Molecular basis for substrate recognition and septum cleavage by AtlA, the major N-acetylglucosaminidase of Enterococcus faecalis

The cleavage of septal peptidoglycan at the end of cell division facilitates the separation of the two daughter cells. The hydrolases involved in this process (called autolysins) are potentially lethal enzymes that can cause cell death; their activity, therefore, must be tightly controlled during cell growth. In Enterococcus faecalis, the N-acetylglucosaminidase AtlA plays a predominant role in cell separation. atlA mutants form long cell chains and are significantly less virulent in the zebrafish model of infection. The attenuated virulence of atlA mutants is underpinned by a limited dissemination of bacterial chains in the host organism and a more efficient uptake by phagocytes that clear the infection. AtlA has structural homologs in other important pathogens, such as Listeria monocytogenes and Salmonella typhimurium, and therefore represents an attractive model to design new inhibitors of bacterial pathogenesis. Here, we provide a 1.6 Å crystal structure of the E. faecalis AtlA catalytic domain that reveals a closed conformation of a conserved β-hairpin and a complex network of hydrogen bonds that bring two catalytic residues to the ideal distance for an inverting mechanism. Based on the model of the AtlA-substrate complex, we identify key residues critical for substrate recognition and septum cleavage during bacterial growth. We propose that this work will provide useful information for the rational design of specific inhibitors targeting this enterococcal virulence factor and its orthologs in other pathogens

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Searches for electroweak neutralino and chargino production in channels with Higgs, Z, and W bosons in pp collisions at 8 TeV

Searches for supersymmetry (SUSY) are presented based on the electroweak pair production of neutralinos and charginos, leading to decay channels with Higgs, Z, and W bosons and undetected lightest SUSY particles (LSPs). The data sample corresponds to an integrated luminosity of about 19.5 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV collected in 2012 with the CMS detector at the LHC. The main emphasis is neutralino pair production in which each neutralino decays either to a Higgs boson (h) and an LSP or to a Z boson and an LSP, leading to hh, hZ, and ZZ states with missing transverse energy (E-T(miss)). A second aspect is chargino-neutralino pair production, leading to hW states with E-T(miss). The decays of a Higgs boson to a bottom-quark pair, to a photon pair, and to final states with leptons are considered in conjunction with hadronic and leptonic decay modes of the Z and W bosons. No evidence is found for supersymmetric particles, and 95% confidence level upper limits are evaluated for the respective pair production cross sections and for neutralino and chargino mass values

Description of Hemicycliophora cardamomi sp. n. (Nematoda : Hemicycliophoridae) associated with Amomum longiligulare T.L. Wu and a web-based key for the identification of Hemicycliophora spp.

During a survey of plant diseases in the Central Highlands of Vietnam, a new plant-parasitic nematode, Hemicycliophora cardamomi sp. n., was discovered in the growing areas of Amomum longiligulare, a valuable medicinal plant with high economical value. The new species is characterized by a cuticular sheath loosely fitting body; a labial region continuous to the body contour bearing 3 annuli; a lateral field frequently marked by a discontinuous single line with indistinct additional short lines in some parts along the body; a modified vulval lip with an anterior lip c. 4 annuli long; and a post-vulval body tapering to a pointed tail tip with an abrupt constriction at the last third of the post-vulval body. Morphology and molecular characterizations of D2-D3 expansion segment of 28S rRNA, ITS, and COI mtDNA gene regions clearly distinguish the new species from all other 133 known species. This study also provides a newly developed web-based key for the identification of Hemicycliophora spp. in order to accelerate the identification process, to minimize the increasing error load associated with larger datasets, and to avoid any dependence on a single starting entry. This key includes both an existing Bray-Curtis similarity measure and a newly developed similarity formula

Impedance control of a hydraulically actuated robotic excavator

In robotic excavation, hybrid position/force control has been proposed for bucket digging trajectory following. In hybrid position/force control, the control mode is required to switch between position- and force-control depending on whether the bucket is in free space or in contact with the soil during the process. Alternatively, impedance control can be applied such that one control mode is employed in both free and constrained motion. This paper presents a robust sliding controller that implements impedance control for a backhoe excavator. The control law consists of three components: an equivalent control, a switching control and a tuning control. Given an excavation task in world space, inverse kinematic and dynamic models are used to convert the task into a desired digging trajectory in joint space. The proposed controller is applied to provide good tracking performance with attenuated vibration at bucket-soil contact points. From the control signals and the joint angles of the excavator, the piston position and ram force of each hydraulic cylinder for the axis control of the boom, arm, and bucket can be determined. The problem is then how to find the control voltage applied to each servovalve to achieve force and position tracking of each electrohydraulic system for the axis motion of the boom, arm, and bucket. With an observer-based compensation for disturbance force including hydraulic friction, tracking of the piston ram force and position is guaranteed using robust sliding control. High performance and strong robustness can be obtained as demonstrated by simulation and experiments performed on a hydraulically actuated robotic excavator. The results obtained suggest that the proposed control technique can provide robust performance when employed in autonomous excavation with soil contact considerations.

Injection strategies to overcome gravity segregation in simultaneous gas and water injection into homogeneous reservoirs

We extend a model for gravity segregation in steady-state gas/water injection into homogeneous reservoirs for enhanced oil recovery (EOR). A new equation relates the distance gas and water flow together directly to injection pressure, independent of fluid mobilities or injection rate. We consider three additional cases: coinjection of gas and water over only a portion of the formation interval, injection of water above gas over the entire formation interval, and injection of water and gas in separate zones well separated from each other. If gas and water are injected at fixed total volumetric rates, the horizontal distance to the point of complete segregation is the same, whether gas and water are coinjected over all or any portion of the formation interval. At fixed injection pressure, the deepest penetration of mixed gas and water flow is expected when fluids are injected along the entire formation interval. At fixed total injection rate, injection of water above gas gives deeper penetration before complete segregation than does coinjection, but again exactly where the two fluids are injected does not affect the distance to the point of segregation. At fixed injection pressure, injection of water above gas is predicted to give deeper penetration before complete segregation. When injection pressure is limited, the best strategy for simultaneous injection of both phases from a vertical well would be to inject gas at the bottom of the reservoir and water over the rest of the reservoir height, with the ratio of the injection intervals adjusted to maximize overall injectivity. The 2D model applies equally to gas/water flow and to foam, and to injection of water above gas from separate intervals of a vertical well or from two parallel horizontal wells, as long as injection is uniform along each horizontal well. Sample computer simulations for foam injection agree well with the model predictions if numerical dispersion is controlled

Injection strategies to overcome gravity segregation in simultaneous gas and water injection into homogeneous reservoirs

We extend a model for gravity segregation in steady-state gas/water injection into homogeneous reservoirs for enhanced oil recovery (EOR). A new equation relates the distance gas and water flow together directly to injection pressure, independent of fluid mobilities or injection rate. We consider three additional cases: coinjection of gas and water over only a portion of the formation interval, injection of water above gas over the entire formation interval, and injection of water and gas in separate zones well separated from each other. If gas and water are injected at fixed total volumetric rates, the horizontal distance to the point of complete segregation is the same, whether gas and water are coinjected over all or any portion of the formation interval. At fixed injection pressure, the deepest penetration of mixed gas and water flow is expected when fluids are injected along the entire formation interval. At fixed total injection rate, injection of water above gas gives deeper penetration before complete segregation than does coinjection, but again exactly where the two fluids are injected does not affect the distance to the point of segregation. At fixed injection pressure, injection of water above gas is predicted to give deeper penetration before complete segregation. When injection pressure is limited, the best strategy for simultaneous injection of both phases from a vertical well would be to inject gas at the bottom of the reservoir and water over the rest of the reservoir height, with the ratio of the injection intervals adjusted to maximize overall injectivity. The 2D model applies equally to gas/water flow and to foam, and to injection of water above gas from separate intervals of a vertical well or from two parallel horizontal wells, as long as injection is uniform along each horizontal well. Sample computer simulations for foam injection agree well with the model predictions if numerical dispersion is controlled

Comparative analysis of phenolic content and in vitro bioactivities of Bidens pilosa L. flowers and leaves as affected by extraction solvents

Bidens pilosa L., native to South America, is valued for its purposes as a food and medicine. The study aimed to examine phenolics, antioxidant activity and inhibitory effects of B. pilosa flower and leaf extracts on albumin denaturation, α-glucosidase, α-amylase, xanthine oxidase, and tyrosinase. The choice of extractants (water, methanol, acetone, and ethyl acetate) greatly influenced the phenolic content and bioactivities of the extracts. The results demonstrated the flower and leaf extracts differed significantly with respect to total phenolic content and abilities to inhibit albumin denaturation, α-amylase, and xanthine oxidase. The ethyl acetate extracts may show the strongest activity to scavenge DPPH radicals, to inhibit α-amylase and α-glucosidase, and to protect albumin against denaturation. The aqueous extract possessed the strongest capacity to inhibit xanthine oxidase while the acetonic extract was more effective in suppressing tyrosinase compared to the others