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The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling
Get PDFFKBP52 and β-catenin have emerged in recent years as attractive targets for prostate cancer treatment. β-catenin interacts directly with the androgen receptor (AR) and has been characterized as a co-activator of AR-mediated transcription. FKBP52 is a positive regulator of AR in cellular and whole animal models and is required for the development of androgendependent tissues. We previously characterized an AR inhibitor termed MJC13 that putatively targets the AR BF3 surface to specifically inhibit FKBP52-regulated AR signaling. Predictive modeling suggests that β-catenin interacts with the AR hormone binding domain on a surface that overlaps with BF3. Here we demonstrate that FKBP52 and β-catenin interact directly in vitro and act in concert to promote a synergistic up-regulation of both hormone-independent and -dependent AR signaling. Our data demonstrate that FKBP52 promotes β-catenin interaction with AR and is required for β-catenin co-activation of AR activity in prostate cancer cells. MJC13 effectively blocks β-catenin interaction with the AR LBD and the synergistic up-regulation of AR by FKBP52 and β-catenin. Our data suggest that co-regulation of AR by FKBP52 and β-catenin does not require FKBP52 PPIase catalytic activity, nor FKBP52 binding to Hsp90. However, the FKBP52 proline-rich loop that overhangs the PPIase pocket is critical for synerg
The Introductory Physics Lab as a Consulting Firm
Get PDFMany students in our calculus-based introductory physics courses plan to pursue careers in high technology industries. The laboratory curriculum entitled Mechanics, Inc. is designed to resemble the typical work environment of an R&D consulting firm. Upon entering, students begin a series of training activities focused on applications of physics topics to situations of interest to ersatz clients. These physics topics are chosen to complement the usual sequence encountered in the classroom. Inspiration for the instructional design of the curriculum comes from Modeling Instruction, a well-known approach disseminated to science teachers in workshops across the country, and from Cognitive Apprenticeship, which is less well known in physics pedagogy but widely used in language instruction and other areas. Students are coached and guided in the development of laboratory skills, application of physics concepts, and in the communication of laboratory work in a formal report. During the training activities, components of that formal laboratory report are added sequentially; the initial emphasis is on readable figures and captions. After several activities that each focus on another section of a conventional report, the final training activity brings all sections together in a full, formal laboratory report. With a few weeks remaining in the course, the students apply what they have learned in training activities to tasks needed by another ersatz client. These present somewhat ambiguous problems that students must first clarify. Their responses to the client’s challenges are presented in a formal laboratory report
Variations of Local Piezoelectricity in Multiferroic CoFe2O4–Pb(Zr0.3,Ti0.7)O3 Composite Nanofibers
No full textMultiferroic CoFe2O4–Pb(Zr0.3,Ti0.7)O3 (CFO–PZT) nanofibers (NFs) were fabricated by the electrospinning from a mixture of PVP/ions precursor solution. CFO and PZT nanocrystals random stacked along the NF. Microstructure observations reveal that the PZT nanocrystal is surrounded by CFO nanocrystals and vice versa, which result in the disconnected spatial distribution of the piezoelectric coefficient (d33). Ferromagnetism and ferroelectricity are demonstrated by magnetic hysteresis loops and amplitude–voltage butterfly curve, respectively. Local piezoelectricity cannot represents the whole piezoelectricity of a multiferroic composite NF because it changes near the ferromagnetic crystals. This performance allows further understanding of the strain transformation between each phase in multiferroic composite NFs
2015 Self-Study
No full textThis document is intended to fulfill the self-study requirement associated with ABET’s 2015 accreditation review of the Mechanical Engineering program at Kettering University
Method and Apparatus for Diagnosing and Assessing Centralized Pain
Get PDFMethods for central pain diagnosis and assessment, symptom severity prediction, and therapeutic intervention effect determination. The diagnosis and assessment method includes a statistical comparison between a subject\u27s quantitative brain function assessment and either a database of quantitative assessments of brain functions of healthy individuals, or a database of quantitative assessments of brain functions of individuals known to have been suffering from chronic pain as a result of the abnormal brain function condition. Diagnosis and assessment may be accomplished using a neuroimaging device to sense and generate images representing central nervous system function, using a sensory stimulation device to stimulate brain activities associated with central sensitivity, and using a computing device to command the sensory stimulation device and neuroimaging device to test for the presence of central pain
