Coordinating Tissue Regeneration Through Transforming Growth Factorâ β Activated Kinase 1 Inactivation and Reactivation

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factorâ β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment (â drug onâ ), the impact of drug withdrawal (â drug offâ ) implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dualâ inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment (â drug onâ ) and subsequent withdrawal (â drug offâ ) through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the â drug onâ (Creâ mediated inactivation) and â drug offâ (Flpâ mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766â 778Manipulating transforming growth factor βâ activated kinase 1 for cell and scaffold free tissue regeneration using a dualâ inducible Combinational Sequential Inversion Engineering mouse model.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/1/stem2991_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/2/stem2991.pd

Fritz Leiber Remembered, 1910-1992: Grand Master of Science Fiction and Fantasy

1 Electronic records. 1 DVD Disc. Copied to ISO, MPG, MP4. 3.94 GB, 4227296627 bytes. 00:54:37. 1 scan of DVD cover tif, pdf; thumbnail of cover. 1 branding sheet. 34.6 GB (37,163,689,146 bytes).Fritz Leiber Remembered, 1910-1992: Grand Master of Science Fiction and Fantasy. Video documentary, 1992. Produced by Familiar Productions, San Francisco (Calif.). DVD Rip (originally on VHS), 352 x 240 MPEG-1/2 29.97 FPS. Converted to H.264 MP4. Available on YouTube at https://youtu.be/uc-z-s5Ymn4 Fritz Leiber's brilliant 50 year career as a writer of science fiction and fantasy was marked by over 30 awards. He earned seven Hugos, four Nebulas, and numerous Grand Master of Life Achievement awards. His novels and stories influenced and impressed many other writers while captivating readers for decades. This hour long video is an informal tribute to a talented writer, good friend, and perfect gentleman - Fritz Leiber, Jr. The program includes intimate interviews with Fritz, his fellow writers, friends, and family. Video footage includes book signings, panels, and participation in a Heathen Sumbel. Featured are statements by Fritz Leiber, Justin Leiber, Margo Skinner Leiber, Harlan Ellison, Judith Merrill, Poul Anderson, Greg Bear, Susan Dexter, Megan Lindholm, S.P. Somtow, and others. This hour long video is our informal tribute to a talented writer, good friend, and perfect gentleman - Fritz Leiber, Jr. The program includes intimate interviews with Fritz, his fellow writers, friends, and family. We feature statements by Fritz Leiber, Justin Leiber, Margo Skinner Leiber, Harlan Ellison, Judith Merril, Poul Anderson, Greg Bear, Susan Dexter, Megan Lindholm, S.P. Somtow, and others. Produced by Greg Harder; Computer Graphics by Owen Rowley; Music by Robyn North Star; Cover Design by Prudence Priest; This digital asset has been authorized by Prudence Priest to the Valdosta State University, Archives and Special Collections to be part of the Prudence Priest Collection of the New Age Movements, Occultism, and Spiritualism Research Library

Relevant restricted quantification

The paper reviews a number of approaches for handling restricted quantification in relevant logic, and proposes a novel one. This proceeds by introducing a novel kind of enthymematic conditional.</p