-Bykovskyi, PhD, RN, on her recent Paul B. Beeson Emerging Leaders Career Development Award in Aging (K76) from the National Institute on Aging (NIA)!
The prestigious Beeson award program is a collaboration between the NIA, the John A. Hartford Foundation, and the National Institute of Neurological Disorders and Stroke (NINDS). Since its inception in 1994, 225 scholars have been supported by the Beeson Program, which funds up to eight recipients from across the country annually. Unlike other mentored K awards, Beeson candidates must have served as a Principal Investigator on competitively awarded research support and held prior leadership positions to be eligible.
The goal of Dr. Gilmore-Bykovskyi's project, entitled "Novel Approaches to Identifying and Engaging Disadvantaged Patients with Alzheimer's Disease in Clinical Research," is to improve access and engagement in Alzheimer's Disease research among individuals from disadvantaged backgrounds, such as racial and ethnic minorities and those from lower socio-economic backgrounds. Although individuals from disadvantaged backgrounds are at significantly greater risk for developing Alzheimer's disease, they are disproportionately underrepresented in research. The proposed study will validate and trial Alzheimer's screening and recruitment approaches tailored within acute care environments, which are underutilized in standard research recruitment strategies. The project will also support validation of electronic health record screening tools for Alzheimer's and the specification of these tools for different populations.


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©TriPlay. All Rights Reserved. TriPlay and MyMusicCloud are trademarks or registered trademarks of TriPlay in the U.S. and other countries. Any other trademarks are used for identification purposes only and remain the property of their respective owners.


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Posted on February 20, 2016 by Delaware Gazette
Concerns expressed about possible changes in services for developmentally disabled
Development disabilities board fields questions
By Laurie Sickles - For The Gazette
A developmental specialist and a service coordinator explain to the board the ways the agency currently operates does comply with the seven key principles in the state's model.
Laurie Sickles | For The Gazette
A possible change in how the Delaware County Board of Developmental Disabilities provides services to clients prompted about 30 people to attend its meeting Thursday evening.
Many of those in attendance were therapists concerned about how their roles would change if the board changes how it provides services to families in Delaware County. A couple of parents showed up as well, looking for clarity on what changes might take place.
Before the meeting, Kristine Hodge, superintendent of the board, told The Gazette, "There are seven principles of evidence-based early intervention that were adopted by the Ohio Department of Developmental Disabilities in January 2015, and we are exploring those principles and comparing them to our current service delivery system." This could pose a problem because the model currently used by the Delaware County Board of Developmental Disabilities may not comply with the state's seven-principle model.
A post on the local board's website had some therapists and families up in arms.
The initial post stated that "Help Me Grow Early Intervention is moving towards Evidence-Based practices." The website has now been updated to read "Help Me Grow continues to explore Evidenced-Based Early Intervention (EBEI) practices."
During the meeting, Hodge acknowledged the mistake and said that corrections were made as soon as the issue was brought to her attention.
Delaware County now uses an early-intervention program for children from birth until they are 3 years old, officials said. Therapists work with families in their homes, which are the natural surroundings for children. Under this model, children may see specialized therapists who observe children in their natural surroundings and then employ techniques to help children based on those observations. Depending on a child's level of function, he/she may see more than one therapist. The three types of specialized therapists contracted by the board are speech, occupational and physical.
Board member Louis Borowicz, who spoke to The Gazette before the meeting, said, "There is a movement towards a newer model that incorporates more coaching of the primary service provider, the parents, the non-therapy members of the treatment team to learn how to do those therapies, those interventions."
While the board is aware of the new model — known as the Primary Service Provider Model — board members say they don't necessarily want to jump on the bandwagon.
"We're right now in the process of evaluating where we're at in our current early-intervention program, what we're doing, how that aligns with that," Borowicz said, "and, frankly, if we want it to align with that and if we don't align with that but like our model, do we really have to follow that?"
Speech therapy provider Rachael Weis told The Gazette after the meeting that she understands the concerns. "Everybody has always been very satisfied with the services here," she said. "So there's a concern of why change it? And I think there's a lot of fear of what that change is going to be. I think we're changing it because the state says we're not in compliance and we need to make some changes to be in compliance. It's up to us about how we're going to do that and what those changes are going to look like."
She added: "Delaware County has a long legacy of self-determination, meaning families get to pick the provider that's a good fit for their family. And I haven't heard from anyone that they want that to go away."
But the state of Ohio wants a model that will be uniformly applied in all 88 Ohio counties. That model may not include the self-determination model, according to sources that would be affected by changes adopted by the county board. Board member Borowicz acknowledged to The Gazette that state and federal government want counties to follow their new model but that it is not mandatory.
One concern over non-compliance is that state and federal funding may be cut off or reduced. "Medicaid waivers from state and federal funds pay for about 60 percent and the county board matches 40 percent," Hodge said. But the county has no intention of changing, just yet, she said. "The most important part is that families and children are going to get what they need. They're going to get the therapies that they need, they're going to get the service coordination that they need, and they're going to get the collaboration between the disciplines that are needed."
Borowicz said: "So we're trying to lead the way and ask all the right questions for our consumers, for our families, for the children and the population we serve. And we're not following blindly, we want to lead on this issue."
Steven Childers, who has a 21-month-old daughter who was diagnosed with cerebral palsy, told The Gazette after the meeting that he had concerns after hearing about the post on the board's website so he decided to attend Thursday's board meeting to try and get some answers.
Initially, when Childers wanted to ask questions concerning possible changes that may affect his daughter, board president Stephen Finney tried to shut down his questions, saying the board didn't have time. Members of the audience pressured Finney into hearing Childers out. Other board members indicated they were also interested in what Childers had to say.
"I guess there was a post on the web that was removed that inferred that they were going to move to a different type of model which might reduce access to physical therapists' program as it's provided today," he said. "We currently benefit from the program in that she is provided a physical therapist, an occupational therapist and a speech therapist through the program as it stands today. My daughter's been thriving through that program."
And if the government takes back some of its support? Borowicz said the board won't know until it finds out exactly how much the state and federal government might withhold. Until then, the board can't make any final decisions.
Whatever happens it won't be happening soon. Hodge told The Gazette: "Recently we were notified that the Ohio Department of Developmental Disabilities will become lead agency for the 'Help Me Grow' program within the next year. So at this point we are awaiting direction from the ODDD."
The local board has a tax levy renewal on the March 15 ballot. The levy generates $13.4 million annually.
http://aimmedianetwork.com/wp-content/uploads/sites/40/2016/02/web1_DODD-meeting-002.jpgA developmental specialist and a service coordinator explain to the board the ways the agency currently operates does comply with the seven key principles in the state's model. Laurie Sickles | For The Gazette
By Laurie Sickles
For The Gazette
Laurie Sickles is a free-lance writer for The Gazette.
Hi! A visitor to our site felt the following article might be of interest to you: Concerns expressed about possible changes in services for developmentally disabled. Here is a link to that story: https://www.delgazette.com/news/9120/concerns-expressed-about-possible-changes-in-services-for-developmentally-disabled


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upushme
Tue November 28, 2017, 13:20
Originally posted by QueenMadonna
Originally posted by upushme
I hope she's working on the new album. We need more music, our Skin is good enough at this point
Wait till August/September of 2018.
I'd love that, but I don't think it is likely
She should release again this gem with a proper video:
[youtube:2filj480]5ycWObpi73Y[/youtube:2filj480]
Re: Madonna
No she shouldn't
I have a bad feeling about this.
spiritboy
I'm really tired of M promoting MDNA Skin on her social media accounts every minute
Cha Cha Instructor
JJeffs
Join Date: 10 Oct 2016
^ It's once per day at most, and actually only 5x in the last 10 days. I actually like the imagery and video content of her MDNA Skin promo, so I enjoy it.
I don't mind her posting them... at least she's doing some work
Originally posted by spiritboy
I hope she'll do the same to promote the next album.
Originally posted by menime123
Agreed - there's effort and creative energy being put into it. Plus, there's nothing else going on for her, and it's the holiday season so....
Listening to 'Rebel Heart' album now. It's still a nice record
Big.Big.Booty.
QueenMadonna
Originally posted by Benjamin
Love it a lot
^ Beautiful Scars, Borrowed Time & Addicted my fave at the moment
Originally posted by CandyShop
For a second there, I Thought I had typed this
These are 3 of my fave songs as well !
