66 research outputs found

    Time-frequency characterization of femtosecond extreme ultraviolet pulses

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    A measurement of chirp and pulse duration of fifth harmonic of a frequency-doubled Ti:sapphire laser was presented. The photoelectron signal due to cross correlation of harmonics generated by 400 nm blue light and an 800 nm infrared probe pulse, was measured using energy resolved cross-correlation method. Results demonstrated that the technique could be used to characterize the time-frequency behavior of much higher-order harmonics

    Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit

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    Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals

    Time-Frequency Characterization of Femtosecond Extreme Ultraviolet Pulses

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    A measurement of chirp and pulse duration of fifth harmonic of a frequency-doubled Ti:sapphire laser was presented. The photoelectron signal due to cross correlation of harmonics generated by 400 nm blue light and an 800 nm infrared probe pulse, was measured using energy resolved cross-correlation method. Results demonstrated that the technique could be used to characterize the time-frequency behavior of much higher-order harmonics

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1ÎČ, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1ÎČ innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

    Thermal acclimation increases the stability of a predator-prey interaction in warmer environments.

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    Global warming over the next century is likely to alter the energy demands of consumers and thus the strengths of their interactions with their resources. The subsequent cascading effects on population biomasses could have profound effects on food web stability. One key mechanism by which organisms can cope with a changing environment is phenotypic plasticity, such as acclimation to warmer conditions through reversible changes in their physiology. Here, we measured metabolic rates and functional responses in laboratory experiments for a widespread predator-prey pair of freshwater invertebrates, sampled from across a natural stream temperature gradient in Iceland (4-18℃). This enabled us to parameterize a Rosenzweig-MacArthur population dynamical model to study the effect of thermal acclimation on the persistence of the predator-prey pairs in response to warming. Acclimation to higher temperatures either had neutral effects or reduced the thermal sensitivity of both metabolic and feeding rates for the predator, increasing its energetic efficiency. This resulted in greater stability of population dynamics, as acclimation to higher temperatures increased the biomass of both predator and prey populations with warming. These findings indicate that phenotypic plasticity can act as a buffer against the impacts of environmental warming. As a consequence, predator-prey interactions between ectotherms may be less sensitive to future warming than previously expected, but this requires further investigation across a broader range of interacting species

    Finemapping of the arthritis QTL Pia7 reveals co-localization with Oia2 and the APLEC locus.

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    In this study, we sought to determine the effect of the quantitative trait locus Pia7 on arthritis severity. The regulatory locus derived from the arthritis-resistant E3 rat strain was introgressed into the arthritis-susceptibility DA strain through continuous backcrossing. Congenic rats were studied for their susceptibility to experimental arthritis using pristane and adjuvant oil. In addition, cell number and function of various leukocyte populations were analyzed either under naive or stimulated conditions. We found that the minimal congenic fragment of DA.E3-Pia7 rats overlapped with the minimal fragment in DA.PVG-Oia2 congenic rats, which has been positionally cloned to the antigen-presenting lectin-like receptor complex (APLEC) genes. DA.E3-Pia7 congenic rats were protected from both PIA and OIA, but the protection was more pronounced in OIA. In adoptive transfer experiments we observed that the Pia7 locus controlled the priming of arthritogenic T cells and not the effector phase. In addition, Pia7 congenic rats had a significant higher frequency of B cells and granulocytes as well as TNFalpha production after stimulation, indicating a higher activation state of cells of the innate immune system. In conclusion, this study shows that the APLEC locus is a major locus regulating the severity of experimentally induced arthritis in rats.Genes and Immunity advance online publication, 4 March 2010; doi:10.1038/gene.2010.2

    Time-frequency characterization of femtosecond extreme ultraviolet pulses.

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    We present energy-resolved cross-correlation measurements of an extreme ultraviolet (XUV) pulse, generated as the fifth harmonic (15.5 eV) of an intense 80 fs laser pulse centered at 400 nm. Spectrally resolving the cross-correlation signal allows us to characterize the time-dependent frequency of the XUV pulse. We find that the fifth harmonic has a small negative chirp in excess of that predicted by perturbation theory. In addition, by manipulating the chirp of the driving laser we can induce and measure a positive or a negative chirp on the XUV pulse
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