11,225 research outputs found

    L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling.

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    During nervous system development different cell-to-cell communication mechanisms operate in parallel guiding migrating neurons and growing axons to generate complex arrays of neural circuits. How such a system works in coordination is not well understood. Cross-regulatory interactions between different signalling pathways and redundancy between them can increase precision and fidelity of guidance systems. Immunoglobulin superfamily proteins of the NCAM and L1 families couple specific substrate recognition and cell adhesion with the activation of receptor tyrosine kinases. Thus it has been shown that L1CAM-mediated cell adhesion promotes the activation of the EGFR (erbB1) from Drosophila to humans. Here we explore the specificity of the molecular interaction between L1CAM and the erbB receptor family. We show that L1CAM binds physically erbB receptors in both heterologous systems and the mammalian developing brain. Different Ig-like domains located in the extracellular part of L1CAM can support this interaction. Interestingly, binding of L1CAM to erbB enhances its response to neuregulins. During development this may synergize with the activation of erbB receptors through L1CAM homophilic interactions, conferring diffusible neuregulins specificity for cells or axons that interact with the substrate through L1CAM

    ABCD transfer matrix model of Gaussian beam propagation in plano-concave optical microresonators

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    Plano-concave optical microresonators (PCMRs) are optical microcavities formed of one planar and one concave mirror separated by a spacer. PCMRs illuminated by Gaussian laser beams are used as sensors and filters in fields including quantum electrodynamics, temperature sensing, and photoacoustic imaging. To predict characteristics such as the sensitivity of PCMRs, a model of Gaussian beam propagation through PCMRs based on the ABCD matrix method was developed. To validate the model, interferometer transfer functions (ITFs) calculated for a range of PCMRs and beams were compared to experimental measurements. A good agreement was observed, suggesting the model is valid. It could therefore constitute a useful tool for designing and evaluating PCMR systems in various fields. The computer code implementing the model has been made available online

    Early characterization of the severity and transmissibility of pandemic influenza using clinical episode data from multiple populations

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    The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133-0.150 and R0, 1.09-2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics

    Economic and agronomic impact assessment of wheat straw based alkyl polyglucoside produced using green chemical approaches

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    Results from a previous environmental impact assessment highlight the potential for the proposed process, that converts low-value agricultural residue (wheat straw) into a high-value biosurfactant, to result in significant (>75%) GHG savings, relative to the commercial candidate derived from palm kernel and wheat grain. This was achieved via the use of low-energy techniques like supercritical CO2 extraction, low-temperature microwave and in-situ fractionation of platform chemicals. Despite the environmental benefits, process commercialization relies on the economic feasibility of the production. Adopting a ‘cradle-to-gate’ life cycle costing approach, this paper has quantified the economic feasibility and resource efficiency characteristics of producing wheat-straw based APG, via the previously suggested green low-waste generating processes. Here, we undertook economic analysis of a wheat straw-derived APG production pathway, in comparison to palm-kernel and wheat-grain APG. Total processing costs were determined to range between 0.92−0.92- 1.87 per kg of wheat straw-APG demonstrating relatively better output service quality and energy efficiency, while conventional APG costs 1.95−1.95- 2.87 per kg, highlighting the significant potential of the residue-derived pathway to be scaled to commercial-level. In addition, a semi-quantitative assessment of the demand-based implications of adopting and scaling-up the green process, in the current context and practices of wheat cultivation was also undertaken. Potential agronomic impact that might be result from such scale-up scenarios, focusing on the effect of conventional residue incorporation practiced by farmers was assessed in detail to encourage farmers opt for informed choices and also to encourage both environmentally and economically sustainable systems-thinking

    Rural-to-urban migration and risk of hypertension: longitudinal results of the PERU MIGRANT study.

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    Urbanization can be detrimental to health in populations due to changes in dietary and physical activity patterns. The aim of this study was to determine the effect of migration on the incidence of hypertension. Participants of the PERU MIGRANT study, that is, rural, urban and rural-to-urban migrants, were re-evaluated after 5 years after baseline assessment. The outcome was incidence of hypertension; and the exposures were study group and other well-known risk factors. Incidence rates, relative risks (RRs) and population attributable fractions (PAFs) were calculated. At baseline, 201 (20.4%), 589 (59.5%) and 199 (20.1%) participants were rural, rural-to-urban migrant and urban subjects, respectively. Overall mean age was 47.9 (s.d.±12.0) years, and 522 (52.9%) were female. Hypertension prevalence at baseline was 16.0% (95% confidence interval (CI) 13.7-18.3), being more common in urban group; whereas pre-hypertension was more prevalent in rural participants (P<0.001). Follow-up rate at 5 years was 94%, 895 participants were re-assessed and 33 (3.3%) deaths were recorded. Overall incidence of hypertension was 1.73 (95%CI 1.36-2.20) per 100 person-years. In multivariable model and compared with the urban group, rural group had a greater risk of developing hypertension (RR 3.58; 95%CI 1.42-9.06). PAFs showed high waist circumference as the leading risk factor for the hypertension development in rural (19.1%), migrant (27.9%) and urban (45.8%) participants. Subjects from rural areas are at higher risk of developing hypertension relative to rural-urban migrant or urban groups. Central obesity was the leading risk factor for hypertension incidence in the three population groups