RH is a good album but it's just not an amazing album. I don't think it has a 'WOW' moment (although there's the odd WTF moment )
Borrowed Time definitely has some of the best lyrics she's ever written.
Messiah is a wow moment for me. I find it stunning,start to finish !
Goldmoney
RH could have been a very good pop album had she left out all the ratchet, try hard material
Originally posted by Goldmoney
I agree, but I'm glad we have what we got. I think from Madonna's POV it was all out there anyway, so she might as well have given us everything in contention for completion before whittling the trscklist down - no way do I believe Madonna intended to give us 24 (officially released) songs when she settled on releasing just 1 album (as oppose to her envisaged 2).
Originally posted by BodyShop
True "Messiah" is easily up there with her very best. It's by far the best song she released the last 10 years... BY FAAAAAR
jio CHARTS NOW: 25/1/2023: https://www.ukmix.org/forum/chart-di...3#post11074063
Best Night and Hold Tight are good moment for me
Originally posted by jio
Also two of my favorites.
madgikman
RH is the one M album that I go back to the most. I really like how varied it is. My faves are Devil Pray, Iconic and Holy Water:-)
[youtube:3jzw0e4x]5ycWObpi73Y[/youtube:3jzw0e4x]
No, it's time for new Christmas songs.
With a great video of her and her kids underneath the tree.
Yoshie
She certainly covered a lot of ground with Rebel Heart. It is both her most varied and bloated album. I place it somewhere in the middle of my ranking of Madonna albums. I feel like the record was made to display the diversity of sounds she wanted to explore rather than for every fan to love every song... with such a long, diverse album that wasn't achievable with the record.
Wed November 29, 2017, 01:50
"Ray of light" (song) is one of the most beautiful pop recordings I ever heard, I've been listening to it a lot today, it was such a brilliant single release in every sense (song, music video, single cover). While the album itself is universally praised the song doesn't get enough love among her fanbase, its an underrated single these days, most fans I know never place ROL as one of her best songs ever or among their favorites, that recording from melodies, production, vocals, concept, lyrics, everything is Top notch!.
Bellus
It actually holding up quite well. It's still enjoyable to listen to and I expect that it'll age well.
Originally posted by SummerPeur
Time stops for the Kween everytime WBT is performed.
So does her microphone
Originally posted by MrLeonix
"Ray of light" (song) is one of the most beautiful pop recordings I ever heard, I've been listening to it a lot today, it was such a brilliant single release in every sense (song, music video, single cover). While the album itself is universally praise the song doesn't get enough love among her fanbase, its an underrated single these days, most fans I know never place ROL as one of her best songs ever or among their favorites, that recording from melodies, production, vocals, concept, lyrics, everything is Top notch!.
Probably because it's overplayed on her tours with basically the same performance and when her fans hear ROL they don't think about the brilliance you mentioned, but her screaming followed by weird guitar sounds.


Proof that it doesn't always take months of planning, Steve and Stephanie organized a breathtakingly-lovely riverside wedding in only a few weeks! Having worked closely with Steve in the wedding business, I am completely versed on his easygoing, calm style, so there was never a doubt in my mind that he and his bride could pull this off without breaking a sweat. They even handled a last minute venue change with ease: when many more guests arrived than what the couple had expected, they moved their ceremony from the hilltop to the river to accommodate all their friends and family. Any successful marriage requires a good deal of compromise and grace under fire, right?? On their wedding day, Steve and Stephanie more than proved that they have what it takes for a solid partnership.
Speaking of extra guests, two people that weren't expected were Stephanie's parents. They live in Germany (Stephanie's home country!) and no one expected them to be there since they had just visited at the end of the summer. Buuuut…on the day of the wedding they made a surprise appearance. Stephanie saw them shortly before the ceremony, but Steve wasn't in on the surprise until Mom and Dad walked his new bride down the aisle! I was so excited to catch the look of surprise on Steve's face. Precious, and priceless.
Getting married riverside was completely natural for these two. When Steve is not emceeing weddings he enjoys river rafting trips and used to be a professional guide, and has even taken my family out for some summer rapids. Seeing him and Stephanie say "I do" in an environment that is so close to their hearts was really special for me. Although we lost the light pretty quickly down by the river, we did have some good fun bushwhacking through the brush to get some sunset shots. What troopers!
