Explore the vast range of titles available.

The recent advent of nontraditional isotopic systems has revealed that meteorites display a fundamental isotopic dichotomy between noncarbonaceous (NC) and carbonaceous (C) groups, which represent material from the inner and outer solar system, respectively. On the basis of iron isotope anomalies, this view has recently been challenged in favor of a circumsolar disk structured into three distinct reservoirs (the so-called isotopic trichotomy). In this scenario, the CI chondrites—a rare type of carbonaceous chondrites with chemical composition similar to that of the Sun’s photosphere—would sample a distinct source region than other carbonaceous chondrites, located beyond Saturn’s orbit. Here, we report a model based on the available data for both mass-dependent fractionation of Te stable isotopes and mass-independent Fe nucleosynthetic anomalies. On the basis of the Te–Fe isotopic correlation defined by all carbonaceous chondrites including CIs, we show that the NC-CC dichotomy extends to Fe isotopes. Our finding thus supports (i) the existence of only two reservoirs in the early solar system and (ii) the ubiquitous presence of CI-like dust throughout the carbonaceous reservoir. Our approach also reveals that the carrier phase of 54Fe anomalies corresponds to Fe–Ni metal beads mostly located within chondrules. Finally, we propose that the CC chondrule component records a constant mix of refractory inclusions and NC-like dust.

BackgroundNon-alcoholic fatty liver disease is an obesity-related chronic liver disorder ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis.ObjectiveTto investigate the role of Toll-like receptor (TLR) 4 in mediating the transition from steatosis to inflammation.MethodsApoE−/−/TLR4mut mice and ApoE−/−/TLR4 wild-type mice (ApoE−/−/TLR4-WT) were generated by cross-breeding an ApoE-deficient (ApoE−/−) strain with TLR4-mutant (TLR4mut) mice, which were fed with high-fat, high-cholesterol (HFHC) diet to induce obesity.ResultsApoE−/−/TLR4-WT mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH, which is associated with obesity and the metabolic syndrome. By contrast, ApoE−/−/TLR4mut mice lacking functional TLR4 were resistant to HFHC diet-induced liver inflammation and injury and were less susceptible to the diet-induced production of reactive oxygen species (ROS) and proinflammatory cytokines. In ApoE−/−/TLR4-WT mice, X-box binding protein-1 (XBP-1), a transcription factor involved in the unfolded protein responses, was activated in the liver by an HFHC diet, whereas XBP-1 activation was abrogated in ApoE−/−/TLR4mut mice. In primary rat Kupffer cells, endotoxin induced XBP-1 activation through ROS production, whereas siRNA-mediated knockdown of XBP-1 expression resulted in a marked attenuation in endotoxin-evoked NF-κB activation and cytokine production. Furthermore, adenovirus-mediated expression of dominant negative XBP-1 led to a significant attenuation in HFHC diet-induced liver inflammation and injury in mice.ConclusionsThese findings support the key role of TLR4 in Kupffer cells in mediating the progression of simple steatosis to NASH, by inducing ROS-dependent activation of XBP-1.

Purpose MDM2 and CDK4 are frequently co-amplified in well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). We aimed to determine whether combined MDM2/CDK4 targeting is associated with higher antitumour activity than a single agent in preclinical models of DDLPS. Experimental design DDLPS cells were exposed to RG7388 (MDM2 antagonist) and palbociclib (CDK4 inhibitor), and apoptosis and signalling/survival pathway perturbations were monitored by flow cytometry and Western blotting. Xenograft mouse models were used to assess tumour growth and survival. Treatment efficacy was assessed by Western blotting, histopathology and tumour volume. Results RG7388 and palbociclib together exerted a greater antitumour effect than either drug alone, with significant differences in cell viability after a 72-h treatment with RG7388 and/or palbociclib. The combination treatment significantly increased apoptosis compared to the single agents. We then analysed the in vivo antitumour activity of RG7388 and palbociclib in a xenograft model of DDLPS. The combination regimen reduced the tumour growth rate compared with a single agent alone and significantly increased the median progression-free survival. Conclusions Our results provide a strong rationale for evaluating the therapeutic potential of CDK4 inhibitors as potentiators of MDM2 antagonists in DDLPS and justify clinical trials in this setting.

Ground-based observations of “Barbarian” L-type asteroids at 1–2.5 μm indicate that their near-infrared spectra are dominated by the mineral spinel, which has been attributed to a high abundance of calcium-aluminum inclusions (CAIs)—the first solids to condense out of the protoplanetary disk during the formation of the solar system. However, the spectral properties of these asteroids from 2.5–5 μm, a wavelength region that covers signatures of hydrated minerals, water, and organics, have not yet been explored. Here, we present 2–5 μm reflectance spectra of five spinel-rich asteroids obtained with the NIRSpec instrument on the James Webb Space Telescope. All five targets exhibit a ∼2.85 μm absorption feature with a band depth of 3%–6% that appears correlated in strength with that of the 2 μm spinel absorption feature. The shape and position of the 2.85 μm feature are not a good match to the 2.7 μm feature commonly seen in carbonaceous CM meteorites or C-type asteroids. The closest spectral matches are to the Moon and Vesta, suggesting commonalities in aqueous alteration across silicate bodies, infall of hydrated material, and/or space weathering by solar wind H implantation. Lab spectra of CO/CV chondrites, CAIs, as well as the minerals cronstedtite and spinel, also show a similar feature, providing clues into the origin of the 2.85 μm feature.

We present analyses of mass-dependent isotope fractionation of strontium (Sr) and neodymium (Nd) from a number of petrologically and chemically diverse calcium–aluminium-rich inclusions (CAIs) from the CV chondrite Allende. Combined with literature data, our results reveal systematic variations of elemental and isotopic fractionation signatures that depend on element volatility and CAI type. In most CAIs with little volatility-driven elemental fractionation (which we collectively refer to as “nongroup-II” CAIs), moderately refractory elements such as Nd and Ti are not isotopically fractionated relative to chondrites, while less refractory elements such as Sr and Ca show light isotope enrichments correlated with their lowered abundances. In contrast, in CAIs with the “group-II” type elemental fractionation pattern, refractory elements show more variable isotopic compositions uncorrelated to element abundances. The coupled elemental and isotopic fractionation in nongroup-II CAIs are consistent with a simple evaporation–condensation–reevaporation origin in the solar nebula, while group-II CAIs require more extensive and complex thermal processing histories. The disparate thermal evolutions of group-II and nongroup-II CAIs indicate distinct physical conditions in their formation pathways, corresponding to different localities in the protoplanetary disk. Nongroup-II CAIs may represent materials that were more effectively transported between high-temperature and low-temperature disk zones and thus experienced more intensive heating and cooling, while group-II CAIs represent particles that more frequently traversed between those zones but were neither heated nor cooled as thoroughly as the former.

Atmospheric OCS abundances have been retrieved from infrared spectra measured by the Jet Propulsion Laboratory (JPL) MkIV Fourier transform infra-red (FTIR) spectrometer during 24 balloon flights and during nearly 1100 days of ground-based observations since 1985. Our spectral fitting approach uses broad windows to enhance the precision and robustness of the retrievals. Since OCS has a vertical profile similar in shape to that of N2O, and since tropospheric N2O is very stable, we reference the OCS observations to those of N2O, measured simultaneously in the same air mass, to remove the effects of stratospheric transport, allowing a clearer assessment of secular changes in OCS. Balloon measurements reveal less than 5 % change in stratospheric OCS amounts over the past 25 years. Ground-based measurements reveal a springtime peak of tropospheric OCS, followed by a rapid early-summer decrease, similar to the behavior of CO2. This results in a peak-to-peak seasonal cycle of 5–6 % of the total OCS column at northern mid-latitudes. In the long-term tropospheric OCS record, a 5 % decrease is seen from 1990 to 2002, followed by a 5 % increase from 2003 to 2012.

Even though it has been established that a hyetograph's shape affects the results of hydrological simulations, common engineering practice does not always account for this fact. Instead, a single design storm is often considered sufficient for designing a urban drainage system. This study examines the impact that this design paradigm, combined with the uncertainty introduced by subjective choices made during the design process, has on the robustness of a designed system. To do so, we evaluated a set of individual designs created by engineering students using the same Chicago hyetograph as a design storm. We then created ensembles of hyetographs with the same precipitation volume and duration as the Chicago hyetograph and evaluated the designs' hydrological responses. The results showed that designs, which performed equally well for the initial design storm, triggered varying responses for the storms in the ensembles and, consequently, showed different levels of robustness, hinting at a need to adapt the current design approach.

We report measurements of atmospheric C3H8 from analysis of ground-based solar absorption spectra from the Jet Propulsion Laboratory (JPL) MkIV interferometer. Using the strong Q-branch absorption feature at 2967 cm−1, we can measure C3H8 in locations where its abundance is enhanced by proximity to sources (e.g., large natural gas fields, megacities). A case study of MkIV C3H8 measurements from Fort Sumner, New Mexico, shows that amounts are strongly correlated with ethane (C2H6) and with back-trajectories from SE New Mexico and western Texas, where the Permian Basin oil and natural gas field is located. Measurements from JPL, California, also show large C3H8 enhancements on certain days but more correlated with CO than C2H6. From high-altitude balloon-borne MkIV solar occultation measurements, C3H8 was not detected at any altitude (5–40 km) in any of the 25 flights.

We introduce “Class Symbolic Regression” (Class SR), the first framework for automatically finding a single analytical functional form that accurately fits multiple data sets—each realization being governed by its own (possibly) unique set of fitting parameters. This hierarchical framework leverages the common constraint that all the members of a single class of physical phenomena follow a common governing law. Our approach extends the capabilities of our earlier Physical Symbolic Optimization (Φ-SO) framework for symbolic regression, which integrates dimensional analysis constraints and deep reinforcement learning for unsupervised symbolic analytical function discovery from data. Additionally, we introduce the first Class SR benchmark, comprising a series of synthetic physical challenges specifically designed to evaluate such algorithms. We demonstrate the efficacy of our novel approach by applying it to these benchmark challenges and showcase its practical utility for astrophysics by successfully extracting an analytic galaxy potential from a set of simulated orbits approximating stellar streams.

Afforested peatlands account for about 25 % of human-affected peatlands worldwide. In some regions, particularly the British Isles, forest-to-bog conversions are now underway in the hope of increasing carbon storage and restoring original ecosystem functions. In this study, the effects on surface water quality of forest-to-bog restoration in the Flow Country peatlands of northern Scotland were monitored during 15 months. The hydrochemistry of rainwater, resurgence ground water, forestry drainage ditch water, open bog surface water, forestry-influenced loch water and stream water was examined before, during and after felling. The seasonal cycles of biologically active (C, Si, P) and organically complexed (Fe, Al) elements were characterised by major changes in concentration. The felling operations amplified these effects due to (i) the decomposition of felling residues (leaching K and C) and (ii) the disturbance and partial mineralisation of shallow peat soils (releasing P, Fe and Al). Shorter term changes (1–10 days) produced by rainfall events and associated changes in hydrological flow paths controlled the concentrations of Na, Ca, Mg, Mn, and to a lesser extent K and Al. There were significant negative correlations with flow of [K], [Ca] and [Mg] but a positive correlation between stream flow and [Al]. Concentration-flow relationships were not significantly altered by the felling operations because of the relatively low volume of water released from the felled area. Fluctuations in the water table represented another important control of surface water composition. Resurgence waters produced high [Fe] and [Si] values when water table levels were low. These contributions were diluted with runoff and surface soil waters enriched in dissolved organic carbon (DOC) when levels rose. Sequential ultrafiltration revealed that Fe, C and P co-occurred in the >30 kDa molecular weight fraction in constant relative concentrations. Since forest-to-bog restoration raises the water table, it can be anticipated to result initially in more intense flushing of DOC, including the >30 kDa molecular weight fraction where Fe and P co-occur.