Extension of Cloud Computing to Small Satellites

Time-to-insight is a critical measure in a number of satellite mission applications: detection and warning of fast-moving events like fires and floods, or identification and tracking of satellites or missiles, for example. Current data flows delay the time-to-insight on the order of minutes or hours, as all collected data must be downlinked in one or more contact windows, then transited over terrestrial networks to the location of the analytic software. Additionally, mission applications on spacecraft are often static: built prior to launch, they cannot rapidly adapt to changing needs based on these insights. To reduce time-to-insight and provide a dynamic application update capability, Amazon Web Services (AWS), D-Orbit, and Unibap conducted a joint experiment in which we deployed AWS edge compute and network management software onto Unibap’s SpaceCloud® iX5 platform for edge computing in space, integrated onto a D-Orbit ION Satellite Carrier launched into low-earth orbit (LEO) in early 2022. In this paper, we present the results of this experiment. We will discuss the software specifics and network management capabilities we developed to write mission applications and update those mission applications on-orbit, and detail the process of mission deployment and modification, communications latency, and data volume reduction. We will also discuss how the space and satellite community can use this capability to deploy new applications, performing complex tasks and reducing time-to-insight, to cloud-enabled satellites immediately without needing to wait for a new launch

Concept 3

Concept III, the publication of Syracuse University School of Architecture of 1964, is devoted to the subject which occupies most of the time and hopefully much of the thought of its students: architectural education

High-spatial-resolution imaging of thermal emission from debris disks

We have obtained sub-arcsec mid-IR images of a sample of debris disks within 100 pc. For our sample of nineteen A-type debris disk candidates chosen for their IR excess, we have resolved, for the first time, five sources plus the previously resolved disk around HD 141569. Two other sources in our sample have been ruled out as debris disks since the time of sample selection. Three of the six resolved sources have inferred radii of 1-4 AU (HD 38678, HD 71155, and HD 181869), and one source has an inferred radius ~10-30 AU (HD 141569). Among the resolved sources with detections of excess IR emission, HD 71155 appears to be comparable in size (r~2 AU) to the solar system's asteroid belt, thus joining Zeta Lep (HD 38678, reported previously) to comprise the only two resolved sources of that class. Two additional sources (HD 95418 and HD 139006) show spatial extent that implies disk radii of ~1-3 AU, although the excess IR fluxes are not formally detected with better than 2-sigma significance. For the unresolved sources, the upper limits on the maximum radii of mid-IR disk emission are in the range ~1-20 AU, four of which are comparable in radius to the asteroid belt. We have compared the global color temperatures of the dust to that expected for the dust in radiative equilibrium at the distances corresponding to the observed sizes or limits on the sizes. In most cases, the temperatures estimated via these two methods are comparable, and therefore, we see a generally consistent picture of the inferred morphology and the global mid-IR emission. Finally, while our sample size is not statistically significant, we notice that the older sources (>200 Myr) host much warmer dust (T > 400 K) than younger sources (in the 10s of Myr).Comment: 46 pages, 12 figure

Potential Risk Factors for Cutaneous Squamous Cell Carcinoma include Oral Contraceptives: Results of a Nested Case-Control Study

Recently, a population-based case-control study observed a 60% increased odds ratio (OR) for cutaneous squamous cell carcinoma (SCC) among women who had ever used oral contraceptives (OCs) compared with non users (95% confidence interval (CI) = 1.0–2.5). To further characterize the putative association between OC use and SCC risk, we conducted a nested case-control study using a large retrospective cohort of 111,521 Kaiser Permanente Northern California members. Multivariable conditional logistic regression was used to estimate ORs and CIs adjusting for known and hypothesized SCC risk factors. Pre-diagnostic OC use was associated with a statistically significant increased OR for SCC in univariate analysis (OR = 2.4, CI = 1.2–4.8), with borderline statistical significance in multivariable analysis (CI = 2.0, CI = 0.91–4.5). Given the high incidence of SCC in the general population and the prevalent use of OCs among women in the United States, there is a need for more large, carefully designed epidemiologic studies to determine whether the observed association between OC use and SCC can be replicated and to better understand the etiologic basis of an association if one exists

