16 research outputs found

    Searching for a Stochastic Background of Gravitational Waves with LIGO

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    The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is ΩGW<6.5×105\Omega_{\rm GW} < 6.5 \times 10^{-5}. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

    Climate control of terrestrial carbon exchange across biomes and continents

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    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Linking Flux Network Measurements to Continental Scale Simulations: Ecosystem Carbon Dioxide Exchange Capacity under Non-Water-Stressed Conditions

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    This paper examines long-term eddy covariance data from 18 European and 17 North American and Asian forest, wetland, tundra, grassland, and cropland sites under nonwater- stressed conditions with an empirical rectangular hyperbolic light response model and a single layer two light-class carboxylase-based model. Relationships according to ecosystem functional type are demonstrated between empirical and physiological parameters, suggesting linkages between easily estimated parameters and those with greater potential for process interpretation. Relatively sparse documentation of leaf area index dynamics at flux tower sites is found to be a major difficulty in model inversion and flux interpretation. Therefore, a simplification of the physiological model is carried out for a subset of European network sites with extensive ancillary data. The results from these selected sites are used to derive a new parameter and means for comparing empirical and physiologically based methods across all sites, regardless of ancillary data. The results from the European analysis are then compared with results from the other Northern Hemisphere sites and similar relationships for the simplified process-based parameter were found to hold for European, North American, and Asian temperate and boreal climate zones. This parameter is useful for bridging between flux network observations and continental scale spatial simulations of vegetation/atmosphere carbon dioxide exchange

    Is tailored adjuvant treatment for colon cancer possible?

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    High-risk stage II and stage III colon cancers are associated with significant recurrence rates after surgical resection. Adjuvant chemotherapy has demonstrated a significant disease-free and overall survival benefit for patients, even if not helpful for all. Currently, there are limited clinical and molecular markers that can predict response to chemotherapy and clinical outcome in advanced colon cancer. Herein, we review and discuss recent data about the most promising clinicopathologic and molecular factors described thus far and that are of interest in the management of patients with colon cancer.Journal Articleinfo:eu-repo/semantics/publishe

    On the separation of net ecosystem exchange into assimilation and ecosystem respiration: review and improved algorithm

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    This paper discusses the advantages and disadvantages of the different methods that separate net ecosystem exchange (NEE) into its major components, gross ecosystem carbon uptake (GEP) and ecosystem respiration (Reco). In particular, we analyse the effect of the extrapolation of night-time values of ecosystem respiration into the daytime; this is usually done with a temperature response function that is derived from long-term data sets. For this analysis, we used 16 one-year-long data sets of carbon dioxide exchange measurements from European and US-American eddy covariance networks. These sites span from the boreal to Mediterranean climates, and include deciduous and evergreen forest, scrubland and crop ecosystems

    Climate Control of Terrestrial Carbon Exchange across Biomes and Continents

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    Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predicate future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks1, 2. However, knowledge of even the broad relationships between climate and terrestrial CO2 exchange with the atmosphere on yearly to decadal scales remains highly uncertain. Here we present data describing net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 132 unique sites including various ecosystems over 6 continents with a total of 583 site-years. With respect to controlling factors we find two distinct groupings of sites: (1) a temperature-limited group where NEE has an exponential relationship with mean annual temperature; and (2) a dryness-limited group where NEE has an inverse exponential relationship with the dryness index7. A strong latitudinal dependence emerges, with 92% of the temperature-limited sites located above 42oN, and 77% of the dryness-limited sites located below 42oN. The sensitivity of NEE to mean annual temperature breaks down at a threshold value of ~16oC, above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence. Our findings suggest that (1) net ecosystem carbon exchange is highly limited by mean annual temperature at mid- and high-latitudes, and (2) net ecosystem carbon exchange is highly limited by dryness at low latitudes.JRC.H.2-Air and Climat

    Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

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    BackgroundDespite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.MethodsLinkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).ResultsPositive genetic correlation was observed between MD and AD (rg = + 0.47, P = 6.6 × 10 ). AC-quantity showed positive genetic correlation with both AD (rg = + 0.75, P = 1.8 × 10 ) and MD (rg = + 0.14, P = 2.9 × 10 ), while there was negative correlation of AC-frequency with MD (rg = -0.17, P = 1.5 × 10 ) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10 ). There was no evidence for reverse causation.ConclusionThis study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts
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