Background Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are ...limited data regarding the prognostic significance of these mutations in a real-world setting. Methods This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). Results Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR 95% CI, 1.4 0.9–2.3; p = 0.1; second-line subset of first-line cohort, HR, 1.6 1.3–2.0; p = 0.0002) or chemotherapy (first-line, HR, 1.4 1.2–1.6; p < 0.0001); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. Conclusions This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Clay minerals, recently discovered to be widespread in Mars's Noachian terrains, indicate long-duration interaction between water and rock over 3.7 billion years ago. Analysis of how they formed ...should indicate what environmental conditions prevailed on early Mars. If clays formed near the surface by weathering, as is common on Earth, their presence would indicate past surface conditions warmer and wetter than at present. However, available data instead indicate substantial Martian clay formation by hydrothermal groundwater circulation and a Noachian rock record dominated by evidence of subsurface waters. Cold, arid conditions with only transient surface water may have characterized Mars's surface for over 4 billion years, since the early-Noachian period, and the longest-duration aqueous, potentially habitable environments may have been in the subsurface.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Modified clay minerals on Mars
Sedimentary rocks exposed in Gale crater on Mars contain extensive clay minerals. Bristow
et al.
analyzed drill samples collected by the Curiosity rover as it climbed ...up sedimentary layers in the crater. They found evidence of past reactions with liquid water and sulfate brines, which could have percolated through the clay from an overlying sulfate deposit. Similar sulfate deposits are widespread across the planet and represent some of the last sedimentary rocks to form before the planet lost its surface liquid water, so the results inform our understanding of the geologic processes that occurred as Mars dried out.
Science, abg5449, this issue p.
198
Clay minerals examined by the Curiosity rover contain evidence of reactions with sulfate brines as Mars dried out.
Mars’ sedimentary rock record preserves information on geological (and potential astrobiological) processes that occurred on the planet billions of years ago. The
Curiosity
rover is exploring the lower reaches of Mount Sharp, in Gale crater on Mars. A traverse from Vera Rubin ridge to Glen Torridon has allowed
Curiosity
to examine a lateral transect of rock strata laid down in a martian lake ~3.5 billion years ago. We report spatial differences in the mineralogy of time-equivalent sedimentary rocks <400 meters apart. These differences indicate localized infiltration of silica-poor brines, generated during deposition of overlying magnesium sulfate–bearing strata. We propose that destabilization of silicate minerals driven by silica-poor brines (rarely observed on Earth) was widespread on ancient Mars, because sulfate deposits are globally distributed.
Wind blowing over sand on Earth produces decimeter-wavelength ripples and hundred-meter— to kilometer-wavelength dunes: bedforms of two distinct size modes. Observations from the Mars Science ...Laboratory Curiosity rover and the Mars Reconnaissance Orbiter reveal that Mars hosts a third stable wind-driven bedform, with meter-scale wavelengths. These bedforms are spatially uniform in size and typically have asymmetric profiles with angle-of-repose lee slopes and sinuous crest lines, making them unlike terrestrial wind ripples. Rather, these structures resemble fluid-drag ripples, which on Earth include water-worked current ripples, but on Mars instead form by wind because of the higher kinematic viscosity of the low-density atmosphere. A reevaluation of the wind-deposited strata in the Burns formation (about 3.7 billion years old or younger) identifies potential wind-drag ripple stratification formed under a thin atmosphere.
We have developed a refined geologic map and stratigraphy for lower Mount Sharp using coordinated analyses of new spectral, thermophysical, and morphologic orbital data products. The Mount Sharp ...group consists of seven relatively planar units delineated by differences in texture, mineralogy, and thermophysical properties. These units are (1–3) three spatially adjacent units in the Murray formation which contain a variety of secondary phases and are distinguishable by thermal inertia and albedo differences, (4) a phyllosilicate‐bearing unit, (5) a hematite‐capped ridge unit, (6) a unit associated with material having a strongly sloped spectral signature at visible near‐infrared wavelengths, and (7) a layered sulfate unit. The Siccar Point group consists of the Stimson formation and two additional units that unconformably overlie the Mount Sharp group. All Siccar Point group units are distinguished by higher thermal inertia values and record a period of substantial deposition and exhumation that followed the deposition and exhumation of the Mount Sharp group. Several spatially extensive silica deposits associated with veins and fractures show that late‐stage silica enrichment within lower Mount Sharp was pervasive. At least two laterally extensive hematitic deposits are present at different stratigraphic intervals, and both are geometrically conformable with lower Mount Sharp strata. The occurrence of hematite at multiple stratigraphic horizons suggests redox interfaces were widespread in space and/or in time, and future measurements by the Mars Science Laboratory Curiosity rover will provide further insights into the depositional settings of these and other mineral phases.
Key Points
We have developed a stratigraphy for lower Mount Sharp using analyses of new spectral, thermophysical, and morphologic orbital data products
Siccar Point group records a period of deposition and exhumation that followed the deposition and exhumation of the Mount Sharp group
Late state silica enrichment and redox interfaces within lower Mount Sharp were pervasive and widespread in space and/or in time
Mars missions and Martian meteorites revealed how complex the Martian crust is. The occurrence of both alkaline and sub-alkaline igneous rocks of Noachian age (>3.7 Ga) in Gale crater indicates ...diverse magmatic processes, with sub-alkaline rocks likely formed through the partial melting of hydrous mafic rocks, as commonly observed on Earth. The orbital discovery of excavated evolved igneous rocks scattered in Noachian terrains raise questions about the petrology of the ancient Martian crust, long thought to be basaltic. A possibly evolved crust beneath a mafic cover is supported by geophysical and seismic measurements from the Insight lander that indicate the bulk crust has a lower density than expected if it were homogeneously basaltic. If localized magmatic processes could form evolved terrains, the detection of abundant intermediate to felsic Noachian crustal exposures through remote sensing suggest regional- to global-scale processes that produced evolved crustal component(s) that are now buried below mafic materials. Due to the lack of centimetric to millimetric textural imaging and compositional measurements, the petrology of such crust is ambiguous. Future orbiter, rover, and aerial missions should focus on Noachian exposed regions exhibiting evolved crustal characteristics to unfold the petrology of the Martian crust and its formation.
We present a parameterized convection model of Mars by incorporating a new heat-flow scaling law for stagnant-lid convection, to better understand how the evolution of Mars may be affected by mantle ...melting. Melting in the mantle during convection leads to the formation of a compositionally buoyant lithosphere, which may also be intrinsically more viscous by dehydration. The consequences of these melting effects on the evolution of terrestrial planets have not been explored before. The temporal evolution of crust and lithospheric mantle is modeled in a self-consistent manner considering mantle melting, convective instability, and the rewetting of dehydrated lithosphere from below by hydrogen diffusion. Though the effect of compositional buoyancy turns out to be minimal, the introduction of viscosity contrast between wet and dry mantle can considerably slow mantle cooling and sometimes lead to non-monotonic core cooling. Furthermore, with or without dehydration stiffening, our model predicts that the martian mantle must have been degassed more extensively (>80%) than previously suggested (<10%); the loss of such a large amount of water from the mantle to surface has significant implications about the role of water in the early surface and climate evolution of Mars.
A Field Guide to Finding Fossils on Mars McMahon, S.; Bosak, T.; Grotzinger, J. P. ...
Journal of geophysical research. Planets,
20/May , Letnik:
123, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The Martian surface is cold, dry, exposed to biologically harmful radiation and apparently barren today. Nevertheless, there is clear geological evidence for warmer, wetter intervals in the past that ...could have supported life at or near the surface. This evidence has motivated National Aeronautics and Space Administration and European Space Agency to prioritize the search for any remains or traces of organisms from early Mars in forthcoming missions. Informed by (1) stratigraphic, mineralogical and geochemical data collected by previous and current missions, (2) Earth's fossil record, and (3) experimental studies of organic decay and preservation, we here consider whether, how, and where fossils and isotopic biosignatures could have been preserved in the depositional environments and mineralizing media thought to have been present in habitable settings on early Mars. We conclude that Noachian‐Hesperian Fe‐bearing clay‐rich fluvio‐lacustrine siliciclastic deposits, especially where enriched in silica, currently represent the most promising and best understood astropaleontological targets. Siliceous sinters would also be an excellent target, but their presence on Mars awaits confirmation. More work is needed to improve our understanding of fossil preservation in the context of other environments specific to Mars, particularly within evaporative salts and pore/fracture‐filling subsurface minerals.
Plain Language Summary
This paper reviews the rocks and minerals on Mars that could potentially host fossils or other signs of ancient life preserved since Mars was warmer and wetter billions of years ago. We apply recent results from the study of Earth's fossil record and fossilization processes, and from the geological exploration of Mars by rovers and orbiters, in order to select the most favoured targets for astrobiological missions to Mars. We conclude that mudstones rich in silica and iron‐bearing clays currently offer the best hope of finding fossils on Mars and should be prioritized, but that several other options warrant further research. We also recommend further experimental work on how fossilization processes operate under conditions analogous to early Mars.
Key Points
Noachian‐Hesperian Fe‐bearing clay‐rich fluvio‐lacustrine siliciclastic sediments are favored in the search for ancient Martian life
There is insufficient confidence in the nature of reported silica sinters on Mars or the possibility of preservation in the deep biosphere
Experimental taphonomy approaches from paleontology should now be adapted to understand limits on preservation under Martian conditions
The resistant ~50 m thick Vera Rubin ridge (VRR) situated near the base of Mount Sharp, Gale crater, Mars, has been deemed a high priority science target for the Mars Science Laboratory mission. This ...is because of (1) its position at the base of the 5 km layered strata of Mount Sharp and (2) the detection of hematite from orbit, indicating that it could be the site of enhanced oxidation. The compositional data acquired by the Alpha Particle X‐ray Spectrometer (APXS) during Curiosity's exploration of VRR help to elucidate questions pertaining to the formation of the ridge. APXS analyses indicate that VRR falls within the compositional range of underlying lacustrine mudstones, consistent with a continuation of that depositional environment and derivation from a similar provenance. Lower Fe concentrations for VRR compared to the underlying strata discounts the addition of large amounts of hematite to the strata, either as cement or as detrital input. Compositional trends are associated with VRR cross‐cut stratigraphy, indicating postdepositional processes. Higher Si and Al and lower Ti, Fe, and Mn than the underlying mudstone, particularly within distinct patches of gray/blue bedrock, are consistent with the addition of Si and Al. Lateral and vertical compositional variations suggest enhanced element mobility and fluid flow (possibly via multiple events) through VRR, increasing toward the top of the ridge, consistent with the action of warm (~50–100°C), locally acidic saline fluids as inferred from the mineralogy of drilled samples.
Plain Language Summary
Curiosity has explored the resistant Vera Rubin ridge (VRR) at the base of Mount Sharp, Gale crater, Mars, owing to (1) its position within the 5 km layered rocks of Mount Sharp, which record changes in Mars environment through time, and (2) the detection of hematite from orbit. The Alpha Particle X‐ray Spectrometer (APXS) measures the elemental composition of rocks. APXS analyses indicate that VRR has a similar composition to underlying mudstones, consistent with continued deposition in a lake. Lower iron discounts the addition of large amounts of hematite, holding together mineral grains either as cement or as detrital grains. Other elemental trends cut across layering, indicating postdepositional processes. Lateral and vertical compositional variations suggest enhanced element mobility and fluid flow (possibly via multiple events) through VRR, particularly at the top of the ridge and within gray/blue patches of bedrock, consistent with the action of warm (~50–100°C), acidic saline fluids inferred from the mineralogy of drilled samples.
Key Points
Vera Rubin ridge is compositionally a continuation of the Murray formation
Compositional trends cut across stratigraphy, are postdepositional, diagenetic, and/or products of later alteration
APXS data indicate enhanced fluid flow and Si, Al, and Mn mobilization within VRR
Geochemical results are presented from Curiosity's exploration of Vera Rubin ridge (VRR), in addition to the full chemostratigraphy of the predominantly lacustrine mudstone Murray formation up to and ...including VRR. VRR is a prominent ridge flanking Aeolis Mons (informally Mt. Sharp), the central mound in Gale crater, Mars, and was a key area of interest for the Mars Science Laboratory mission. ChemCam data show that VRR is overall geochemically similar to lower‐lying members of the Murray formation, even though the top of VRR shows a strong hematite spectral signature as observed from orbit. Although overall geochemically similar, VRR is characterized by a prominent decrease in Li abundance and Chemical Index of Alteration across the ridge. This decrease follows the morphology of the ridge rather than elevation and is inferred to reflect a nondepositionally controlled decrease in clay mineral abundance in VRR rocks. Additionally, a notable enrichment in Mn above baseline levels is observed on VRR. While not supporting a single model, the results suggest that VRR rocks were likely affected by multiple episodes of postdepositional groundwater interactions that made them more erosionally resistant than surrounding Murray rocks, thus resulting in the modern‐day ridge after subsequent erosion.
Plain Language Summary
Results from the ChemCam instrument on Vera Rubin ridge (VRR) in Gale crater, Mars, are presented and compared with observations from similar rocks leading up to the ridge. VRR is a prominent ridge, flanking the central mound, Aeolis Mons, in Gale crater, Mars. The ridge attracted early attention because it displays strong iron‐oxide spectral signatures. Surprisingly, ChemCam data show that VRR rocks do not show an overall increase in iron abundance relative to the comparable bedrock analyzed for almost 300 m in elevation leading up to the ridge. While similar overall, some notable variations were observed on VRR relative to lower‐lying rocks. In particular, geochemical variations suggest a strong decrease in clay content on the ridge, above which, a notable enrichment in Mn is observed. No single geological process confidently explains all observations on the ridge. Rather, we think that VRR rocks underwent a series of interactions with groundwater that caused the rocks of VRR to become more resistant to erosion than their surroundings, thus emerging as a ridge as the rocks around them eroded. This likely implies that groundwater persisted in Gale crater even long after the disappearance of the ancient lake.
Key Points
A decrease in Li and Chemical Index of Alteration, reflecting clay mineral content, is observed across Vera Rubin ridge (VRR)
A Mn‐rich interval is observed stratigraphically above the decrease in clay mineral content on VRR
VRR likely resulted from increased induration from late‐stage fluid interactions long after the lake environment in Gale crater ceased
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