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The mosaicking of global planetary data sets allows for the examination of local, regional, and global scale processes on all planetary bodies. Processing techniques that allow us and other users to crate mosaics of tens of thousands of images are documented along with the associated errors introduced by each image‐processing algorithm. These techniques (e.g., non‐uniformity correction, running contrast stretches, line and row correlated noise removal, and random noise removal) were originally developed for the 2001 Mars Odyssey Thermal Emission Imaging System (THEMIS) infrared multispectral imager data but can be adapted and applied to other data sets by the alteration of input parameters. The techniques for mosaicking planetary image data sets (e.g., image registration, blending, and normalization) are also presented along with the generation of qualitative and quantitative products. These techniques are then applied to generate THEMIS daytime and nighttime infrared, Viking, Context Imager (CTX), and Mars Orbiter Camera (MOC) visible mosaics using a variety of input and output types at a variety of scales. By creating mosaics of the same area using different data sets such as those that illustrate compositional diversity, thermophysical properties, or small‐scale morphology, it is possible to view the surface of the planet and geologic problems through many different perspectives. In addition to the techniques used to create large‐scale seamless mosaics, we also present the THEMIS daytime and nighttime relative temperature global mosaics, which are the highest resolution (100m/pixel) global scale data sets available for Mars to date.

The median survival for glioblastoma patients is ~15 months despite aggressive surgery and radio-chemotherapy approaches. Thus, developing new therapeutics is necessary to improve the treatment of these invasive brain tumors, which are known to show high levels of the eukaryotic initiation factor, eIF4E, a potent oncogene. Ribavirin, the only clinically approved drug known to target eIF4E, is an anti-viral molecule currently used in hepatitis C treatment. Here, we report the effect of ribavirin on proliferation, cell cycle, cell death and migration of several human and murine glioma cell lines, as well as human glioblastoma stem-like cells, in vitro. In addition, we tested ribavirin efficacy in vivo, alone and in combination with temozolomide and radiation. Our work showed that ribavirin inhibits glioma cell growth and migration, and increases cell cycle arrest and cell death, potentially through modulation of the eIF4E, EZH2 and ERK pathways. We also demonstrate that ribavirin treatment in combination with temozolomide or irradiation increases cell death in glioma cells. Finally and most importantly, ribavirin treatment in vivo significantly enhances chemo-radiotherapy efficacy and improves survival of rats and mice orthotopically implanted with gliosarcoma tumors or glioma stem-like cells, respectively. On the basis of these results, we propose that ribavirin represents a new therapeutic option for glioblastoma patients as an enhancer of the cytotoxic effects of temozolomide and radiotherapy.

AKT- a key molecular regulator of PI-3K signaling pathway, is somatically mutated in diverse solid cancer types, and aberrant AKT activation promotes altered cancer cell growth, survival, and metabolism 1 – 8 . The most common of AKT mutations (AKT1 E17K) sensitizes affected solid tumors to AKT inhibitor therapy 7 , 8 . However, the pathway dependence and inhibitor sensitivity of the long tail of potentially activating mutations in AKT is poorly understood, limiting our ability to act clinically in prospectively characterized cancer patients. Here we show, through population-scale driver mutation discovery combined with functional, biological, and therapeutic studies that some but not all missense mutations activate downstream AKT effector pathways in a growth factor-independent manner and sensitize tumor cells to diverse AKT inhibitors. A distinct class of small in-frame duplications paralogous across AKT isoforms induce structural changes different than those of activating missense mutations, leading to a greater degree of membrane affinity, AKT activation, and cell proliferation as well as pathway dependence and hyper-sensitivity to ATP-competitive, but not allosteric AKT inhibitors. Assessing these mutations clinically, we conducted a phase II clinical trial testing the AKT inhibitor capivasertib (AZD5363) in patients with solid tumors harboring AKT alterations (NCT03310541). Twelve patients were enrolled, out of which six harbored AKT1-3 non-E17K mutations. The median progression free survival (PFS) of capivasertib therapy was 84 days (95% CI 50-not reached) with an objective response rate of 25% ( n  = 3 of 12) and clinical benefit rate of 42% ( n  = 5 of 12). Collectively, our data indicate that the degree and mechanism of activation of oncogenic AKT mutants vary, thereby dictating allele-specific pharmacological sensitivities to AKT inhibition. How different oncogenic Akt mutants can affect the response to Akt inhibitors is currently unclear. Here, the authors analyse somatic mutations of Akt1-3 isoforms in several human cancers, investigate their oncogenic effects and therapeutic relevance in vitro and confirm some of their data in a clinical trial testing the AKT inhibitor capivasertib in patients with solid tumors harboring AKT alterations.

Cancers develop as a result of driver mutations 1 , 2 that lead to clonal outgrowth and the evolution of disease 3 , 4 . The discovery and functional characterization of individual driver mutations are central aims of cancer research, and have elucidated myriad phenotypes 5 and therapeutic vulnerabilities 6 . However, the serial genetic evolution of mutant cancer genes 7 , 8 and the allelic context in which they arise is poorly understood in both common and rare cancer genes and tumour types. Here we find that nearly one in four human tumours contains a composite mutation of a cancer-associated gene, defined as two or more nonsynonymous somatic mutations in the same gene and tumour. Composite mutations are enriched in specific genes, have an elevated rate of use of less-common hotspot mutations acquired in a chronology driven in part by oncogenic fitness, and arise in an allelic configuration that reflects context-specific selective pressures. cis -acting composite mutations are hypermorphic in some genes in which dosage effects predominate (such as TERT ), whereas they lead to selection of function in other genes (such as TP53 ). Collectively, composite mutations are driver alterations that arise from context- and allele-specific selective pressures that are dependent in part on gene and mutation function, and which lead to complex—often neomorphic—functions of biological and therapeutic importance. Composite mutations, of two or more nonsynonymous somatic mutations in the same cancer-associated gene, are present in nearly one in four human tumours.

Throughout life, cells accrue mutations. It now emerges that longer-lived animals acquire mutations at a slower rate than do short-lived species, potentially explaining why cancer risk does not increase with lifespan. Long-lived species have a slower mutation rate than short-lived species.

Reliably monitoring global urbanization is of key importance for supporting a variety of applications involving the analysis of human presence (e.g., socioeconomic development, population distribution, risks assessment, epidemiology, conservation areas protection, etc.). To this purpose, in order to accurately outline the actual settlement extent globally we generated the World Settlement Footprint (WSF) 2015, i.e. a 10m resolution binary mask derived by jointly exploiting multitemporal optical and radar satellite imagery, which outperforms all other existing similar layers. Furthermore, to characterize the urbanization occurred in the last three decades, we recently completed the WSF Evolution, i.e. a novel dataset outlining the growth of settlement extent globally at 30m spatial resolution on a yearly basis from 1985 to 2015.

Compositional mapping of Mars at the 100-metre scale with the Mars Odyssey Thermal Emission Imaging System (THEMIS) has revealed a wide diversity of igneous materials. Volcanic evolution produced compositions from low-silica basalts to high-silica dacite in the Syrtis Major caldera. The existence of dacite demonstrates that highly evolved lavas have been produced, at least locally, by magma evolution through fractional crystallization. Olivine basalts are observed on crater floors and in layers exposed in canyon walls up to 4.5 km beneath the surface. This vertical distribution suggests that olivine-rich lavas were emplaced at various times throughout the formation of the upper crust, with their growing inventory suggesting that such ultramafic (picritic) basalts may be relatively common. Quartz-bearing granitoid rocks have also been discovered, demonstrating that extreme differentiation has occurred. These observations show that the martian crust, while dominated by basalt, contains a diversity of igneous materials whose range in composition from picritic basalts to granitoids rivals that found on the Earth. Martian minerals mapped Infrared measurements from the orbiting Mars Odyssey probe have been used to produce the most detailed map yet of mineral distribution on the martian surface. The rocks show a surprisingly complex volcanic history. Lavas range from primitive mantle-derived basalts to silica-rich rocks that probably formed in magma chambers following the re-melting of previously erupted rocks. Also present are volcanic basalts that contain more than 20% olivine, a mineral that is quickly weathered by water. Similar olivine-rich rocks were found in eroded canyon walls and ancient crater floors that date back billions of years. This suggests that during each period of olivine layer deposition, Mars did not have extensive water on its surface.

The extent of cell-to-cell variation in tumor mitochondrial DNA (mtDNA) copy number and genotype, and the phenotypic and evolutionary consequences of such variation, are poorly characterized. Here we use amplification-free single-cell whole-genome sequencing (Direct Library Prep (DLP+)) to simultaneously assay mtDNA copy number and nuclear DNA (nuDNA) in 72,275 single cells derived from immortalized cell lines, patient-derived xenografts and primary human tumors. Cells typically contained thousands of mtDNA copies, but variation in mtDNA copy number was extensive and strongly associated with cell size. Pervasive whole-genome doubling events in nuDNA associated with stoichiometrically balanced adaptations in mtDNA copy number, implying that mtDNA-to-nuDNA ratio, rather than mtDNA copy number itself, mediated downstream phenotypes. Finally, multimodal analysis of DLP+ and single-cell RNA sequencing identified both somatic loss-of-function and germline noncoding variants in mtDNA linked to heteroplasmy-dependent changes in mtDNA copy number and mitochondrial transcription, revealing phenotypic adaptations to disrupted nuclear/mitochondrial balance. Amplification-free single-cell whole-genome sequencing shows that genomic, evolutionary and biophysical factors collectively drive cell-to-cell variation in mitochondrial DNA copy number.

Mitochondrial DNA (mtDNA) encodes protein subunits and translational machinery required for oxidative phosphorylation (OXPHOS). Using repurposed whole-exome sequencing data, in the present study we demonstrate that pathogenic mtDNA mutations arise in tumours at a rate comparable to those in the most common cancer driver genes. We identify OXPHOS complexes as critical determinants shaping somatic mtDNA mutation patterns across tumour lineages. Loss-of-function mutations accumulate at an elevated rate specifically in complex I and often arise at specific homopolymeric hotspots. In contrast, complex V is depleted of all non-synonymous mutations, suggesting that impairment of ATP synthesis and mitochondrial membrane potential dissipation are under negative selection. Common truncating mutations and rarer missense alleles are both associated with a pan-lineage transcriptional programme, even in cancer types where mtDNA mutations are comparatively rare. Pathogenic mutations of mtDNA are associated with substantial increases in overall survival of colorectal cancer patients, demonstrating a clear functional relationship between genotype and phenotype. The mitochondrial genome is therefore frequently and functionally disrupted across many cancers, with major implications for patient stratification, prognosis and therapeutic development. Using whole-exome sequencing data, Gorelick et al. identify lineage-specific somatic mutations in mitochondrial DNA that affect cancer progression and patient prognosis.

The Miniature Thermal Emission Spectrometer (Mini-TES) on Spirit has studied the mineralogy and thermophysical properties at Gusev crater. Undisturbed soil spectra show evidence for minor carbonates and bound water. Rocks are olivinerich basalts with varying degrees of dust and other coatings. Dark-toned soils observed on disturbed surfaces may be derived from rocks and have derived mineralogy (±5 to 10%) of 45% pyroxene (20% Ca-rich pyroxene and 25% pigeonite), 40% sodic to intermediate plagioclase, and 15% olivine (forsterite 45% ±5 to 10). Two spectrally distinct coatings are observed on rocks, a possible indicator of the interaction of water, rock, and airfall dust. Diurnal temperature data indicate particle sizes from 40 to 80 µm in hollows to ~0.5 to 3 mm in soils.