Advances in Deep Space Exploration via Simulators & Deep Learning

The NASA Starlight and Breakthrough Starshot programs conceptualize fast interstellar travel via small relativistic spacecraft that are propelled by directed energy. This process is radically different from traditional space travel and trades large and slow spacecraft for small, fast, inexpensive, and fragile ones. The main goal of these wafer satellites is to gather useful images during their deep space journey. We introduce and solve some of the main problems that accompany this concept. First, we need an object detection system that can detect planets that we have never seen before, some containing features that we may not even know exist in the universe. Second, once we have images of exoplanets, we need a way to take these images and rank them by importance. Equipment fails and data rates are slow, thus we need a method to ensure that the most important images to humankind are the ones that are prioritized for data transfer. Finally, the energy on board is minimal and must be conserved and used sparingly. No exoplanet images should be missed, but using energy erroneously would be detrimental. We introduce simulator-based methods that leverage artificial intelligence, mostly in the form of computer vision, in order to solve all three of these issues. Our results confirm that simulators provide an extremely rich training environment that surpasses that of real images, and can be used to train models on features that have yet to be observed by humans. We also show that the immersive and adaptable environment provided by the simulator, combined with deep learning, lets us navigate and save energy in an otherwise implausible way

NanoBiT ‐ and NanoBiT/BRET ‐based assays allow the analysis of binding kinetics of Wnt‐3a to endogenous Frizzled 7 in a colorectal cancer model

Background and Purpose Wnt binding to Frizzleds (FZD) is a crucial step that leads to the initiation of signalling cascades governing multiple processes during embryonic development, stem cell regulation and adult tissue homeostasis. Recent efforts have enabled us to shed light on Wnt–FZD pharmacology using overexpressed HEK293 cells. However, assessing ligand binding at endogenous receptor expression levels is important due to differential binding behaviour in a native environment. Here, we study FZD paralogue, FZD$_{7}$, and analyse its interactions with Wnt-3a in live CRISPR-Cas9-edited SW480 cells typifying colorectal cancer. Experimental Approach SW480 cells were CRISPR-Cas9-edited to insert a HiBiT tag on the N-terminus of FZD$_{7}$, preserving the native signal peptide. These cells were used to study eGFP-Wnt-3a association with endogenous and overexpressed HiBiT-FZD$_{7}$ using NanoBiT/bioluminescence resonance energy transfer (BRET) and NanoBiT to measure ligand binding and receptor internalization. Key Results With this new assay the binding of eGFP-Wnt-3a to endogenous HiBiT-FZD$_{7}$ was compared with overexpressed receptors. Receptor overexpression results in increased membrane dynamics, leading to an apparent decrease in binding on-rate and consequently in higher, up to 10 times, calculated Kd. Thus, measurements of binding affinities to FZD$_{7}$ obtained in overexpressed cells are suboptimal compared with the measurements from endogenously expressing cells. Conclusions and Implications Binding affinity measurements in the overexpressing cells fail to replicate ligand binding affinities assessed in a (patho)physiologically relevant context where receptor expression is lower. Therefore, future studies on Wnt–FZD$_{7}$ binding should be performed using receptors expressed under endogenous promotion

Associations Between C-Reactive Protein, Insulin Sensitivity, and Resting Metabolic Rate in Adults: A Mediator Analysis

Objective: Long-term positive energy balance promotes the development of obesity, a main risk factor for type 2 diabetes mellitus (T2DM). While an association between increased resting metabolic rate (RMR) and insulin sensitivity (IS) was shown previously, the underlying mechanisms remain unclear. Aim of the mediator analysis was to investigate the role of inflammation within the association between RMR and IS.Methods: Anthropometric, clinical, and lifestyle data were collected according to standard operating procedures. RMR was measured using indirect calorimetry. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as an IS parameter and C-reactive protein (CRP) was measured to represent the inflammatory status. Statistical analyses were performed using SPSS.Results: The analysis included 782 adults (517 females) with a mean age of 32.4 ± 12.0 years and a mean body mass index (BMI) of 24.6 ± 5.2 kg/m2. Regression analysis indicated a significant evidence for associations between RMR and HOMA-IR (ß = 39.3 ± 7.3 kcal/d; p ≤ 0.001) and CRP and HOMA-IR (ß = 0.5 ± 0.1; p ≤ 0.001) after adjustment for fat-free mass, sex, age, and study site. Results of the mediator analysis did not support the hypothesis that CRP is a mediator for the association between RMR and HOMA-IR. These results did not change after participant stratification according to sex or BMI.Conclusion: A significant evidence for an association between RMR and IS was shown in a large cohort. However, the inflammatory status, determined via CRP levels, was not a mediator within this association

Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS

Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS

APOSTEL 2.0 Recommendations for Reporting Quantitative Optical Coherence Tomography Studies.

OBJECTIVE To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations. METHODS To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms "quantitative" and "optical coherence tomography" from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes. RESULTS A total of 116 authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans, and suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants' consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%. CONCLUSIONS The modified Delphi method resulted in an expert-led guideline (evidence Class III; Grading of Recommendations, Assessment, Development and Evaluations [GRADE] criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition analysis, nomenclature and abbreviations, and statistical approach. It will be essential to update these recommendations to new research and practices regularly

Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation

Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet-neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet-neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation