2,601 research outputs found

    Decentralised Learning MACs for Collision-free Access in WLANs

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    By combining the features of CSMA and TDMA, fully decentralised WLAN MAC schemes have recently been proposed that converge to collision-free schedules. In this paper we describe a MAC with optimal long-run throughput that is almost decentralised. We then design two \changed{schemes} that are practically realisable, decentralised approximations of this optimal scheme and operate with different amounts of sensing information. We achieve this by (1) introducing learning algorithms that can substantially speed up convergence to collision free operation; (2) developing a decentralised schedule length adaptation scheme that provides long-run fair (uniform) access to the medium while maintaining collision-free access for arbitrary numbers of stations

    The diguanylate cyclase AdrA regulates flagellar biosynthesis in Pseudomonas fluorescens F113 through SadB

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    Flagellum mediated motility is an essential trait for rhizosphere colonization by pseudomonads. Flagella synthesis is a complex and energetically expensive process that is tightly regulated. In Pseudomonas fluorescens, the regulatory cascade starts with the master regulatory protein FleQ that is in turn regulated by environmental signals through the Gac/Rsm and SadB pathways, which converge in the sigma factor AlgU. AlgU is required for the expression of amrZ, encoding a FleQ repressor. AmrZ itself has been shown to modulate c-di-GMP levels through the control of many genes encoding enzymes implicated in c-di-GMP turnover. This cyclic nucleotide regulates flagellar function and besides, the master regulator of the flagellar synthesis signaling pathway, FleQ, has been shown to bind c-di-GMP. Here we show that AdrA, a diguanylate cyclase regulated by AmrZ participates in this signaling pathway. Epistasis analysis has shown that AdrA acts upstream of SadB, linking SadB with environmental signaling. We also show that SadB binds c-di-GMP with higher affinity than FleQ and propose that c-di-GMP produced by AdrA modulates flagella synthesis through SadBThis work was supported by funding from MINECO/FEDER EU Grant RTI2018 093991-BI00 to R.R. and M.M. C.M. was funded by a FPI fellowship from MINECO. EB-R was the recipient of fellowships from Fundación Tatiana Pérez de Guzmán el Bueno (Medioambiente 2016) and the FPU program from MECD (FPU16/05513). Short stays of R.R. and C.M. at John Innes Centre were funded by MECD (Salvador de Madariaga and FPU, respectively

    The ASAC Flight Segment and Network Cost Models

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    To assist NASA in identifying research art, with the greatest potential for improving the air transportation system, two models were developed as part of its Aviation System Analysis Capability (ASAC). The ASAC Flight Segment Cost Model (FSCM) is used to predict aircraft trajectories, resource consumption, and variable operating costs for one or more flight segments. The Network Cost Model can either summarize the costs for a network of flight segments processed by the FSCM or can be used to independently estimate the variable operating costs of flying a fleet of equipment given the number of departures and average flight stage lengths

    Presence of susceptible wild strains of Anopheles gambiae in a large industrial palm farm located in Aboisso, South-Eastern of Côte d'Ivoire.