    After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination

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    There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair. Using genetic lineage-tracing and scanning-block face electron microscopy, we show that injury of sciatic nerves from mice of either sex triggers extensive and unexpected Schwann cell elongation and branching to form long, parallel processes. Repair cells are 2- to 3-fold longer than myelin and Remak cells and 7- to 10-fold longer than immature Schwann cells. Remarkably, when repair cells transit back to myelinating cells, they shorten ∼7-fold to generate the typically short internodes of regenerated nerves. The present experiments define novel morphological transitions in injured nerves and show that repair Schwann cells have a cell-type-specific structure that differentiates them from other cells in the Schwann cell lineage. They also provide the first direct evidence using genetic lineage tracing for two basic assumptions in Schwann cell biology: that myelin and Remak cells generate the elongated cells that build Bungner bands in injured nerves and that such cells can transform to myelin cells after regeneration

    Obesity risk in rural, urban and rural-to-urban migrants: prospective results of the PERU MIGRANT study.

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    BACKGROUND: Although migration and urbanization have been linked with higher obesity rates, especially in low-resource settings, prospective information about the magnitude of these effects is lacking. We estimated the risk of obesity and central obesity among rural subjects, rural-to-urban migrants and urban subjects. METHODS: Prospective data from the PERU MIGRANT Study were analyzed. Baseline data were collected in 2007-2008 and participants re-contacted in 2012-2013. At follow-up, outcomes were obesity and central obesity measured by body mass index and waist circumference. At baseline, the primary exposure was demographic group: rural, rural-to-urban migrant and urban. Other exposures included an assets index and educational attainment. Cumulative incidence, incidence ratio (IR) and 95% confidence intervals (95% CI) for obesity and central obesity were estimated with Poisson regression models. RESULTS: At baseline, mean age (±s.d.) was 47.9 (±12.0) years, and 53.0% were females. Rural subjects comprised 20.2% of the total sample, whereas 59.7% were rural-to-urban migrants and 20.1% were urban dwellers. A total of 3598 and 2174 person-years were analyzed for obesity and central obesity outcomes, respectively. At baseline, the prevalence of obesity and central obesity was 20.0 and 52.5%. In multivariable models, migrant and urban groups had an 8- to 9.5-fold higher IR of obesity compared with the rural group (IR migrants=8.19, 95% CI=2.72-24.67; IR urban=9.51, 95% CI=2.74-33.01). For central obesity, there was a higher IR only among the migrant group (IR=1.95; 95% CI=1.22-3.13). Assets index was associated with a higher IR of central obesity (IR top versus bottom tertile 1.45, 95% CI=1.03-2.06). CONCLUSIONS: Peruvian urban individuals and rural-to-urban migrants show a higher incidence of obesity compared with their rural counterparts. Given the ongoing urbanization occurring in middle-income countries, the rapid development of increased obesity risk by rural-to-urban migrants suggests that measures to reduce obesity should be a priority for this group

    IPv6 Multicast Forwarding in RPL-Based Wireless Sensor Networks

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    This article was published in the journal, Wireless Personal Communications [© Springer Science+Business Media] and the definitive version is available at: http://dx.doi.org/10.1007/s11277-013-1250-5In wireless sensor deployments, network layer multicast can be used to improve the bandwidth and energy efficiency for a variety of applications, such as service discovery or network management. However, despite efforts to adopt IPv6 in networks of constrained devices, multicast has been somewhat overlooked. The Multicast Forwarding Using Trickle (Trickle Multicast) internet draft is one of the most noteworthy efforts. The specification of the IPv6 routing protocol for low power and lossy networks (RPL) also attempts to address the area but leaves many questions unanswered. In this paper we highlight our concerns about both these approaches. Subsequently, we present our alternative mechanism, called stateless multicast RPL forwarding algorithm (SMRF), which addresses the aforementioned drawbacks. Having extended the TCP/IP engine of the Contiki embedded operating system to support both trickle multicast (TM) and SMRF, we present an in-depth comparison, backed by simulated evaluation as well as by experiments conducted on a multi-hop hardware testbed. Results demonstrate that SMRF achieves significant delay and energy efficiency improvements at the cost of a small increase in packet loss. The outcome of our hardware experiments show that simulation results were realistic. Lastly, we evaluate both algorithms in terms of code size and memory requirements, highlighting SMRF's low implementation complexity. Both implementations have been made available to the community for adoption
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