Recent Region-wide Declines in Caribbean Reef Fish Abundance

Profound ecological changes are occurring on coral reefs throughout the tropics, with marked coral cover losses and concomitant algal increases, particularly in the Caribbean region. Historical declines in the abundance of large Caribbean reef fishes likely reflect centuries of overexploitation. However, effects of drastic recent degradation of reef habitats on reef fish assemblages have yet to be established. By using meta-analysis, we analyzed time series of reef fish density obtained from 48 studies that include 318 reefs across the Caribbean and span the time period 1955–2007. Our analyses show that overall reef fish density has been declining significantly for more than a decade, at rates that are consistent across all subregions of the Caribbean basin (2.7% to 6.0% loss per year) and in three of six trophic groups. Changes in fish density over the past half-century are modest relative to concurrent changes in benthic cover on Caribbean reefs. However, the recent significant decline in overall fish abundance and its consistency across several trophic groups and among both fished and nonfished species indicate that Caribbean fishes have begun to respond negatively to habitat degradation

Visualization of Src activity at different compartments of the plasma membrane by FRET imaging

SummaryMembrane compartments function as segregated signaling platforms for different cellular functions. It is not clear how Src is regulated at different membrane compartments. To visualize local Src activity in live cells, a FRET-based Src biosensor was targeted in or outside of lipid rafts at the plasma membrane, via acylation or prenylation modifications on targeting tags either directly fused to the biosensor or coupled to the biosensor through an inducible heterodimerization system. In response to growth factors and pervanadate, the induction of Src activity in rafts was slower and weaker, dependent on actin and possibly its mediated transportation of Src from perinuclear regions to the plasma membrane. In contrast, the induction of Src activity in nonrafts was faster and stronger, dependent on microtubules. Hence, Src activity is differentially regulated via cytoskeleton at different membrane compartments

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

Phase 1 dose-expansion study of oral TP-1287, a cyclin-dependent kinase 9 (CDK9) inhibitor, in patients with Ewing sarcoma (EWS)

TPS11589 Background: Cyclin-dependent kinase 9 (CDK9) blockade inhibits tumor growth and progression by impairing the transcription of key oncogenes, such as myeloid cell leukemia-1 (MCL-1) and c-MYC. CDK9 overexpression has been observed in sarcoma patients (pts), and CDK9 has emerged as a potential therapeutic target in pts with sarcoma. TP-1287 is an investigational orally delivered phosphate prodrug of the CDK9 inhibitor alvocidib. In preclinical studies, TP-1287 has been shown to decrease MCL-1 expression and phosphorylation of RNA polymerase II (RPB1), and inhibit tumor growth in an Ewing sarcoma (EWS) mouse model. Phase 1 dose-escalation in solid tumors has completed and TP-1287 is being investigated in a dose expansion cohort in pts with EWS (NCT03604783). The design of the expansion part of the trial in pts with EWS is herein described. Methods: Up to thirty pts with EWS will be enrolled in this dose expansion cohort. Key eligibility criteria are age ≥18 years (≥12 years, if weight ≥40 kg); histologically confirmed locally advanced or metastatic unresectable EWS; received 1 to 5 prior lines of treatment including an anthracycline; one or more measurable tumors per the RECIST v1.1; ECOG performance status of ≤1; acceptable liver and renal function, and acceptable hematologic and coagulation status; no treatment with surgery, chemotherapy, or investigational therapy within 28 days or 5 half-lives. Eligible pts will be treated with oral TP-1287 monotherapy RP2D established from the dose escalation part (11 mg BID, continuous dosing in a 28-day treatment cycle) and will continue treatment until treatment-related adverse event or disease progression. Assessments will be performed on Day 1 and Day 15 of each cycle. Tumor response assessment will be done after Cycle 2 and at the end of every other cycle thereafter. The primary objectives are objective response rate (ORR) and clinical benefit rate (CBR) ; secondary objectives are median progression-free survival (PFS), PFS rate at 16-weeks and 24-weeks and safety; and exploratory objectives include evaluation of systemic exposure and pharmacodynamics. Safety data will be reviewed on an ongoing basis and a Bayesian approach will be used to assess the efficacy data. Statistical analysis for safety and efficacy parameters will be primarily descriptive in nature. EWS dose expansion cohort is currently recruiting in the United States. Clinical trial information: NCT03604783