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    The effectiveness of malaria control programmes through implementation of vector control activities is challenged by the emergence of insecticide resistance. In the South-Eastern region of Côte d'Ivoire, where palm oil plantations remain the predominant agricultural crop, the susceptibility of wild Anopheles gambiae sensu lato species is still unknown and thus requires a particular attention. The current study was carried out to address the gap by in-depth characterization of susceptibility level of An. gambiae mosquitoes from Ehania-V1 to WHO-recommended doses of six insecticides belonging to available classes and also to screen a subset for target site mutations and possible inhibition of P450 enzymes. Overall results showed variable resistance profile across WHO-recommended insecticides tested. Mortalities ranged from 8.3% (the lowest mortality was recorded with DDT) to 98% (the highest mortality was recorded with fenitrothion). Importantly, mortality to deltamethrin, an important pyrethroid used in public health for impregnation of mosquito nets was close to 98%, precluding a possible susceptibility to this insecticide, albeit further investigations are required. Pre-exposure of An. gambiae s.l. to PBO did not show any significant variation across insecticides (p = 0.002), although a partial increase was detected for alphacypermethrin and bendiocarb, suggesting a low of activity of cytochrome P450 enzymes (p = 0.277). High frequency of kdr L1014F was recorded in both Anopheles coluzzii (91%) and in An. gambiae (96%), associated with ace-1 (R) G119S mutation at low frequency (<20%). The high mortality rate to deltamethrin, organophosphate and the non-detection of P450 activity in resistance observed in Ehania-V1 appears as a positive outcome for further control strategies as metabolic-based P450 resistance remains major challenge to manage. These results should help the National Malaria Control Programme when designing strategies for vector control in palm oil areas of Côte d'Ivoire

    Structural insights into the mechanism of adaptive ribosomal modification by Pseudomonas RimK

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    Bacteria are equipped with a diverse set of regulatory tools that allow them to quickly adapt to their environment. The RimK system allows for Pseudomonas spp. to adapt through post-transcriptional regulation by altering the ribosomal subunit RpsF. RimK is found in a wide range of bacteria with a conserved amino acid sequence, however, the genetic context and the role of this protein is highly diverse. By solving and comparing the structures of RimK homologs from two related but functionally divergent systems, we uncovered key structural differences that likely contribute to the different activity levels of each of these homologs. Moreover, we were able to clearly resolve the active site of this protein for the first time, resolving binding of the glutamate substrate. This work advances our understanding of how subtle differences in protein sequence and structure can have profound effects on protein activity, which can in turn result in widespread mechanistic changes

    Bacterial rotary export ATPases are allosterically regulated by the nucleotide second messenger cyclic-di-GMP

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    The widespread second messenger molecule cyclic di-GMP (cdG) regulates the transition from motile and virulent lifestyles to sessile, biofilm-forming ones in a wide range of bacteria. Many pathogenic and commensal bacterial-host interactions are known to be controlled by cdG signaling. Although the biochemistry of cyclic dinucleotide metabolism is well understood, much remains to be discovered about the downstream signaling pathways that induce bacterial responses upon cdG binding. As part of our ongoing research into the role of cdG signaling in plant-associated Pseudomonas species, we carried out an affinity capture screen for cdG binding proteins in the model organism Pseudomonas fluorescens SBW25. The flagella export AAA+ ATPase FliI was identified as a result of this screen and subsequently shown to bind specifically to the cdG molecule, with a KD in the low micromolar range. The interaction between FliI and cdG appears to be very widespread. In addition to FliI homologs from diverse bacterial species, high affinity binding was also observed for the type III secretion system homolog HrcN and the type VI ATPase ClpB2. The addition of cdG was shown to inhibit FliI and HrcN ATPase activity in vitro. Finally, a combination of site-specific mutagenesis, mass spectrometry, and in silico analysis was used to predict that cdG binds to FliI in a pocket of highly conserved residues at the interface between two FliI subunits. Our results suggest a novel, fundamental role for cdG in controlling the function of multiple important bacterial export pathways, through direct allosteric control of export ATPase proteins

    Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

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    Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

    A Comparison of Computed Tomography Measures for Diagnosing Cervical Spinal Stenosis Associated with Myelopathy: A Case-Control Study

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    Study DesignRetrospective comparative study.PurposeTo assess differences in computed tomography (CT) imaging parameters between patients with cervical myelopathy and controls.Overview of LiteratureThere is a lack of information regarding the best predictor of symptomatic stenosis based on osseous canal dimensions. We postulate that smaller osseous canal dimensions increase the risk of symptomatic central stenosis.MethodsCT images and medical records of patients with cervical myelopathy (19 patients, 8 males; average age, 64.4±13.4 years) and controls (18 patients, 14 males; average age, 60.4±11.0 years) were collected. A new measure called the laminar roof pitch angle (=angle between the lamina) was conducted along with linear measures, ratios and surrogates of canal perimeter and area at each level C2-C7 (222 levels). Receiver-operator curves were used to assess the diagnostic value of each. Rater reliability was assessed for the measures.ResultsThe medial-lateral (ML) diameter (at mid-pedicle level) and calculated canal area (=anterior-posterior.×ML diameters) were the most accurate and highly reliable. ML diameter below 23.5 mm and calculated canal area below 300 mm2 generated 82% to 84% sensitivity and 67% to 68% sensitivity. No significant correlations were identified between age, height, weight, body mass in dex and gender for each of the CT measures.ConclusionsCT measures including ML dimensions were most predictive. This study is the first to identify an important role for the ML dimension in cases of slowly progressive compressive myelopathy. A ML reserve may be protective when the canal is progressively compromised in the anterior-posterior dimension

    Efficacy of PermaNet® 2.0 and PermaNet® 3.0 against insecticide-resistant Anopheles gambiae in experimental huts in Côte d'Ivoire

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    <p>Abstract</p> <p>Background</p> <p>Pyrethroid resistance in vectors could limit the efficacy of long-lasting insecticidal nets (LLINs) because all LLINs are currently treated with pyrethroids. The goal of this study was to evaluate the efficacy and wash resistance of PermaNet<sup>® </sup>3.0 compared to PermaNet<sup>® </sup>2.0 in an area of high pyrethroid in Côte d'Ivoire. PermaNet<sup>® </sup>3.0 is impregnated with deltamethrin at 85 mg/m<sup>2 </sup>on the sides of the net and with deltamethrin and piperonyl butoxide on the roof. PermaNet<sup>® </sup>2.0 is impregnated with deltamethrin at 55 mg/m<sup>2 </sup>across the entire net.</p> <p>Methods</p> <p>The study was conducted in the station of Yaokoffikro, in central Côte d'Ivoire. The efficacy of intact unwashed and washed LLINs was compared over a 12-week period with a conventionally-treated net (CTN) washed to just before exhaustion. WHO cone bioassays were performed on sub-sections of the nets, using wild-resistant <it>An. gambiae </it>and Kisumu strains. Mosquitoes were collected five days per week and were identified to genus and species level and classified as dead or alive, then unfed or blood-fed.</p> <p>Results</p> <p>Mortality rates of over 80% from cone bioassays with wild-caught pyrethroid-resistant <it>An. gambiae </it>s.s were recorded only with unwashed PermaNet<sup>® </sup>3.0. Over 12 weeks, a total of 7,291 mosquitoes were collected. There were significantly more <it>An. gambiae </it>s.s. and <it>Culex </it>spp. caught in control huts than with other treatments (P < 0.001). The proportion of mosquitoes exiting the huts was significantly lower with the control than for the treatment arms (P < 0.001). Mortality rates with resistant <it>An. gambiae </it>s.s and <it>Culex </it>spp, were lower for the control than for other treatments (P < 0.001), which did not differ (P > 0.05) except for unwashed PermaNet<sup>® </sup>3.0 (P < 0.001), which gave significantly higher mortality (P < 0.001).</p> <p>Conclusions</p> <p>This study showed that unwashed PermaNet<sup>® </sup>3.0 caused significantly higher mortality against pyrethroid resistant <it>An. gambiae s.s </it>and <it>Culex </it>spp than PermaNet<sup>® </sup>2.0 and the CTN. The increased efficacy with unwashed PermaNet<sup>® </sup>3.0 over PermaNet<sup>® </sup>2.0 and the CTN was also demonstrated by higher KD and mortality rates (KD > 95% and mortality rate > 80%) in cone bioassays performed with wild pyrethroid-resistant <it>An. gambiae s.s </it>from Yaokoffikro.</p
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