Evaluating a transfer gradient assumption in a fomite-mediated microbial transmission model using an experimental and Bayesian approach

Current microbial exposure models assume that microbial exchange follows a concentration gradient during hand-to-surface contacts. Our objectives were to evaluate this assumption using transfer efficiency experiments and to evaluate a model's ability to explain concentration changes using approximate Bayesian computation (ABC) on these experimental data. Experiments were conducted with two phages (MS2, ΦX174) simultaneously to study bidirectional transfer. Concentrations on the fingertip and surface were quantified before and after fingertip-to-surface contacts. Prior distributions for surface and fingertip swabbing efficiencies and transfer efficiency were used to estimate concentrations on the fingertip and surface post contact. To inform posterior distributions, Euclidean distances were calculated for predicted detectable concentrations (log10 PFU cm−2) on the fingertip and surface post contact in comparison with experimental values. To demonstrate the usefulness of posterior distributions in calibrated model applications, posterior transfer efficiencies were used to estimate rotavirus infection risks for a fingertip-to-surface and subsequent fingertip-to-mouth contact. Experimental findings supported the transfer gradient assumption. Through ABC, the model explained concentration changes more consistently when concentrations on the fingertip and surface were similar. Future studies evaluating microbial transfer should consider accounting for differing fingertip-to-surface and surface-to-fingertip transfer efficiencies and extend this work for other microbial types

Improving drug discovery using a neural networks based parallel scoring function

Virtual Screening (VS) methods can considerably aid clinical research, predicting how ligands interact with drug targets. Most VS methods suppose a unique binding site for the target, but it has been demonstrated that diverse ligands interact with unrelated parts of the target and many VS methods do not take into account this relevant fact. This problem is circumvented by a novel VS methodology named BINDSURF that scans the whole protein surface to find new hotspots, where ligands might potentially interact with, and which is implemented in massively parallel Graphics Processing Units, allowing fast processing of large ligand databases. BINDSURF can thus be used in drug discovery, drug design, drug repurposing and therefore helps considerably in clinical research. However, the accuracy of most VS methods is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to solve this problem, we propose a novel approach where neural networks are trained with databases of known active (drugs) and inactive compounds, and later used to improve VS predictions.This work has been jointly supported by the Fundación Séneca (Agencia Regional de Ciencia y Tecnología de la Región de Murcia) under grant 15290/PI/2010, by the Spanish MINECO and the European Commission FEDER funds under grants TIN2009-14475-C04 and TIN2012-31345, and by the Catholic University of Murcia (UCAM) under grant PMAFI/26/12. This work was partially supported by the computing facilities of Extremadura Research Centre for Advanced Technologies (CETA-CIEMAT), funded by the European Regional Development Fund (ERDF). CETA-CIEMAT belongs to CIEMAT and the Government of Spain

Dynamical properties of liquid Al near melting. An orbital-free molecular dynamics study

The static and dynamic structure of liquid Al is studied using the orbital free ab-initio molecular dynamics method. Two thermodynamic states along the coexistence line are considered, namely T = 943 K and 1323 K for which X-ray and neutron scattering data are available. A new kinetic energy functional, which fulfills a number of physically relevant conditions is employed, along with a local first principles pseudopotential. In addition to a comparison with experiment, we also compare our ab-initio results with those obtained from conventional molecular dynamics simulations using effective interionic pair potentials derived from second order pseudopotential perturbation theory.Comment: 15 pages, 12 figures, 2 tables, submitted to PR

Multiple expressions of plume-ridge interaction in the Galapagos : volcanic lineaments and ridge jumps

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 13 (2012): Q05018, doi:10.1029/2012GC004093.Anomalous volcanism and tectonics between near-ridge mantle plumes and mid-ocean ridges provide important insights into the mechanics of plume-lithosphere interaction. We present new observations and analysis of multibeam, side scan sonar, sub-bottom chirp, and total magnetic field data collected during the R/V Melville FLAMINGO cruise (MV1007; May–June, 2010) to the Northern Galápagos Volcanic Province (NGVP), the region between the Galápagos Archipelago and the Galápagos Spreading Center (GSC) on the Nazca Plate, and to the region east of the Galápagos Transform Fault (GTF) on the Cocos Plate. The NGVP exhibits pervasive off-axis volcanism related to the nearby Galápagos hot spot, which has dominated the tectonic evolution of the region. Observations indicate that ~94% of the excess volcanism in our survey area occurs on the Nazca Plate in three volcanic lineaments. Identified faults in the NGVP are consistent with normal ridge spreading except for those within a ~60 km wide swath of transform-oblique faults centered on the GTF. These transform-oblique faults are sub-parallel to the elongation direction of larger lineament volcanoes, suggesting that lineament formation is influenced by the lithospheric stress field. We evaluate current models for lineament formation using existing and new observations as well as numerical models of mantle upwelling and melting. The data support a model where the lithospheric stress field controls the location of volcanism along the lineaments while several processes likely supply melt to these eruptions. Synthetic magnetic models and an inversion for crustal magnetization are used to determine the tectonic history of the study area. Results are consistent with creation of the GTF by two southward ridge jumps, part of a series of jumps that have maintained a plume-ridge separation distance of 145 km to 215 km since ~5 Ma.This work was supported by NSF grant OCE-0926637 and OCE-1030904 to DF and KH. DG’s work was supported by NSF grants EAR- 0838461 and EAR-1145271. Additional support was provided to E.M. by the Deep Ocean Exploration Institute at the Woods Hole Oceanographic Institution.2012-11-3

Compact \u3cb\u3e-300 kV\u3c/b\u3e dc Inverted Insulator Photogun With Biased Anode and Alkali-Antimonide Photocathode

This contribution describes the latest milestones of a multiyear program to build and operate a compact −300  kV dc high voltage photogun with inverted insulator geometry and alkali-antimonide photocathodes. Photocathode thermal emittance measurements and quantum efficiency charge lifetime measurements at average current up to 4.5 mA are presented, as well as an innovative implementation of ion generation and tracking simulations to explain the benefits of a biased anode to repel beam line ions from the anode-cathode gap, to dramatically improve the operating lifetime of the photogun and eliminate the occurrence of micro-arc discharges

DNA Methylation Causes Predominant Maternal Controls of Plant Embryo Growth

The parental conflict hypothesis predicts that the mother inhibits embryo growth counteracting growth enhancement by the father. In plants the DNA methyltransferase MET1 is a central regulator of parentally imprinted genes that affect seed growth. However the relation between the role of MET1 in imprinting and its control of seed size has remained unclear. Here we combine cytological, genetic and statistical analyses to study the effect of MET1 on seed growth. We show that the loss of MET1 during male gametogenesis causes a reduction of seed size, presumably linked to silencing of the paternal allele of growth enhancers in the endosperm, which nurtures the embryo. However, we find no evidence for a similar role of MET1 during female gametogenesis. Rather, the reduction of MET1 dosage in the maternal somatic tissues causes seed size increase. MET1 inhibits seed growth by restricting cell division and elongation in the maternal integuments that surround the seed. Our data demonstrate new controls of seed growth linked to the mode of reproduction typical of flowering plants. We conclude that the regulation of embryo growth by MET1 results from a combination of predominant maternal controls, and that DNA methylation maintained by MET1 does not orchestrate a parental conflict

Geochemistry of lavas from the 2005–2006 eruption at the East Pacific Rise, 9°46′N–9°56′N : implications for ridge crest plumbing and decadal changes in magma chamber compositions

Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 11 (2010): Q05T09, doi:10.1029/2009GC002977.Detailed mapping, sampling, and geochemical analyses of lava flows erupted from an ∼18 km long section of the northern East Pacific Rise (EPR) from 9°46′N to 9°56′N during 2005–2006 provide unique data pertaining to the short-term thermochemical changes in a mid-ocean ridge magmatic system. The 2005–2006 lavas are typical normal mid-oceanic ridge basalt with strongly depleted incompatible trace element patterns with marked negative Sr and Eu/Eu* anomalies and are slightly more evolved than lavas erupted in 1991–1992 at the same location on the EPR. Spatial geochemical differences show that lavas from the northern and southern limits of the 2005–2006 eruption are more evolved than those erupted in the central portion of the fissure system. Similar spatial patterns observed in 1991–1992 lavas suggest geochemical gradients are preserved over decadal time scales. Products of northern axial and off-axis fissure eruptions are consistent with the eruption of cooler, more fractionated lavas that also record a parental melt component not observed in the main suite of 2005–2006 lavas. Radiogenic isotopic ratios for 2005–2006 lavas fall within larger isotopic fields defined for young axial lavas from 9°N to 10°N EPR, including those from the 1991–1992 eruption. Geochemical data from the 2005–2006 eruption are consistent with an invariable mantle source over the spatial extent of the eruption and petrogenetic processes (e.g., fractional crystallization and magma mixing) operating within the crystal mush zone and axial magma chamber (AMC) before and during the 13 year repose period. Geochemical modeling suggests that the 2005–2006 lavas represent differentiated residual liquids from the 1991–1992 eruption that were modified by melts added from deeper within the crust and that the eruption was not initiated by the injection of hotter, more primitive basalt directly into the AMC. Rather, the eruption was driven by AMC pressurization from persistent or episodic addition of more evolved magma from the crystal mush zone into the overlying subridge AMC during the period between the two eruptions. Heat balance calculations of a hydrothermally cooled AMC support this model and show that continual addition of melt from the mush zone was required to maintain a sizable AMC over this time interval.This work has been supported by NSF grants OCE‐0525863 and OCE‐0732366 (D. J. Fornari and S. A. Soule), OCE‐0636469 (K. H. Rubin), and OCE‐ 0138088 (M. R. Perfit), as well as postdoctoral fellowship funds from the University of Florida

Automated Discrimination of Brain Pathological State Attending to Complex Structural Brain Network Properties: The Shiverer Mutant Mouse Case

Neuroimaging classification procedures between normal and pathological subjects are sparse and highly dependent of an expert's clinical criterion. Here, we aimed to investigate whether possible brain structural network differences in the shiverer mouse mutant, a relevant animal model of myelin related diseases, can reflect intrinsic individual brain properties that allow the automatic discrimination between the shiverer and normal subjects. Common structural networks properties between shiverer (C3Fe.SWV Mbpshi/Mbpshi, n = 6) and background control (C3HeB.FeJ, n = 6) mice are estimated and compared by means of three diffusion weighted MRI (DW-MRI) fiber tractography algorithms and a graph framework. Firstly, we found that brain networks of control group are significantly more clustered, modularized, efficient and optimized than those of the shiverer group, which presented significantly increased characteristic path length. These results are in line with previous structural/functional complex brain networks analysis that have revealed topologic differences and brain network randomization associated to specific states of human brain pathology. In addition, by means of network measures spatial representations and discrimination analysis, we show that it is possible to classify with high accuracy to which group each subject belongs, providing also a probability value of being a normal or shiverer subject as an individual anatomical classifier. The obtained correct predictions (e.g., around 91.6–100%) and clear spatial subdivisions between control and shiverer mice, suggest that there might exist specific network subspaces corresponding to specific brain disorders, supporting also the point of view that complex brain network analyses constitutes promising tools in the future creation of interpretable imaging biomarkers

A large topographic feature on the surface of the trans-Neptunian object (307261) 2002 MS4_4 measured from stellar occultations

This work aims at constraining the size, shape, and geometric albedo of the dwarf planet candidate 2002 MS4 through the analysis of nine stellar occultation events. Using multichord detection, we also studied the object's topography by analyzing the obtained limb and the residuals between observed chords and the best-fitted ellipse. We predicted and organized the observational campaigns of nine stellar occultations by 2002 MS4 between 2019 and 2022, resulting in two single-chord events, four double-chord detections, and three events with three to up to sixty-one positive chords. Using 13 selected chords from the 8 August 2020 event, we determined the global elliptical limb of 2002 MS4. The best-fitted ellipse, combined with the object's rotational information from the literature, constrains the object's size, shape, and albedo. Additionally, we developed a new method to characterize topography features on the object's limb. The global limb has a semi-major axis of 412 $\pm$ 10 km, a semi-minor axis of 385 $\pm$ 17 km, and the position angle of the minor axis is 121 $^\circ$ $\pm$ 16$^\circ$. From this instantaneous limb, we obtained 2002 MS4's geometric albedo and the projected area-equivalent diameter. Significant deviations from the fitted ellipse in the northernmost limb are detected from multiple sites highlighting three distinct topographic features: one 11 km depth depression followed by a 25$^{+4}_{-5}$ km height elevation next to a crater-like depression with an extension of 322 $\pm$ 39 km and 45.1 $\pm$ 1.5 km deep. Our results present an object that is $\approx$138 km smaller in diameter than derived from thermal data, possibly indicating the presence of a so-far unknown satellite. However, within the error bars, the geometric albedo in the V-band agrees with the results published in the literature, even with the radiometric-derived albedo

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised