Low Reynolds number hydrodynamics of asymmetric, oscillating dumbbell pairs

Active dumbbell suspensions constitute one of the simplest model system for collective swimming at low Reynolds number. Generalizing recent work, we derive and analyze stroke-averaged equations of motion that capture the effective hydrodynamic far-field interaction between two oscillating, asymmetric dumbbells in three space dimensions. Time-averaged equations of motion, as those presented in this paper, not only yield a considerable speed-up in numerical simulations, they may also serve as a starting point when deriving continuum equations for the macroscopic dynamics of multi-swimmer suspensions. The specific model discussed here appears to be particularly useful in this context, since it allows one to investigate how the collective macroscopic behavior is affected by changes in the microscopic symmetry of individual swimmers.Comment: 10 pages, to appear in EPJ Special Topic

Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

Determining the Physical Properties of the B Stars I. Methodology and First Results

We describe a new approach to fitting the UV-to-optical spectra of B stars to model atmospheres and present initial results. Using a sample of lightly reddened stars, we demonstrate that the Kurucz model atmospheres can produce excellent fits to either combined low dispersion IUE and optical photometry or HST FOS spectrophotometry, as long as the following conditions are fulfilled: 1) an extended grid of Kurucz models is employed, 2) the IUE NEWSIPS data are placed on the FOS absolute flux system using the Massa & Fitzpatrick (1999) transformation, and 3) all of the model parameters and the effects of interstellar extinction are solved for simultaneously. When these steps are taken, the temperatures, gravities, abundances and microturbulence velocities of lightly reddened B0-A0 V stars are determined to high precision. We also demonstrate that the same procedure can be used to fit the energy distributions of stars which are reddened by any UV extinction curve which can be expressed by the Fitzpatrick & Massa (1990) parameterization scheme. We present an initial set of results and verify our approach through comparisons with angular diameter measurements and the parameters derived for an eclipsing B star binary. We demonstrate that the metallicity derived from the ATLAS 9 fits to main sequence B stars is essentially the Fe abundance. We find that a near zero microturbulence velocity provides the best-fit to all but the hottest or most luminous stars (where it may become a surrogate for atmospheric expansion), and that the use of white dwarfs to calibrate UV spectrophotometry is valid.Comment: 17 pages, including 2 pages of Tables and 6 pages of Figures. Astrophysical Jounral, in pres

Rare isotope production in statistical multifragmentation

Producing rare isotopes through statistical multifragmentation is investigated using the Mekjian method for exact solutions of the canonical ensemble. Both the initial fragmentation and the the sequential decay are modeled in such a way as to avoid Monte Carlo and thus provide yields for arbitrarily scarce fragments. The importance of sequential decay, exact particle-number conservation and the sensitivities to parameters such as density and temperature are explored. Recent measurements of isotope ratios from the fragmentation of different Sn isotopes are interpreted within this picture.Comment: 10 eps figure

Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

Cygnus X-3 with ISO: investigating the wind

We observed the energetic binary Cygnus X-3 in both quiescent and flaring states between 4 and 16 microns using the ISO satellite. We find that the quiescent source shows the thermal free-free spectrum typical of a hot, fast stellar wind, such as from a massive helium star. The quiescent mass-loss rate due to a spherically symmetric, non-accelerating wind is found to be in the range 0.4-2.9 x 10E-4 solar masses per year, consistent with other infrared and radio observations, but considerably larger than the 10E-5 solar masses per year deduced from both the orbital change and the X-ray column density. There is rapid, large amplitude flaring at 4.5 and 11.5 microns at the same time as enhanced radio and X-ray activity, with the infrared spectrum apparently becoming flatter in the flaring state. We believe non-thermal processes are operating, perhaps along with enhanced thermal emission.Comment: Accepted for publication in MNRAS, 11 pages, 6 figure

Weyl-Underhill-Emmrich quantization and the Stratonovich-Weyl quantizer

Weyl-Underhill-Emmrich (WUE) quantization and its generalization are considered. It is shown that an axiomatic definition of the Stratonovich-Weyl (SW) quantizer leads to severe difficulties. Quantization on the cylinder within the WUE formalism is discussed.Comment: 15+1 pages, no figure

Is age a barrier to chemotherapy? Rates of treatment in older patients with breast, colon or lung cancer in England in 2014: A national registry study

Background Survival from cancer in older patients is poorer in the UK than other countries with similar health systems and wealth possibly due to undertreatment and increased toxicities in this specific population. This population-based observational study describes factors affecting systemic anticancer treatment (SACT) use in older patients in England. Methods We identified patients aged ≥70 with stage II-III breast cancer, stage III colon cancer and stage IIIB-IV non-small cell lung cancer (NSCLC) diagnosed in 2014 from a dataset collected by the National Health Service in England. We used logistic regression to estimate factors affecting likelihood of receiving SACT and performed separate regression analyses for each disease, adjusting for age, gender, stage at diagnosis, pathological features, performance status, Charlson comorbidity index, ethnicity and socioeconomic group. We assessed 2-year overall survival (OS) using Kaplan-Meier method. Case mix adjusted treatment rates and workload volume were calculated at hospital level and presented using funnel plots, stratified by age groups (<70 and ≥70) to allow for assessment of variation between centres. Results 36892 patients were identified: 19879 with stage II-III breast cancer, 5292 with stage III colon cancer and 11721 with stage IIIB-IV NSCLC. Patients over 70 were less likely to receive SACT compared to those aged under 70: breast 11.7% vs 64.6%, p < 0.001; colon 37.4% vs 79%, p < 0.001; NSCLC 33.5% vs 60.2%, p < 0.001. 2-year OS for patients receiving SACT was similar for patients aged ≥70 and <70: breast 91.5% (95% CI: 89.3%-93.2%) vs 96.4% (95% CI: 95.9%-96.7%); colon 84.8% (95% CI: 82.6%-86.8%) vs 88.3% (95% CI: 86.7%-89.8%); NSCLC 16.7% (95% CI: 15.1%-18.4%) vs 19.8% (95%CI: 18.5%-21.1%). Patients receiving SACT had better OS than those untreated. SACT rates varied widely between hospitals after adjusting for case-mix across all ages. Conclusions Our study suggests that several factors affect the likelihood of receiving SACT but after adjusting for these, age remains determinant. Identifying hospitals with significantly lower SACT rates should prompt local review of multidisciplinary team practice