151 research outputs found
Quantitative analyses of empirical fitness landscapes
The concept of a fitness landscape is a powerful metaphor that offers insight
into various aspects of evolutionary processes and guidance for the study of
evolution. Until recently, empirical evidence on the ruggedness of these
landscapes was lacking, but since it became feasible to construct all possible
genotypes containing combinations of a limited set of mutations, the number of
studies has grown to a point where a classification of landscapes becomes
possible. The aim of this review is to identify measures of epistasis that
allow a meaningful comparison of fitness landscapes and then apply them to the
empirical landscapes to discern factors that affect ruggedness. The various
measures of epistasis that have been proposed in the literature appear to be
equivalent. Our comparison shows that the ruggedness of the empirical landscape
is affected by whether the included mutations are beneficial or deleterious and
by whether intra- or intergenic epistasis is involved. Finally, the empirical
landscapes are compared to landscapes generated with the Rough Mt.\ Fuji model.
Despite the simplicity of this model, it captures the features of the
experimental landscapes remarkably well.Comment: 24 pages, 5 figures; to appear in Journal of Statistical Mechanics:
Theory and Experimen
Electron rescattering at metal nanotips induced by ultrashort laser pulses
We report on the first investigation of plateau and cut-off structures in
photoelectron spectra from nano-scale metal tips interacting with few-cycle
near-infrared laser pulses. These hallmarks of electron rescattering,
well-known from atom-laser interaction in the strong-field regime, appear at
remarkably low laser intensities with nominal Keldysh parameters of the order
of . Quantum and quasi-classical simulations reveal that a large
field enhancement near the tip and the increased backscattering probability at
a solid-state target play a key role. Plateau electrons are by an order of
magnitude more abundant than in comparable atomic spectra, reflecting the high
density of target atoms at the surface. The position of the cut-off serves as
an in-situ probe for the locally enhanced electric field at the tip apex
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Online single particle analysis of ice particle residuals from mountain-top mixed-phase clouds using laboratory derived particle type assignment
In situ single particle analysis of ice particle residuals (IPRs) and out-of-cloud aerosol particles was conducted by means of laser ablation mass spectrometry during the intensive INUIT-JFJ/CLACE campaign at the high alpine research station Jungfraujoch (3580âŻmâŻa.s.l.) in JanuaryâFebruary 2013. During the 4-week campaign more than 70âŻ000 out-of-cloud aerosol particles and 595 IPRs were analyzed covering a particle size diameter range from 100âŻnm to 3âŻÂľm. The IPRs were sampled during 273âŻh while the station was covered by mixed-phase clouds at ambient temperatures between â27 and â6âŻÂ°C. The identification of particle types is based on laboratory studies of different types of biological, mineral and anthropogenic aerosol particles. The outcome of these laboratory studies was characteristic marker peaks for each investigated particle type. These marker peaks were applied to the field data. In the sampled IPRs we identified a larger number fraction of primary aerosol particles, like soil dust (13âŻÂąâŻ5âŻ%) and minerals (11âŻÂąâŻ5âŻ%), in comparison to out-of-cloud aerosol particles (2.4âŻÂąâŻ0.4 and 0.4âŻÂąâŻ0.1âŻ%, respectively). Additionally, anthropogenic aerosol particles, such as particles from industrial emissions and lead-containing particles, were found to be more abundant in the IPRs than in the out-of-cloud aerosol. In the out-of-cloud aerosol we identified a large fraction of aged particles (31âŻÂąâŻ5âŻ%), including organic material and secondary inorganics, whereas this particle type was much less abundant (2.7âŻÂąâŻ1.3âŻ%) in the IPRs. In a selected subset of the data where a direct comparison between out-of-cloud aerosol particles and IPRs in air masses with similar origin was possible, a pronounced enhancement of biological particles was found in the IPRs
A mock circulation loop to test extracorporeal CO2 elimination setups
Background: Extracorporeal carbon dioxide removal (ECCO2R) is a promising yet
limited researched therapy for hypercapnic respiratory failure in acute respiratory
distress syndrome and exacerbated chronic obstructive pulmonary disease. Herein,
we describe a new mock circuit that enables experimental ECCO2R research without
animal models. In a second step, we use this model to investigate three experimental
scenarios of ECCO2R: (I) the influence of hemoglobin concentration on CO2 removal. (II)
a potentially portable ECCO2R that uses air instead of oxygen, (III) a low-flow ECCO2R
that achieves effective CO2 clearance by recirculation and acidification of the limited
blood volume of a small dual lumen cannula (such as a dialysis catheter).
Results: With the presented ECCO2R mock, CO2 removal rates comparable to previous
studies were obtained. The mock works with either fresh porcine blood or diluted
expired human packed red blood cells. However, fresh porcine blood was preferred
because of better handling and availability. In the second step of this work, hemoglobin
concentration was identified as an important factor for CO2 removal. In the second
scenario, an air-driven ECCO2R setup showed only a slightly lower CO2 wash-out than the
same setup with pure oxygen as sweep gas. In the last scenario, the low-flow ECCO2R,
the blood flow at the test membrane lung was successfully raised with a recirculation
channel without the need to increase cannula flow. Low recirculation ratios resulted in
increased efficiency, while high recirculation ratios caused slightly reduced CO2 removal
rates. Acidification of the CO2 depleted blood in the recirculation channel caused an
increase in CO2 removal rate.
Conclusions: We demonstrate a simple and cost effective, yet powerful, âin-vitroâ
ECCO2R model that can be used as an alternative to animal experiments for many
research scenarios. Moreover, in our approach parameters such as hemoglobin level can
be modified more easily than in animal models
Quantifying the Adaptive Potential of an Antibiotic Resistance Enzyme
For a quantitative understanding of the process of adaptation, we need to understand its âraw material,â that is, the frequency and fitness effects of beneficial mutations. At present, most empirical evidence suggests an exponential distribution of fitness effects of beneficial mutations, as predicted for Gumbel-domain distributions by extreme value theory. Here, we study the distribution of mutation effects on cefotaxime (Ctx) resistance and fitness of 48 unique beneficial mutations in the bacterial enzyme TEM-1 β-lactamase, which were obtained by screening the products of random mutagenesis for increased Ctx resistance. Our contributions are threefold. First, based on the frequency of unique mutations among more than 300 sequenced isolates and correcting for mutation bias, we conservatively estimate that the total number of first-step mutations that increase Ctx resistance in this enzyme is 87 [95% CI 75â189], or 3.4% of all 2,583 possible base-pair substitutions. Of the 48 mutations, 10 are synonymous and the majority of the 38 non-synonymous mutations occur in the pocket surrounding the catalytic site. Second, we estimate the effects of the mutations on Ctx resistance by determining survival at various Ctx concentrations, and we derive their fitness effects by modeling reproduction and survival as a branching process. Third, we find that the distribution of both measures follows a FrĂŠchet-type distribution characterized by a broad tail of a few exceptionally fit mutants. Such distributions have fundamental evolutionary implications, including an increased predictability of evolution, and may provide a partial explanation for recent observations of striking parallel evolution of antibiotic resistance
A participatory parent-focused intervention promoting physical activity in preschools: design of a cluster-randomized trial
<p>Abstract</p> <p>Background</p> <p>With rates of childhood obesity increasing, physical activity (PA) promotion especially in young children has assumed greater importance. Given the limited effectiveness of most interventions to date, new approaches are needed. The General Systems theory suggests that involving parents as intervention targets may be effective in fostering healthier life styles in children. We describe the development of a parent-focused participatory intervention and the procedures used to evaluate its effectiveness in increasing daily PA in preschoolers.</p> <p>Methods/Design</p> <p>Thirty-seven South German preschools were identified for this study and agreed to participate. Using a two-armed, controlled cluster-randomized trial design we test a participatory intervention with parents as the primary target group and potential agents of behavioural change. Specifically, the intervention is designed to engage parents in the development, refinement and selection of project ideas to promote PA and in incorporating these ideas into daily routines within the preschool community, consisting of children, teachers and parents. Our study is embedded within an existing state-sponsored programme providing structured gym lessons to preschool children. Thus, child-based PA outcomes from the study arm with the parent-focused intervention and the state-sponsored programme are compared with those from the study arm with the state-sponsored programme alone. The evaluation entails baseline measurements of study outcomes as well as follow-up measurements at 6 and 12 months. Accelerometry measures PA intensity over a period of six days, with the mean over six days used as the primary outcome measure. Secondary outcomes include childrens' BMI, a sum of averaged skin fold thickness measurements across multiple sites, and PA behaviour. Longitudinal multilevel models are used to assess within-subject change and between-group differences in study outcomes, adjusted for covariates at the preschool and individual levels. Teacher qualitative interviews monitor the intervention implementation process.</p> <p>Discussion</p> <p>Participatory approaches that actively involve parents have the potential to promote PA in ways that might be better tailored to local needs and more sustainable. Our mixed methods approach to assess the intervention efficacy and implementation employing both quantitative and qualitative measures within a cluster-randomized controlled trial may serve as a framework for evaluating public health interventions in preschool settings.</p> <p>Trial Registration</p> <p><b>clinicaltrials.gov No: NCT00987532</b></p
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