ORION Low Cost Laser Analysis

We show that laser-target interaction physics demands the shortest laser pulse of which hardware is capable (but not less than 100 ps) in the ORION ground-based laser concept. We compare two leading ways to achieve such pulses - SRS/SBS cascade compression and grating compression - with the standard MOPA approach, and conclude that the first of these is most robust. However, the state of the art in laser devices will require a year or two to implement these ideas. We present a pulse format and beam footprint protocol which will solve the conflict between relativistic lookahead and beam tilt and should permit all-laser active acquisition and tracking in ORION

Removing Orbital Debris with Lasers

Orbital debris in low Earth orbit (LEO) are now sufficiently dense that the use of LEO space is threatened by runaway collisional cascading. A problem predicted more than thirty years ago, the threat from debris larger than about 1 cm demands serious attention. A promising proposed solution uses a high power pulsed laser system on the Earth to make plasma jets on the objects, slowing them slightly, and causing them to re-enter and burn up in the atmosphere. In this paper, we reassess this approach in light of recent advances in low-cost, light-weight modular design for large mirrors, calculations of laser-induced orbit changes and in design of repetitive, multi-kilojoule lasers, that build on inertial fusion research. These advances now suggest that laser orbital debris removal (LODR) is the most cost-effective way to mitigate the debris problem. No other solutions have been proposed that address the whole problem of large and small debris. A LODR system will have multiple uses beyond debris removal. International cooperation will be essential for building and operating such a system.Comment: 37 pages, 15 figures, in preparation for submission to Advances in Space Researc

Energy coupling in short pulse laser solid interactions and its impact for space debris removal

Significant advances have been made over the last decade to improve the performance, efficiency, and contrast of high peak and average power laser systems, driven by their use in a wide variety of fields, from the industrial to the scientific. As the contrast of the lasers has improved, interactions with contrasts of 1012 are now routinely undertaken. At such high contrasts, there is negligible preplasma formation and the ionized surface layer created by subpicosecond-duration pulses typically forms a highly reflective "plasma mirror" capable of reflecting between 70% and 90% of the incident energy. Although such interactions are of significant interest for applications such as harmonic source production and to enable the underlying physics to be studied, their low absorption can limit their usefulness for applications such as space debris removal

Laser impulse coupling measurements at 400 fs and 80 ps using the LULI facility at 1057 nm wavelength

At the École Polytechnique « LULI » facility, we have measured the impulse coupling coefficient Cm (target momentum per joule of incident laser light) with several target materials in vacuum, at 1057 nm and 400 fs and 80 ps pulse duration. A total of 64 laser shots were completed in a two-week experimental campaign, divided between the two pulse durations and among the materials. Our main purpose was to resolve wide discrepancies among reported values for Cm in the 100 ps region, where many applications exist. A secondary purpose was to compare Cm at 400 fs and 80 ps pulse duration. The 80 ps pulse was obtained by partial compression. Materials were Al, Ta, W, Au, and POM (polyoxymethylene, trade name Delrin). One application of these results is to pulsed laser ablation propulsion in space, including space debris re-entry, where narrow ranges in Cm and specific impulse Isp spell the difference between dramatic and uneconomical performance. We had difficulty measuring mass loss from single shots. Imparted momentum in single laser shots was determined using pendulum deflection and photonic Doppler velocimetry. Cm was smaller at the 400 fs pulse duration than at 80 ps. To our surprise, Cm for Al at 80 ps was at most 30 N/MW with 30 kJ/m2 incident fluence. On the other extreme, polyoxymethylene (POM, trade name Delrin) demonstrated 770 N/MW under these conditions. Together, these results offer the possibility of designing a Cm value suited to an application, by mixing the materials appropriately

Transfers from Earth to LEO and LEO to interplanetary space using lasers

New data on some materials at 80ps pulse duration and 1057 nm wavelength give us the option of proportionally combining them to obtain arbitrary values between 35 (aluminum) and 800 N/MW (POM, polyoxymethylene) for momentum coupling coefficient Cm. Laser ablation physics lets us transfer to LEO from Earth, or to interplanetary space using repetitively pulsed lasers and Cm values appropriate for each mission. We discuss practical results for lifting small payloads from Earth to LEO, and space missions such as a cis-Mars orbit with associated laser system parameters

Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds

Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses

BACKGROUND & AIMS: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. METHODS: Serum levels of IGF1 and other proteins were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 level associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10-4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10-5). Colorectal cancer risk was associated with only 1 variant in IGFBP3 (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. CONCLUSIONS: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice