Connectivity effects in the segmental self- and cross-reorientation of unentangled polymer melts

The segmental (bond) rotational dynamics in a polymer melt of unentangled, linear bead-spring chains is studied by molecular dynamics simulations. To single out the connectivity effects, states with limited deviations from the Gaussian behavior of the linear displacement are considered. Both the self and the cross bond-bond correlations with rank ℓ=1,2 are studied in detail. For ℓ=1 the correlation functions are precisely described by expressions involving the correlation functions of the chain modes. Several approximations concerning both the self- and the cross-correlations with ℓ=1,2 are developed and assessed. It is found that the simplified description of the excluded volume static effects derived elsewhere [D. Molin et al., J. Phys.: Condens. Matter 18, 7543 (2006)] well accounts for the short time cross-correlations. It also allows a proper modification of the Rouse theory which provides quantitative account of the intermediate and the long time decay of the rotational correlations with ℓ=1

The effect of local thermal fluctuations on the folding kinetics: a study from the perspective of the nonextensive statistical mechanics

Protein folding is a universal process, very fast and accurate, which works consistently (as it should be) in a wide range of physiological conditions. The present work is based on three premises, namely: ($i$) folding reaction is a process with two consecutive and independent stages, namely the search mechanism and the overall productive stabilization; ($ii$) the folding kinetics results from a mechanism as fast as can be; and ($iii$) at nanoscale dimensions, local thermal fluctuations may have important role on the folding kinetics. Here the first stage of folding process (search mechanism) is focused exclusively. The effects and consequences of local thermal fluctuations on the configurational kinetics, treated here in the context of non extensive statistical mechanics, is analyzed in detail through the dependence of the characteristic time of folding ($\tau$) on the temperature $T$ and on the nonextensive parameter $q$.The model used consists of effective residues forming a chain of 27 beads, which occupy different sites of a $3-$D infinite lattice, representing a single protein chain in solution. The configurational evolution, treated by Monte Carlo simulation, is driven mainly by the change in free energy of transfer between consecutive configurations. ...Comment: 19 pages, 3 figures, 1 tabl

Proteins to Order Use of Synthetic DNA to Generate Site-Specific Mutations

The ability to cause specific changes in the amino acid sequences of proteins would greatly advance studies on the influence of protein structure on biochemical function. If the desired changes can once be made in the nucleic acid which encodes the protein, one can use cloning in an appropriate microorganism to produce essentially limitless quantities of the mutant protein. We describe here the application of oligonucleotide-directed site-specific mutagenesis to accomplish this objective for the enzyme B-lactamase, the gene for which is contained in the plasmid pBR322. The method uses a procedure to screen for mutant clones which depends on the DNA in the various colonies and not on the properties of the mutant protein; the method can, therefore, be widely applied and does not require, in each separate case, the development of a screening procedure which depends on some phenotypic difference between mutant and wild-type protein

Enhancing radiological monitoring of 137Cs in coastal environments using taxonomic signals in brown seaweeds

With the rapidly expanding global nuclear industry, more efficient and direct radiological monitoring approaches are needed to ensure the associated environmental health impacts and risk remain fully assessed and undertaken as robustly as possible. Conventionally, radiological monitoring in the environment consists of measuring a wide range of anthropogenically enhanced radionuclides present in selected environmental matrices and using generic transfer values for modelling and prediction that are not necessarily suitable in some situations. Previous studies have found links between taxonomy and radionuclide uptake in terrestrial plants and freshwater fish, but the marine context remains relatively unexplored. This preliminary study was aimed at investigating a similar relationship between brown seaweed, an important indicator in radiological monitoring programmes in the marine environment, and Caesium-137, an important radionuclide discharged to the marine environment. A linear mixed model was fitted using REsidual Maximum Likelihood (REML) to activity concentration data collected from literature published worldwide and other databases. The output from REML modelling was adjusted to the International Atomic Energy Agency (IAEA) quoted transfer value for all seaweed taxa in order to produce mean estimate transfer value for each species, which were then analysed by hierarchical ANalysis Of VAriance (ANOVA) based on the taxonomy of brown seaweeds. Transfer value was found to vary between taxa with increasing significance up the taxonomic hierarchy, suggesting a link to evolutionary history. This novel approach enables contextualisation of activity concentration measurements of important marine indicator species in relation to the wider community, allows prediction of unknown transfer values without the need to sample specific species and could, therefore, enhance radiological monitoring by providing accurate, taxon specific transfer values for use in dose assessments and models of radionuclide transfer in the environment

Particulate Matter Air Pollution Exposure, Distance to Road, and Incident Lung Cancer in the Nurses’ Health Study Cohort

Background: A body of literature has suggested an elevated risk of lung cancer associated with particulate matter and traffic-related pollutants. Objective: We examined the relation of lung cancer incidence with long-term residential exposures to ambient particulate matter and residential distance to roadway, as a proxy for traffic-related exposures. Methods: For participants in the Nurses’ Health Study, a nationwide prospective cohort of women, we estimated 72-month average exposures to PM2.5, PM2.5–10, and PM10 and residential distance to road. Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox proportional hazards models were adjusted for potential confounders. Effect modification by smoking status was examined. Results: During 1,510,027 person-years, 2,155 incident cases of lung cancer were observed among 103,650 participants. In fully adjusted models, a 10-μg/m3 increase in 72-month average PM10 [hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14], PM2.5 (HR = 1.06; 95% CI: 0.91, 1.25), or PM2.5–10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively associated with lung cancer. When the cohort was restricted to never-smokers and to former smokers who had quit at least 10 years before, the associations appeared to increase and were strongest for PM2.5 (PM10: HR = 1.15; 95% CI: 1.00, 1.32; PM2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM2.5–10: HR = 1.11; 95% CI: 0.90, 1.37). Results were most elevated when restricted to the most prevalent subtype, adenocarcinomas. Risks with roadway proximity were less consistent. Conclusions: Our findings support those from other studies indicating increased risk of incident lung cancer associated with ambient PM exposures, especially among never- and long-term former smokers. Citation: Puett RC, Hart JE, Yanosky JD, Spiegelman D, Wang M, Fisher JA, Hong B, Laden F. 2014. Particulate matter air pollution exposure, distance to road, and incident lung cancer in the Nurses’ Health Study Cohort. Environ Health Perspect 122:926–932; http://dx.doi.org/10.1289/ehp.130749

On de-bunking “Fake News” in the post-truth era : how to reduce statistical error in research

The authors note with alarm that statistical noise caused by statistical incompetence is beginning to creep into research on cost overrun in public investment projects, contaminating research with work that does not meet basic standards of validity and reliability. The paper gives examples of such work and proposes three heuristics to root out the problem. First, researchers who are not statisticians, or do not have a strong background in statistics, should abstain from doing statistical analysis, and instead rely on more experienced colleagues, preferably professional statisticians. Second, journal referees should clearly state their level of statistical proficiency to journal editors, so these can set the right referee team. Finally, journal editors should make sure that at least one referee is capable of reviewing the statistical and methodological aspects of a paper. The work under review would have benefitted from observing these simple heuristics, as would any work based on statistical analysis.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Transport and Logistic

Loss of Social Behaviours in Populations of Pseudomonas aeruginosa Infecting Lungs of Patients with Cystic Fibrosis

Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing persistent and frequently fatal infections of the lung in patients with cystic fibrosis. Isolates from chronic infections differ from laboratory and environmental strains in a range of traits and this is widely interpreted as the result of adaptation to the lung environment. Typically, chronic strains carry mutations in global regulation factors that could effect reduced expression of social traits, raising the possibility that competitive dynamics between cooperative and selfish, cheating strains could also drive changes in P. aeruginosa infections. We compared the expression of cooperative traits - biofilm formation, secretion of exo-products and quorum sensing (QS) - in P. aeruginosa isolates that were estimated to have spent different lengths of time in the lung based on clinical information. All three exo-products involved in nutrient acquisition were produced in significantly smaller quantities with increased duration of infection, and patterns across four QS signal molecules were consistent with accumulation over time of mutations in lasR, which are known to disrupt the ability of cells to respond to QS signal. Pyocyanin production, and the proportion of cells in biofilm relative to motile, free-living cells in liquid culture, did not change. Overall, our results confirm that the loss of social behaviour is a consistent trend with time spent in the lung and suggest that social dynamics are potentially relevant to understanding the behaviour of P. aeruginosa in lung infections

Aborted propagation of the Ethiopian rift caused by linkage with the Kenyan rift

International audienceContinental rift systems form by propagation of isolated rift segments that interact, and eventually evolve into continuous zones of deformation. This process impacts many aspects of rifting including rift morphology at breakup, and eventual ocean-ridge segmentation. Yet, rift segment growth and interaction remain enigmatic. Here we present geological data from the poorly documented Ririba rift (South Ethiopia) that reveals how two major sectors of the East African rift, the Kenyan and Ethiopian rifts, interact. We show that the Ririba rift formed from the southward propagation of the Ethiopian rift during the Pliocene but this propagation was short-lived and aborted close to the Pliocene-Pleistocene boundary. Seismicity data support the abandonment of laterally offset, overlapping tips of the Ethiopian and Kenyan rifts. Integration with new numerical models indicates that rift abandonment resulted from progressive focusing of the tectonic and magmatic activity into an oblique, throughgoing rift zone of near pure extension directly connecting the rift sectors

TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+ T cells

Background: Nickel is the most frequent cause of T cell-mediated allergic contact dermatitis worldwide. In vitro, CD4+ T cells from all donors respond to nickel but the involved αβ T cell receptor (TCR) repertoire has not been comprehensively analyzed. Methods: We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel-specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Naïve (CCR7+ CD45RA+) and memory (not naïve) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 µmol/L NiSO4 ., TCR α- and β-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing. Results: Stimulation of PBMCs with NiSO4 induced CD154 expression on ~0.1% (mean) of naïve and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased ~13-fold and were associated with markers of in vivo activation. CD154 expression was TCR-mediated since single clones could be specifically restimulated. Among nickel-specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the α-chain segment TRAV9-2 or a histidine in their α- or β-chain complementarity determining region 3 (CDR3) were highly overrepresented. Conclusions: Induced CD154 expression represents a reliable method to study nickel-specific CD4+ T cells. TCRs with particular features respond in all donors, while strongly increased blood frequencies indicate nickel allergy for some donors. Our approach may be extended to other contact allergens for the further development of diagnostic and predictive in vitro tests