Importance of Tree-and Species-Level Interactions with Wildfire, Climate, and Soils in Interior Alaska: Implications for Forest Change Under a Warming Climate

The boreal zone of Alaska is dominated by interactions between disturbances, vegetation, and soils. These interactions are likely to change in the future through increasing permafrost thaw, more frequent and intense wildfires, and vegetation change from drought and competition. We utilize an individual tree-based vegetation model, the University of Virginia Forest Model Enhanced (UVAFME), to estimate current and future forest conditions across sites within interior Alaska. We updated UVAFME for application within interior Alaska, including improved simulation of permafrost dynamics, litter decay, nutrient dynamics, fire mortality, and postfire regrowth. Following these updates, UVAFME output on species-specific biomass and stem density was comparable to inventory measurements at various forest types within interior Alaska. We then simulated forest response to climate change at specific inventory locations and across the Tanana Valley River Basin on a 2 × 2 km2 grid. We derived projected temperature and precipitation from a five-model average taken from the CMIP5 archive under the RCP 4.5 and 8.5 scenarios. Results suggest that climate change and the concomitant impacts on wildfire and permafrost dynamics will result in overall decreases in biomass (particularly for spruce (Picea spp.)) within the interior Tanana Valley, despite increases in quaking aspen (Populus tremuloides) biomass, and a resulting shift towards higher deciduous fraction. Simulation results also predict increases in biomass at cold, wet locations and at high elevations, and decreases in biomass in dry locations, under both moderate (RCP 4.5) and extreme (RCP 8.5) climate change scenarios. These simulations demonstrate that a highly detailed, species interactive model can be used across a large region within Alaska to investigate interactions between vegetation, climate, wildfire, and permafrost. The vegetation changes predicted here have the capacity to feed back to broader scale climate-forest interactions in the North American boreal forest, a region which contributes significantly to the global carbon and energy budgets

Mapping our Universe in 3D with MITEoR

Mapping our universe in 3D by imaging the redshifted 21 cm line from neutral hydrogen has the potential to overtake the cosmic microwave background as our most powerful cosmological probe, because it can map a much larger volume of our Universe, shedding new light on the epoch of reionization, inflation, dark matter, dark energy, and neutrino masses. We report on MITEoR, a pathfinder low-frequency radio interferometer whose goal is to test technologies that greatly reduce the cost of such 3D mapping for a given sensitivity. MITEoR accomplishes this by using massive baseline redundancy both to enable automated precision calibration and to cut the correlator cost scaling from N^2 to NlogN, where N is the number of antennas. The success of MITEoR with its 64 dual-polarization elements bodes well for the more ambitious HERA project, which would incorporate many identical or similar technologies using an order of magnitude more antennas, each with dramatically larger collecting area.Comment: To be published in proceedings of 2013 IEEE International Symposium on Phased Array Systems & Technolog

Accelerated aging of skeletal muscle and the immune system in patients with chronic liver disease

Patients with chronic liver disease (CLD) often present with significant frailty, sarcopenia, and impaired immune function. However, the mechanisms driving the development of these age-related phenotypes are not fully understood. To determine whether accelerated biological aging may play a role in CLD, epigenetic, transcriptomic, and phenotypic assessments were performed on the skeletal muscle tissue and immune cells of CLD patients and age-matched healthy controls. Accelerated biological aging of the skeletal muscle tissue of CLD patients was detected, as evidenced by an increase in epigenetic age compared with chronological age (mean +2.2 ± 4.8 years compared with healthy controls at −3.0 ± 3.2 years, p = 0.0001). Considering disease etiology, age acceleration was significantly greater in both the alcohol-related (ArLD) (p = 0.01) and nonalcoholic fatty liver disease (NAFLD) (p = 0.0026) subgroups than in the healthy control subgroup, with no age acceleration observed in the immune-mediated subgroup or healthy control subgroup (p = 0.3). The skeletal muscle transcriptome was also enriched for genes associated with cellular senescence. Similarly, blood cell epigenetic age was significantly greater than that in control individuals, as calculated using the PhenoAge (p &lt; 0.0001), DunedinPACE (p &lt; 0.0001), or Hannum (p = 0.01) epigenetic clocks, with no difference using the Horvath clock. Analysis of the IMM-Age score indicated a prematurely aged immune phenotype in CLD patients that was 2-fold greater than that observed in age-matched healthy controls (p &lt; 0.0001). These findings suggested that accelerated cellular aging may contribute to a phenotype associated with advanced age in CLD patients. Therefore, therapeutic interventions to reduce biological aging in CLD patients may improve health outcomes.</p

Separation of rare gases and chiral molecules by selective binding in porous organic cages

The separation of molecules with similar size and shape is an important technological challenge. For example, rare gases can pose either an economic opportunity or an environmental hazard and there is a need to separate these spherical molecules selectively at low concentrations in air. Likewise, chiral molecules are important building blocks for pharmaceuticals, but chiral enantiomers, by definition, have identical size and shape, and their separation can be challenging. Here we show that a porous organic cage molecule has unprecedented performance in the solid state for the separation of rare gases, such as krypton and xenon. The selectivity arises from a precise size match between the rare gas and the organic cage cavity, as predicted by molecular simulations. Breakthrough experiments demonstrate real practical potential for the separation of krypton, xenon and radon from air at concentrations of only a few parts per million. We also demonstrate selective binding of chiral organic molecules such as 1-phenylethanol, suggesting applications in enantioselective separation

Separation of rare gases and chiral molecules by selective binding in porous organic cages

The separation of molecules with similar size and shape is an important technological challenge. For example, rare gases can pose either an economic opportunity or an environmental hazard and there is a need to separate these spherical molecules selectively at low concentrations in air. Likewise, chiral molecules are important building blocks for pharmaceuticals, but chiral enantiomers, by definition, have identical size and shape, and their separation can be challenging. Here we show that a porous organic cage molecule has unprecedented performance in the solid state for the separation of rare gases, such as krypton and xenon. The selectivity arises from a precise size match between the rare gas and the organic cage cavity, as predicted by molecular simulations. Breakthrough experiments demonstrate real practical potential for the separation of krypton, xenon and radon from air at concentrations of only a few parts per million. We also demonstrate selective binding of chiral organic molecules such as 1-phenylethanol, suggesting applications in enantioselective separation

Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC The Phase 2 CONDOR Randomized Clinical Trial

IMPORTANCE: Dual blockade of programmed death ligand 1(PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression. OBJECTIVE :To assess safety and objective response rate of durvalumab combined with tremelimumab. DESIGN, SETTING, AND PARTICIPANTS: The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1-low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific. INTERVENTIONS: Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy. MAIN OUTCOMES AND MEASURES: Safety and tolerability and efficacy measured by objective response rate. RESULTS: Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%1339%) in the combination arm (n =129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively. CONCLUSIONS AND RELEVANCE: In patients with R/M HNSCC and low or no PD-Lt tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way

TOI-431/HIP 26013: A super-Earth and a sub-Neptune transiting a bright, early K dwarf, with a third RV planet

We present the bright (Vmag = 9.12), multiplanet system TOI-431, characterized with photometry and radial velocities (RVs). We estimate the stellar rotation period to be 30.5 ± 0.7 d using archival photometry and RVs. Transiting Exoplanet Survey Satellite (TESS) objects of Interest (TOI)-431 b is a super-Earth with a period of 0.49 d, a radius of 1.28 ± 0.04 R, a mass of 3.07 ± 0.35 M, and a density of 8.0 ± 1.0 g cm-3; TOI-431 d is a sub-Neptune with a period of 12.46 d, a radius of 3.29 ± 0.09 R, a mass of 9.90+1.53-1.49 M, and a density of 1.36 ± 0.25 g cm-3. We find a third planet, TOI-431 c, in the High Accuracy Radial velocity Planet Searcher RV data, but it is not seen to transit in the TESS light curves. It has an Msin i of 2.83+0.41-0.34 M, and a period of 4.85 d. TOI-431 d likely has an extended atmosphere and is one of the most well-suited TESS discoveries for atmospheric characterization, while the super-Earth TOI-431 b may be a stripped core. These planets straddle the radius gap, presenting an interesting case-study for atmospheric evolution, and TOI-431 b is a prime TESS discovery for the study of rocky planet phase curves.Fil: Osborn, Ares. University of Warwick; Reino UnidoFil: Armstrong, David J. University of Warwick; Reino UnidoFil: Cale, Bryson. George Mason University; Estados UnidosFil: Brahm, Rafael. Universidad Adolfo Ibañez; Chile. Instituto de Astrofísica; ChileFil: Wittenmyer, Robert A. University Of Southern Queensland; AustraliaFil: Dai, Fei. Division Of Geological And Planetary Sciences; Estados UnidosFil: Crossfield, Ian J. M. University of Kansas; Estados UnidosFil: Bryant, Edward M. University of Warwick; Reino UnidoFil: Adibekyan, Vardan. Universidad de Porto; PortugalFil: Cloutier, Ryan. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Collins, Karen A. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Delgado Mena, E.. Universidad de Porto; PortugalFil: Fridlund, Malcolm. Leiden University; Países Bajos. Chalmers University of Technology; SueciaFil: Hellier, Coel. Keele University; Reino UnidoFil: Howell, Steve B. NASA Ames Research Center; Estados UnidosFil: King, George W. University of Warwick; Reino UnidoFil: Lillo Box, Jorge. Consejo Superior de Investigaciones Científicas. Centro de Astrobiología; EspañaFil: Otegi, Jon. Universidad de Ginebra; Suiza. Universitat Zurich; SuizaFil: Sousa, S.. Universidad de Porto; PortugalFil: Stassun, Keivan G. Vanderbilt University; Estados UnidosFil: Matthews, Elisabeth C. Universidad de Ginebra; Suiza. Massachusetts Institute of Technology; Estados UnidosFil: Ziegler, Carl. University of Toronto; CanadáFil: Ricker, George. Massachusetts Institute of Technology; Estados UnidosFil: Vanderspek, Roland. Massachusetts Institute of Technology; Estados UnidosFil: Latham, David W. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Seager, S.. Massachusetts Institute of Technology; Estados UnidosFil: Winn, Joshua N.. University of Princeton; Estados UnidosFil: Jenkins, Jon M. NASA Ames Research Center; Estados UnidosFil: Acton, Jack S. University of Leicester; Reino UnidoFil: Addison, Brett C. University Of Southern Queensland; AustraliaFil: Diaz, Rodrigo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentin