The anisotropy of granular materials

The effect of the anisotropy on the elastoplastic response of two dimensional packed samples of polygons is investigated here, using molecular dynamics simulation. We show a correlation between fabric coefficients, characterizing the anisotropy of the granular skeleton, and the anisotropy of the elastic response. We also study the anisotropy induced by shearing on the subnetwork of the sliding contacts. This anisotropy provides an explanation to some features of the plastic deformation of granular media.Comment: Submitted to PR

The impact of a change on the size of the smoke compartment in the evacuation of health care facilities

Evacuation in health-care facilities is complex due to the physical impairment of the patients. This kind of evacuation usually requires the assistance of the workforce members. A proposed change of NFPA 101, Life Safety Code, would increase the maximum allowable size of a smoke compartment (a space within the building enclosed by smoke barriers on all sides that restricts the movement of smoke) in health-care occupancies from 2090 m2 to 3700 m2, almost double the size. This study aims to analyse the impact of this change in the required time for evacuating patients during a fire in order to understand the consequences of that potential change. This paper is focused on the area where the patient?s rooms are located. The evacuation scenario is a floor plan comprised of four smoke compartments. To analyse the proposed change, the smoke barriers between two adjacent compartments were removed in a floor plan and three ratios of number of patients per one staff member were considered (4:1, 3:1 and 2:1). A computational methodology was conducted to calibrate the model STEPS for simulating assisted evacuation processes. In addition, Fire Dynamic Simulator (FDS) was used to simulate the fire and smoke spread in a table and a PC to compare fire and evacuation results The evacuation results show that the change of the smoke compartment size increases the mean evacuation time by 23%; however, the fire results show that the available safe egress time is 16 min for both smaller and large smoke compartment. The ratio of the number of patients per staff member is also a strong factor that increases the evacuation up to 82% when comparing the ratios of 2 patients per staff member and 4 patients per staff member

Developing a tool for mapping adult mental health care provision in Europe: the REMAST research protocol and its contribution to better integrated care

Introduction: Mental health care is a critical area to better understand integrated care and to pilot the different components of the integrated care model. However, there is an urgent need for better tools to compare and understand the context of integrated mental health care in Europe. Method: The REMAST tool (REFINEMENT MApping Services Tool) combines a series of standardised health service research instruments and geographical information systems (GIS) to develop local atlases of mental health care from the perspective of horizontal and vertical integrated care. It contains five main sections: (a) Population Data; (b) the Verona Socio-economic Status (SES) Index; (c) the Mental Health System Checklist; (d) the Mental Health Services Inventory using the DESDE-LTC instrument; and (e) Geographical Data. Expected results: The REMAST tool facilitates context analysis in mental health by providing the comparative rates of mental health service provision according to the availability of main types of care; care placement capacity; workforce capacity; and geographical accessibility to services in the local areas in eight study areas in Austria, England, Finland, France, Italy, Norway, Romania and Spain. Discussion: The outcomes of this project will facilitate cooperative work and knowledge transfer on mental health care to the different agencies involved in mental health planning and provision. This project would improve the information to users and society on the available resources for mental health care and system thinking at the local level by the different stakeholders. The techniques used in this project and the knowledge generated could eventually be transferred to the mapping of other fields of integrated care

The Experiment Data Depot: A Web-Based Software Tool for Biological Experimental Data Storage, Sharing, and Visualization

Although recent advances in synthetic biology allow us to produce biological designs more efficiently than ever, our ability to predict the end result of these designs is still nascent. Predictive models require large amounts of high-quality data to be parametrized and tested, which are not generally available. Here, we present the Experiment Data Depot (EDD), an online tool designed as a repository of experimental data and metadata. EDD provides a convenient way to upload a variety of data types, visualize these data, and export them in a standardized fashion for use with predictive algorithms. In this paper, we describe EDD and showcase its utility for three different use cases: storage of characterized synthetic biology parts, leveraging proteomics data to improve biofuel yield, and the use of extracellular metabolite concentrations to predict intracellular metabolic fluxes

Derivation and external validation of the SIMPLICITY score as a simple immune-based risk score to predict infection in kidney transplant recipients

Existing approaches for infection risk stratification in kidney transplant recipients are suboptimal. Here, we aimed to develop and validate a weighted score integrating non-pathogen-specific immune parameters and clinical variables to predict the occurrence of post-transplant infectious complications. To this end, we retrospectively analyzed a single-center derivation cohort of 410 patients undergoing kidney transplantation in 2008-2013 in Madrid. Peripheral blood lymphocyte subpopulations, serum immunoglobulin and complement levels were measured at one-month post-transplant. The primary and secondary outcomes were overall and bacterial infection through month six. A point score was derived from a logistic regression model and prospectively applied on a validation cohort of 522 patients undergoing kidney transplantation at 16 centers throughout Spain in 2014-2015. The SIMPLICITY score consisted of the following variables measured at month one after transplantation: C3 level, CD4+ T-cell count, CD8+ T-cell count, IgG level, glomerular filtration rate, recipient age, and infection within the first month. The discrimination capacity in the derivation and validation cohorts was good for overall (areas under the receiver operating curve of 0.774 and 0.730) and bacterial infection (0.767 and 0.734, respectively). The cumulative incidence of overall infection significantly increased across risk categories in the derivation (low-risk 13.7%; intermediate-risk, 35.9%; high-risk 77.6%) and validation datasets (10.2%, 28.9% and 50.4%, respectively). Thus, the SIMPLICITY score, based on easily available immune parameters, allows for stratification of kidney transplant recipients at month one according to their expected risk of subsequent infection

LYACOLORE: synthetic datasets for current and future Lyman-alpha forest BAO surveys

The statistical power of Lyman-α forest Baryon Acoustic Oscillation (BAO) measurements is set to increase significantly in the coming years as new instruments such as the Dark Energy Spectroscopic Instrument deliver progressively more constraining data. Generating mock datasets for such measurements will be important for validating analysis pipelines and evaluating the effects of systematics. With such studies in mind, we present LyaCoLoRe: a package for producing synthetic Lyman-α forest survey datasets for BAO analyses. LyaCoLoRe transforms initial Gaussian random field skewers into skewers of transmitted flux fraction via a number of fast approximations. In this work we explain the methods of producing mock datasets used in LyaCoLoRe, and then measure correlation functions on a suite of realisations of such data. We demonstrate that we are able to recover the correct BAO signal, as well as large-scale bias parameters similar to literature values. Finally, we briefly describe methods to add further astrophysical effects to our skewers—high column density systems and metal absorbers—which act as potential complications for BAO analyses

Toward industrial production of isoprenoids in Escherichia coli: Lessons learned from CRISPR-Cas9 based optimization of a chromosomally integrated mevalonate pathway

Escherichia coli has been the organism of choice for the production of different chemicals by engineering native and heterologous pathways. In the present study, we simultaneously address some of the main issues associated with E. coli as an industrial platform for isoprenoids, including an inability to grow on sucrose, a lack of endogenous control over toxic mevalonate (MVA) pathway intermediates, and the limited pathway engineering into the chromosome. As a proof of concept, we generated an E. coli DH1 strain able to produce the isoprenoid bisabolene from sucrose by integrating the cscAKB operon into the chromosome and by expressing a heterologous MVA pathway under stress-responsive control. Production levels dropped dramatically relative to plasmid-mediated expression when the entire pathway was integrated into the chromosome. In order to optimize the chromosomally integrated MVA pathway, we established a CRISPR-Cas9 system to rapidly and systematically replace promoter sequences. This strategy led to higher pathway expression and a fivefold improvement in bisabolene production. More interestingly, we analyzed proteomics data sets to understand and address some of the challenges associated with metabolic engineering of the chromosomally integrated pathway. This report shows that integrating plasmid-optimized operons into the genome and making them work optimally is not a straightforward task and any poor engineering choices on the chromosome may lead to cell death rather than just resulting in low titers. Based on these results, we also propose directions for chromosomal metabolic engineering

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli

Monoterpenes (C10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP production but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes. Biotechnol. Bioeng. 2017;114: 1703-1712. © 2017 Wiley Periodicals, Inc