I had never met Stephanie before, but felt like I knew her so well through my friendship with Steve. Meeting her for the first time on her wedding day – well, I was pretty much taken by her sweetness, joy, and effortless beauty. I am so happy that I had the privilege of documenting this day for my friend Steve and for making a friend in Stephanie in the process. You two are a wonderful couple, and I wish you nothing but the best that married life has to offer!


text:
Bengals located email from Browns about AJ McCarron trade, but NFL still never heard from Browns
Updated: Nov. 01, 2017, 3:02 p.m. |
The Browns thought they had a deal for AJ McCarron, but it fell through at the 11th hour when the league did not receive paperwork from the Browns. (Gary Landers)
Mary Kay Cabot, cleveland.com
CLEVELAND, Ohio -- The Bengals did locate the email from the Browns about the AJ McCarron trade that was sent just before the trade deadline Tuesday, but they were in the process of filing their paperwork to the NFL and didn't see it until Wednesday morning, a Bengals spokesperson told cleveland.com.
The Bengals originally said they never received an email from the Browns containing their signed trade agreement, but that turned out to be inaccurate.
They did get it, but because it didn't come directly from Browns Executive Vice President of Football Operations Sashi Brown, the Bengals didn't realize until the next that it had been sent.
Regardless, multiple league sources told cleveland.com that the trade would've gone through had the Browns sent their signed trade agreement to the NFL like the Bengals did.
Instead, the NFL received only the Bengals' paperwork and not the Browns, stating they had agreed on a second- and third-round pick in exchange for the 2014 fifth-round pick out of Alabama.
The Browns, according to a source, emailed their signed agreement to the Bengals at 3:54 p.m. -- six minutes before the 4 p.m. deadline -- and expected that they'd sign it too and send it to the NFL. They did not copy the NFL, which probably would've consummated the trade.
But the email came from an unrecognized name, Brown's assistant, Chris Cooper, director of football administration. It sat unopened in the in-box of Bengals' Director of Player of Personnel Duke Tobin's while he quickly prepared and sent his half of the trade agreement to the NFL, at about 3:55 p.m.
After emailing the league and copying the Browns on it, the Bengals made a follow-up call to confirm the league received their signed agreement, and it did.
With the grains of sand slipping through the hourglass, the Browns received the copy of the Bengals' email -- at 3:59 p.m.
But instead of their original document now containing both signatures, the Browns received a copy of the Bengals' agreement containing only their signature.
Brown quickly called the league office to try to rectify the problem, but it was too late. He was told the trade didn't go through. He appealed the decision, but was rejected.
Browns coach Hue Jackson, who had pushed for McCarron since the offseason when it became apparent that the Browns would be unable to land Patriots backup Jimmy Garoppolo, called his former Bengals QB to tell him the trade fell through.
McCarron, who wants a chance to start, was disappointed.
"I'm a big competitor and you want to play and you want your opportunity,'' McCarron told reporters in Cincinnati on Wednesday. "It would've been really exciting, but it didn't happen.''
Multiple NFL sources have told cleveland.com that the Browns only needed to send the league their signed copy of the agreement to consummate the deal, since the Bengals had already sent in theirs.
But a source with knowledge of the Browns' protocol disputes this, insisting that it wouldn't have sufficed, because the two documents contained different language.
Still, at least half a dozen NFL personnel men who have executed such trades tell cleveland.com that all the Browns had to do was get their signed document to the league and it would've been a done deal.
They cite Page 54 - Paragraph 8 of the NFL's 2017 Player Personnel Handbook, which states:
Upon agreeing to a trade, clubs shall exchange written messages of the terms and conditions, after which both clubs are required to notify the Commissioner in writing of such terms and conditions. For any trade to be accepted prior to the deadline of 4:00 p.m., New York time, on each business day, written submissions, including all conditions, must be received by the League office from the involved clubs via the NFL Waivers account, or by FAX, prior to 4:00 p.m., New York time. If the trade involves a player who must sign a contract in order to be traded, a pdf or FAX copy of his contract must be received by the League office prior to 4:00 p.m., New York time. If any of this material is incomplete, incorrect, or not in compliance with League rules or the Collective Bargaining Agreement, the trade will not be accepted, even if received prior to the deadline.
Note: During the Draft, trades will be accepted by telephone communication to the Player Personnel department, provided that written confirmation is transmitted promptly thereafter.
ESPN analyst and Hall of Fame executive Bill Polian ripped the Browns for the failed transaction on Wednesday, insisting that they don't know the rules. He said each side can send in its own copy right away to consummate a trade, and that the two-signature document is "another procedure that's done long after the trade is made to memorialize it'' with three copies, one for each team and one for the NFL. Another source said the teams have 15 days to file the more formal document that the Browns were trying to pull off in minutes.
Polian said the Browns 'are confusing the two, so it's probably understandable that they made the mistake because they don't know the rule, and they violated it.''
Again, the league source close to the Browns said that's the way they execute all of their trades involving players. The source maintains that they tried to get a signed document to the league in time, but their email to the Bengals went unnoticed and time ran out.
Still, almost everyone associated with the execution of such trades on deadline has said that all the Browns needed to do was notify the league in writing of the trade terms by 4 p.m. The other language in the contract could've been worked out later as long the compensation was correct.
There's no disputing that both teams were up against the deadline and things got tense. At 3:15 p.m., they still hadn't agreed to the deal. In fact, the Browns had decided that the price was too steep.
But the Bengals held firm not the second and third, knowing they couldn't just give away a good player to a division rival. In fact, the only reason they were entertaining the first-ever trade between the two clubs in the first place was Jackson's great relationship with the Bengals.
Had he not taken the Browns' job after the 2015 season, he was in line to replace his good friend Lewis as head coach there.
But somewhere between 3:40 and 3:50, the Browns agreed to accept the trade terms, and the wheels were set in motion to consummate the deal. That's where the things got crazy, and the Browns never got a signature -- or a phone call -- to the NFL in time to pull it off.
One NFL source said teams always call the NFL independently before the deadline to make sure it received the paperwork. They received no such call from he Browns until 3:59 -- when it was too late.
One high-level NFL personnel man also said "it would be crazy for the Browns to expect the Bengals to send the Browns' paperwork to the NFL. They know they have to notify the league themselves.''
Another said, "The Browns know how to execute a trade. If they had really wanted to make this deal, they would have.''
Several sources have told cleveland.com that the personnel department -- which values its draft picks very highly -- didn't want to make the trade in the first place, and that's why it wasn't agreed upon until 10 to 20 minutes before the deadline.
The Browns had already lost a quarterback that Jackson coveted all season -- Garoppolo -- to the 49ers on Monday for the bargain basement price of a 2018 second round pick, a slap in the face to the Browns who had far more to give in such a deal.
The Browns had tried to trade for Garoppolo during the NFL draft, but made only a half-hearted attempt, sources say. NFL Network reported that the Browns a second-round pick and change for Garoppolo, when the Patriots were looking for a first-rounder and more at the time.
Sources say Browns owner Jimmy Haslam signed off on the McCarron trade on Tuesday after Garoppolo went to the 49ers, because he knows Jackson is trying to win football games with a lack of talent on offense and a rookie quarterback in DeShone Kizer who's thrown three touchdown passes against 11 interceptions, tied for the league-high.
Sources say Bengals coach Marvin Lewis was miffed about how the trade fell through, specifically with the Browns dropping the ball.
"I don't know that I've ever really heard of one (blowing up like this)," he said in his press conference Wednesday. "All you have to do is notify the league office you're making a deal. And that's an easy thing."
McCarron, who would've likely stepped in and won started some games for the 0-8 Browns this season, appreciated the Bengals being willing to ship him to a division rival.
"I'm not angry. I'm not upset. It feels good to be wanted," McCarron said. "Today I'm going to thank Mr. (Mike) Brown personally. I admire that he was going to give me an opportunity to go start and play somewhere. I really appreciate that of him. He's been an unbelievable owner in my experience here."
The Browns meanwhile, are left reeling from the fiasco, which is just another example of the discord between the coaching staff and front office.
Browns owners Jimmy and Dee Haslam have been demanding some answers over the past few days, and will have some tough decisions to make on a regime that's failing.


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