Characterization of a far-red analog of ghrelin for imaging GHS-R in P19-derived cardiomyocytes.

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as measured in HEK293 cells overexpressing GHS-R1a was within an order of magnitude of that of fluorescein-ghrelin and native human ghrelin, while the des-acyl Cy5-ghrelin did not bind GHS-R1a. Live cell imaging in HEK293/GHS-R1a cells showed cell surface labeling that was displaced by excess ghrelin. Interestingly, Cy5-ghrelin, but not the des-acyl analog, showed concentration-dependent binding in mouse heart tissue sections. We then used Cy5-ghrelin to track GHS-R expression in P19-derived cardiomyocytes. Live cell imaging at different time points after DMSO-induced differentiation showed that GHS-R expression preceded that of the differentiation marker aMHC and tracked with the contractility marker SERCA 2a. Our far-red analog of ghrelin adds to the tools we are developing to map GHS-R in developing and diseased cardiac tissues

Entry, Descent and Landing Systems Analysis Study: Phase 1 Report

NASA senior management commissioned the Entry, Descent and Landing Systems Analysis (EDL-SA) Study in 2008 to identify and roadmap the Entry, Descent and Landing (EDL) technology investments that the agency needed to make in order to successfully land large payloads at Mars for both robotic and human-scale missions. This paper summarizes the motivation, approach and top-level results from Year 1 of the study, which focused on landing 10-50 mt on Mars, but also included a trade study of the best advanced parachute design for increasing the landed payloads within the EDL architecture of the Mars Science Laboratory (MSL) missio

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Fab Lab: Creating Design-to-Prototype Learning Modules at the Museum of Science and Industry (sequence unknown), IPRO 333 - Deliverables: IPRO 333 IPRO Day Presentation F09

The primary objective of IPRO 333 is to partner the knowledge and ideas of young engineers, architects, and scientists at IIT with the resources of the Museum of Science and Industry (MSI) in Chicago. This partnership endeavors to help the museum's Fabrication Laboratory (Fab Lab) maximize its potential as a resource for museum guests, young and old, as well as for IIT students, staff, and faculty.Sponsorship: Museum of Science and Industry. Steven Willis- Director, Fabrication LabDeliverables for IPRO 333: Fab Lab: Creating Design-to-Prototype Learning Modules at the Museum of Science and Industry for the fall 2009 semeste

Fab Lab (Semester Unknown) IPRO 333: FabLabIPRO333ProjectPlanF09

Fabrication Laboratories, or Fab Labs, were started as a community outreach program by the Massachusetts Institute of Technology and provide digital fabrication tools for rapid prototyping to the general public. The Museum of Science and Industry has partnered with this IPRO to further develop the Fab Lab at their site. IPRO 333 currently works with the administration in the Fab lab of MSI to design materials and activities for increasing the use of the laboratory. IPRO 333 aims to broaden the possible uses of the lab, promote membership at the museum, and increasing participation by the community in science and technology programs at the museum.Sponsorship: Fabrication Laboratories, or Fab LabsDeliverable

Fab Lab: Creating Design-to-Prototype Learning Modules at the Museum of Science and Industry (sequence unknown), IPRO 333 - Deliverables: IPRO 333 Brochure F09

The primary objective of IPRO 333 is to partner the knowledge and ideas of young engineers, architects, and scientists at IIT with the resources of the Museum of Science and Industry (MSI) in Chicago. This partnership endeavors to help the museum's Fabrication Laboratory (Fab Lab) maximize its potential as a resource for museum guests, young and old, as well as for IIT students, staff, and faculty.Sponsorship: Museum of Science and Industry. Steven Willis- Director, Fabrication LabDeliverables for IPRO 333: Fab Lab: Creating Design-to-Prototype Learning Modules at the Museum of Science and Industry for the fall 2009 semeste

Fab Lab: Creating Design-to-Prototype Learning Modules at the Museum of Science and Industry (sequence unknown), IPRO 333 - Deliverables: IPRO 333 Final Report F09

The primary objective of IPRO 333 is to partner the knowledge and ideas of young engineers, architects, and scientists at IIT with the resources of the Museum of Science and Industry (MSI) in Chicago. This partnership endeavors to help the museum's Fabrication Laboratory (Fab Lab) maximize its potential as a resource for museum guests, young and old, as well as for IIT students, staff, and faculty.Sponsorship: Museum of Science and Industry. Steven Willis- Director, Fabrication LabDeliverables for IPRO 333: Fab Lab: Creating Design-to-Prototype Learning Modules at the Museum of Science and Industry for the fall 2009 semeste

Fab Lab (Semester Unknown) IPRO 333: FabLabIPRO333BrochureF09

Fabrication Laboratories, or Fab Labs, were started as a community outreach program by the Massachusetts Institute of Technology and provide digital fabrication tools for rapid prototyping to the general public. The Museum of Science and Industry has partnered with this IPRO to further develop the Fab Lab at their site. IPRO 333 currently works with the administration in the Fab lab of MSI to design materials and activities for increasing the use of the laboratory. IPRO 333 aims to broaden the possible uses of the lab, promote membership at the museum, and increasing participation by the community in science and technology programs at the museum.Sponsorship: Fabrication Laboratories, or Fab LabsDeliverable

Fab Lab (Semester Unknown) IPRO 333: FabLabIPRO333MidTermPresentationF09

Fabrication Laboratories, or Fab Labs, were started as a community outreach program by the Massachusetts Institute of Technology and provide digital fabrication tools for rapid prototyping to the general public. The Museum of Science and Industry has partnered with this IPRO to further develop the Fab Lab at their site. IPRO 333 currently works with the administration in the Fab lab of MSI to design materials and activities for increasing the use of the laboratory. IPRO 333 aims to broaden the possible uses of the lab, promote membership at the museum, and increasing participation by the community in science and technology programs at the museum.Sponsorship: Fabrication Laboratories, or Fab LabsDeliverable