A Dynamically Diluted Alignment Model Reveals the Impact of Cell Turnover on the Plasticity of Tissue Polarity Patterns

The polarisation of cells and tissues is fundamental for tissue morphogenesis during biological development and regeneration. A deeper understanding of biological polarity pattern formation can be gained from the consideration of pattern reorganisation in response to an opposing instructive cue, which we here consider by example of experimentally inducible body axis inversions in planarian flatworms. Our dynamically diluted alignment model represents three processes: entrainment of cell polarity by a global signal, local cell-cell coupling aligning polarity among neighbours and cell turnover inserting initially unpolarised cells. We show that a persistent global orienting signal determines the final mean polarity orientation in this stochastic model. Combining numerical and analytical approaches, we find that neighbour coupling retards polarity pattern reorganisation, whereas cell turnover accelerates it. We derive a formula for an effective neighbour coupling strength integrating both effects and find that the time of polarity reorganisation depends linearly on this effective parameter and no abrupt transitions are observed. This allows to determine neighbour coupling strengths from experimental observations. Our model is related to a dynamic $8$-Potts model with annealed site-dilution and makes testable predictions regarding the polarisation of dynamic systems, such as the planarian epithelium.Comment: Preprint as prior to first submission to Journal of the Royal Society Interface. 25 pages, 6 figures, plus supplement (18 pages, contains 1 table and 7 figures). A supplementary movie is available from https://dx.doi.org/10.6084/m9.figshare.c388781

Effect of early Ambroxol treatment on lung functions in mechanically ventilated preterm newborns who subsequently developed a bronchopulmonary dysplasia (BPD)

AbstractIn a randomized trial in 102 preterm newborns with respiratory distress syndrome (RDS) it has been shown that early Ambroxol treatment (30 mg kg−1over the first 5 days) significantly reduces the incidence of RDS-associated complications [bronchopulmonary dysplasia (BPD), intraventricular haemorrhage, post-natal acquired pneumonia]. The aim of the present analysis was to investigate the effect of Ambroxol treatment on lung function in newborns who developed BPD.Respiratory function testing (RFT) was performed immediately after extubation and at day 28. Tidal volume (VT) and respiratory frequency (f) were measured during tidal breathing using the deadspace free flow-through technique. The lung mechanic parameter VT/maxPeswas determined by measuring the maximal oesophageal pressure changes, maxPes, with a catheter tip pressure transducer.In the placebo group 36/50 infants were extubated within the first 28 days of life and 13/36 (36%) developed BPD. In the Ambroxol group 44/52 were extubated and 9/44 (20%) developed BPD. After extubation, RFT showed (i) no statistically significant difference in the ventilatory parameters of either treatment group, (ii) improved (P<0·05) lung mechanics (VT/maxPes) in Ambroxol group compared to controls (9·4±2·7 ml kPa−1vs. 8·1±2·6 ml kPa−1) and (iii) no statistically significant difference in lung function between infants with and without BPD. At day 28 we found (i) no effect of early Ambroxol treatment on lung functions, (ii) significantly (P<0·05) higher f (58·5±11·7 min−1vs. 49·7±10·1 min−1) and significantly (P<0·01) lower VT(9·6±1·9 ml vs. 12·3±2·7 ml) and VT/maxPes(8·9±2·6 ml kPa−1vs. 12·0±2·9 ml kPa−1) in infants with BPD compared to infants without and (iii) these differences are not influenced by early Ambroxol treatment.If the process of BPD development is induced, early Ambroxol treatment has no influence on impaired lung function at day 28

Counterion condensation and effective charge of PAMAM dendrimers

PAMAM dendrimers are used as a model system to investigate the effects of counterion condensation and the effective charge for spherical polyelectrolytes. Because of their amino groups, PAMAM dendrimers are weak polyelectrolytes. Lowering the pH results in an increasing protonation of the amino groups which is monitored via the proton chemical shifts of the adjacent CH2 groups. The effective charge is determined from a combination of diffusion and electrophoresis NMR. The fraction of the charges, which are effective for the interaction with an external electric field or other charges, decreases with increasing generation (size) of the dendrimers

Exhaustive generation of kk-critical H\mathcal H-free graphs

We describe an algorithm for generating all $k$-critical $\mathcal H$-free graphs, based on a method of Ho\`{a}ng et al. Using this algorithm, we prove that there are only finitely many $4$-critical $(P_7,C_k)$-free graphs, for both $k=4$ and $k=5$. We also show that there are only finitely many $4$-critical graphs $(P_8,C_4)$-free graphs. For each case of these cases we also give the complete lists of critical graphs and vertex-critical graphs. These results generalize previous work by Hell and Huang, and yield certifying algorithms for the $3$-colorability problem in the respective classes. Moreover, we prove that for every $t$, the class of 4-critical planar $P_t$-free graphs is finite. We also determine all 27 4-critical planar $(P_7,C_6)$-free graphs. We also prove that every $P_{10}$-free graph of girth at least five is 3-colorable, and determine the smallest 4-chromatic $P_{12}$-free graph of girth five. Moreover, we show that every $P_{13}$-free graph of girth at least six and every $P_{16}$-free graph of girth at least seven is 3-colorable. This strengthens results of Golovach et al.Comment: 17 pages, improved girth results. arXiv admin note: text overlap with arXiv:1504.0697

Targeted analysis of polymorphic loci from low-coverage shotgun sequence data allows accurate genotyping of HLA genes in historical human populations

The highly polymorphic human leukocyte antigen (HLA) plays a crucial role in adaptive immunity and is associated with various complex diseases. Accurate analysis of HLA genes using ancient DNA (aDNA) data is crucial for understanding their role in human adaptation to pathogens. Here, we describe the TARGT pipeline for targeted analysis of polymorphic loci from low-coverage shotgun sequence data. The pipeline was successfully applied to medieval aDNA samples and validated using both simulated aDNA and modern empirical sequence data from the 1000 Genomes Project. Thus the TARGT pipeline enables accurate analysis of HLA polymorphisms in historical (and modern) human populations

A Human-Oriented Term Rewriting System

© Springer Nature Switzerland AG 2019. We introduce a fully automatic system, implemented in the Lean theorem prover, that solves equality problems of everyday mathematics. Our overriding priority in devising the system is that it should construct proofs of equality in a way that is similar to that of humans. A second goal is that the methods it uses should be domain independent. The basic strategy of the system is to operate with a subtask stack: whenever there is no clear way of making progress towards the task at the top of the stack, the program finds a promising subtask, such as rewriting a subterm, and places that at the top of the stack instead. Heuristics guide the choice of promising subtasks and the rewriting process. This makes proofs more human-like by breaking the problem into tasks in the way that a human would. We show that our system can prove equality theorems simply, without having to preselect or orient rewrite rules as in standard theorem provers, and without having to invoke heavy duty tools for performing simple reasoning

a descriptive study on familiarity with, adherence to and trust in the WHO preventive measures

Background Risk communication is a key component of public health interventions during an outbreak. As the coronavirus pandemic unfolded in late 2019, the World Health Organization (WHO) was at the forefront in the development of risk communication strategies. The WHO introduced a range of activities with the purpose of enabling the public to avail verified and timely information on COVID-19 prevention behaviors. Given the various WHO activities to protect the public health during COVID-19, it is important to investigate the extent of familiarity and uptake of the WHO recommendations among the public during the first wave of the pandemic. Methods To do this, we conducted a large-scale Pan-European survey covering around 7500 individuals that are representative of populations from seven European countries, collected online during April 2-April 15, 2020. We use descriptive statistics including proportions and correlations and graphical representations such as bar charts to analyze and display the data. Results Our findings suggest that information from the WHO in the context of COVID-19 is well trusted and acted upon by the public. Overall familiarity and adherence were quite high in most countries. Adherence was higher for social distancing recommendations compared to hygiene measures. Familiarity and adherence were higher among older, female, and highly educated respondents. However, country level heterogeneities were observed in the level of trust in information from the WHO, with countries severely affected by the pandemic reporting lower levels of trust. Conclusion Our findings call for efforts from health authorities to get regular feedback from the public on their familiarity and compliance with recommendations for preventive measures at all stages of the pandemic, to further develop and adapt risk communication as the pandemic evolves.publishersversionpublishe

A Survey of Satisfiability Modulo Theory

Satisfiability modulo theory (SMT) consists in testing the satisfiability of first-order formulas over linear integer or real arithmetic, or other theories. In this survey, we explain the combination of propositional satisfiability and decision procedures for conjunctions known as DPLL(T), and the alternative "natural domain" approaches. We also cover quantifiers, Craig interpolants, polynomial arithmetic, and how SMT solvers are used in automated software analysis.Comment: Computer Algebra in Scientific Computing, Sep 2016, Bucharest, Romania. 201