The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

Mineralogy of Great Salt Lake: An Analogue for Martian Evaporites

Gypsum (CaSO4 · 2H2O) and mirabilite (Na2SO4 · 10H2O) are common precipitates at the Great Salt Lake (GSL). NASA’s Mars Exploration Rover, Opportunity, found veins of gypsum deposited by water in 2011 and gypsum has been detected on Mars as early as 2005 by the ESA’s Mars Express Orbiter. On Earth, gypsum is formed in hypersaline environments, in minerals left behind when water evaporates, trapping microorganisms in fluid inclusions. Likewise, GSL mirabilite develops when mineral-rich groundwater meets cold winter air to create crystalline structures. While there is no physical evidence of mirabilite on Mars, HiRISE Image data show white mounds that some experts hypothesize are related to saline ground waters. Gypsum obtained from Great Salt Lake was used to develop a method to extract halophilic archaea and culture it in the lab. The method obtained could be used to isolate potential microorganisms present in gypsum samples from Mars. Mirabilite is currently under investigation for its ability to enrich halophilic life

Making Deep Heatmaps Robust to Partial Occlusions for 3D Object Pose Estimation

We introduce a novel method for robust and accurate 3D object pose estimation from a single color image under large occlusions. Following recent approaches, we first predict the 2D projections of 3D points related to the target object and then compute the 3D pose from these correspondences using a geometric method. Unfortunately, as the results of our experiments show, predicting these 2D projections using a regular CNN or a Convolutional Pose Machine is highly sensitive to partial occlusions, even when these methods are trained with partially occluded examples. Our solution is to predict heatmaps from multiple small patches independently and to accumulate the results to obtain accurate and robust predictions. Training subsequently becomes challenging because patches with similar appearances but different positions on the object correspond to different heatmaps. However, we provide a simple yet effective solution to deal with such ambiguities. We show that our approach outperforms existing methods on two challenging datasets: The Occluded LineMOD dataset and the YCB-Video dataset, both exhibiting cluttered scenes with highly occluded objects. Project website: https://www.tugraz.at/institute/icg/research/team-lepetit/research-projects/robust-object-pose-estimation

Multispectral Imagery And Higher Level Products Available From The Land Processes Distributed Active Archive Center, U.S. Geological Survey EROS Data Center

There are many types of multispectral imagery and higher level products available from the Land Processes Distributed Active Archive Center at the U.S. Geological Survey EROS Data Center, including data produced from the Moderate Resolution Imaging Spectroradiometer on the Terra and Aqua satellites, the Enhanced Thematic Mapper Plus on Landsat 7, and the Advanced Spaceborne Thermal Emission and Reflection Radiometer on Terra. Information on these various instruments and their respective data products is available on the World Wide Web. The data products can be obtained by using the NASA EOS Data Gateway

Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes

High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents. We found that mice whose rhMBL serum concentrations were increased ≥7-fold above average human levels survived otherwise fatal Ebola virus infections and became immune to virus rechallenge. Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach

Geographic variation of mutagenic exposures in kidney cancer genomes

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics

Automated assessment of COVID-19 reporting and data system and chest CT severity scores in patients suspected of having COVID-19 using artificial intelligence

Background: The coronavirus disease 2019 (COVID-19) pandemic has spread across the globe with alarming speed, morbidity, and mortality. Immediate triage of patients with chest infections suspected to be caused by COVID-19 using chest CT may be of assistance when results from definitive viral testing are delayed.Purpose: To develop and validate an artificial intelligence (AI) system to score the likelihood and extent of pulmonary COVID-19 on chest CT scans using the COVID-19 Reporting and Data System (CO-RADS) and CT severity scoring systems.Materials and Methods: The CO-RADS AI system consists of three deep-learning algorithms that automatically segment the five pulmonary lobes, assign a CO-RADS score for the suspicion of COVID-19, and assign a CT severity score for the degree of parenchymal involvement per lobe. This study retrospectively included patients who underwent a nonenhanced chest CT examination because of clinical suspicion of COVID-19 at two medical centers. The system was trained, validated, and tested with data from one of the centers. Data from the second center served as an external test set. Diagnostic performance and agreement with scores assigned by eight independent observers were measured using receiver operating characteristic analysis, linearly weighted kappa values, and classification accuracy.Results: A total of 105 patients (mean age, 62 years +/- 16 [standard deviation]; 61 men) and 262 patients (mean age, 64 years +/- 16; 154 men) were evaluated in the internal and external test sets, respectively. The system discriminated between patients with COVID-19 and those without COVID-19, with areas under the receiver operating characteristic curve of 0.95 (95% CI: 0.91, 0.98) and 0.88 (95% CI: 0.84, 0.93), for the internal and external test sets, respectively. Agreement with the eight human observers was moderate to substantial, with mean linearly weighted k values of 0.60 +/- 0.01 for CO-RADS scores and 0.54 +/- 0.01 for CT severity scores.Conclusion: With high diagnostic performance, the CO-RADS AI system correctly identified patients with COVID-19 using chest CT scans and assigned standardized CO-RADS and CT severity scores that demonstrated good agreement with findings from eight independent observers and generalized well to external data. (C) RSNA, 2020Cardiovascular Aspects of Radiolog