Patterns of Mesenchymal Condensation in a Multiscale, Discrete Stochastic Model

Cells of the embryonic vertebrate limb in high-density culture undergo chondrogenic pattern formation, which results in the production of regularly spaced “islands” of cartilage similar to the cartilage primordia of the developing limb skeleton. The first step in this process, in vitro and in vivo, is the generation of “cell condensations,” in which the precartilage cells become more tightly packed at the sites at which cartilage will form. In this paper we describe a discrete, stochastic model for the behavior of limb bud precartilage mesenchymal cells in vitro. The model uses a biologically motivated reaction–diffusion process and cell-matrix adhesion (haptotaxis) as the bases of chondrogenic pattern formation, whereby the biochemically distinct condensing cells, as well as the size, number, and arrangement of the multicellular condensations, are generated in a self-organizing fashion. Improving on an earlier lattice-gas representation of the same process, it is multiscale (i.e., cell and molecular dynamics occur on distinct scales), and the cells are represented as spatially extended objects that can change their shape. The authors calibrate the model using experimental data and study sensitivity to changes in key parameters. The simulations have disclosed two distinct dynamic regimes for pattern self-organization involving transient or stationary inductive patterns of morphogens. The authors discuss these modes of pattern formation in relation to available experimental evidence for the in vitro system, as well as their implications for understanding limb skeletal patterning during embryonic development

Named Data Networking based File Access for XRootD

We present the design and implementation of a Named Data Networking (NDN) based Open Storage System plug-in for XRootD. This is an important step towards integrating NDN, a leading future internet architecture, with the existing data management systems in CMS. This work outlines the first results of data transfer tests using internal as well as external 100 Gbps testbeds, and compares the NDN-based implementation with existing solutions

Prevalence of Antibodies against Hantaviruses in Serum and Saliva of Adults Living or Working on Farms in Yorkshire, United Kingdom

We acknowledge Clement and colleagues for their comments [1] on our paper [2]. We agree that many controversies are being discussed by the hantavirus community, particularly surrounding the interpretation of serological results and the designation of new species and strains. Within this setting, we are grateful for the opportunity to respond to the key factual and methodological points raised by Clements et al. [...

Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir

Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines

Prescribers or Multidisciplinarians? An Evaluation of Brief Education for General Practitioners on Chronic Pain Management

Purpose Active pain self-management (PSM) for patients with chronic pain is assumed to require multidisciplinary care, leaving prescribing analgesics the most accessible option for general practitioners (GPs). We sought to upskill GPs in multimodalPSM with a harm minimisation approach for any opioid prescribing. Design and Methodology Having developed an educational training resource, a multidisciplinary team delivered the program to attendees at a GP conference in 2017. The educational package comprised pre-readings, a 6-hour interactive, skills-based workshop, and post-workshop resources. The single-group intervention was evaluated with an original and unvalidated pre/post-test (three months) survey of four domains: knowledge; attitudes; utilisation of strategies involving PSM and opioid harm minimization. Paired t-tests were conducted on each domain score and overall, with effect sizes assessed with Cohen’s d. A sensitivity analysis was performed on the data lacking a post-test survey response. Post-survey scores were imputed via chained regression equations, then paired t-tests analyses were conducted on imputed datasets using Rubin's method to pool estimates. FindingsOf 99 participants, 33 returned both surveys for primary analysis. These were combined in the sensitivity analysis with 60 unpaired surveys. Internal consistency was modest (Cronbach’s alpha 0.736). Primary analysis demonstrated significant self-reported improvements in each educational domain with overall score increasing 10.54 points out of 130 (p0.001 Cohen’s d 1.11). Improvements were similar in a sensitivity analysis. Discussion, Limitations and Conclusions This study found that a brief GP educational package may be a viable intervention for facilitating PSM and promoting safer prescribing strategies. Outcomes at three months, from this unvalidated survey instrument, suggest improvements in knowledge, attitudes and self-reported facilitation of PSM and opioid prescribing. As this study did not measure clinician behaviour or patient outcomes objectively, further educational research is indicated to confirm these findings and identify how best to deliver chronic pain management training

Named Data Networking in Climate Research and HEP Applications

The Computing Models of the LHC experiments continue to evolve from the simple hierarchical MONARC[2] model towards more agile models where data is exchanged among many Tier2 and Tier3 sites, relying on both large scale file transfers with strategic data placement, and an increased use of remote access to object collections with caching through CMS's AAA, ATLAS' FAX and ALICE's AliEn projects, for example. The challenges presented by expanding needs for CPU, storage and network capacity as well as rapid handling of large datasets of file and object collections have pointed the way towards future more agile pervasive models that make best use of highly distributed heterogeneous resources. In this paper, we explore the use of Named Data Networking (NDN), a new Internet architecture focusing on content rather than the location of the data collections. As NDN has shown considerable promise in another data intensive field, Climate Science, we discuss the similarities and differences between the Climate and HEP use cases, along with specific issues HEP faces and will face during LHC Run2 and beyond, which NDN could address

Extracellular DNA Promotes Efficient Extracellular Electron Transfer by Pyocyanin in Pseudomonas aeruginosa Biofilms

Redox cycling of extracellular electron shuttles can enable the metabolic activity of subpopulations within multicellular bacterial biofilms that lack direct access to electron acceptors or donors. How these shuttles catalyze extracellular electron transfer (EET) within biofilms without being lost to the environment has been a long-standing question. Here, we show that phenazines mediate efficient EET through interactions with extracellular DNA (eDNA) in Pseudomonas aeruginosa biofilms. Retention of pyocyanin (PYO) and phenazine carboxamide in the biofilm matrix is facilitated by eDNA binding. In vitro, different phenazines can exchange electrons in the presence or absence of DNA and can participate directly in redox reactions through DNA. In vivo, biofilm eDNA can also support rapid electron transfer between redox active intercalators. Together, these results establish that PYO:eDNA interactions support an efficient redox cycle with rapid EET that is faster than the rate of PYO loss from the biofilm

Rat cities and beehive worlds: density and design in the modern city

Nestled among E. M. Forster's careful studies of Edwardian social mores is a short story called "The Machine Stops." Set many years in the future, it is a work of science fiction that imagines all humanity housed in giant high-density cities buried deep below a lifeless surface. With each citizen cocooned in an identical private chamber, all interaction is mediated through the workings of "the Machine," a totalizing social system that controls every aspect of human life. Cultural variety has ceded to rigorous organization: everywhere is the same, everyone lives the same life. So hopelessly reliant is humanity upon the efficient operation of the Machine, that when the system begins to fail there is little the people can do, and so tightly ordered is the system that the failure spreads. At the story's conclusion, the collapse is total, and Forster's closing image offers a condemnation of the world they had built, and a hopeful glimpse of the world that might, in their absence, return: "The whole city was broken like a honeycomb. [⋯] For a moment they saw the nations of the dead, and, before they joined them, scraps of the untainted sky" (2001: 123). In physically breaking apart the city, there is an extent to which Forster is literalizing the device of the broken society, but it is also the case that the infrastructure of the Machine is so inseparable from its social structure that the failure of one causes the failure of the other. The city has-in the vocabulary of present-day engineers-"failed badly.