A comprehensive approach to simulation of cartridge filtration using CFD

Household water treatment (HWT) systems are widely used for the provision of potable water in many countries with their low-cost key to attaining universal and equitable access to safe and affordable drinking water, Sustainable Development Goal 6.1. Removal of suspended particles (turbidity) from water sources via cartridge filters is often the first step of a HWT system, with the primary treatment increasing the efficiency of a subsequent disinfection step. Whilst the performance of cartridge filters (removal efficiency and pressure drop) can be determined experimentally in long experiments with high volumes of water, numerical simulation adds fundamental insight to the influence of fluid dynamics on particle deposition and vice versa. In this study, a novel computational fluid dynamic (CFD) model was developed to simulate the fundamental mechanisms underpinning the removal of particles within the widely used 10 in. cartridge filter, informed by and complemented with laboratory validation. The Eulerian approach was used to simulate fluid flow with the Lagrangian approach adopted for particle tracking. Rosin-Rammler distribution was implemented with respect to the particle size distribution of the diatomaceous earth particles used in the experiments. Given particles were non-spherical (disk shape), Wadell's sphericity was included to account for the effect of particle shape on drag force. A porous domain was implemented to simulate the filter element through addition of a source term to the momentum equations, with the likelihood of particle deposition, detachment and rebound also considered. Laboratory based validation studies confirmed the novel CFD model to accurately model removal of turbidity and predict the pressure drop across the filter with Root Mean Square Percentage Error (RMSPE) of less than 3%. The simulated location of particle deposition on the filter elements closely matched images taken at several stages during filtration experiments with the model aiding understanding of pattern of particle removal along and within the porous filter structure. This novel and comprehensive modelling methodology can be utilized to simulate the filtration process at the macro-scale, permitting evaluation of new filter designs and materials for advanced filtration systems; ultimately improving HWT system performance and reducing costs to users.</p

A T-type channel-calmodulin complex triggers αCaMKII activation

Abstract Calmodulin (CaM) is an important signaling molecule that regulates a vast array of cellular functions by activating second messengers involved in cell function and plasticity. Low voltage-activated calcium channels of the Cav3 family have the important role of mediating low threshold calcium influx, but were not believed to interact with CaM. We find a constitutive association between CaM and the Cav3.1 channel at rest that is lost through an activity-dependent and Cav3.1 calcium-dependent CaM dissociation. Moreover, Cav3 calcium influx is sufficient to activate αCaMKII in the cytoplasm in a manner that depends on an intact Cav3.1 C-terminus needed to support the CaM interaction. Our findings thus establish that T-type channel calcium influx invokes a novel dynamic interaction between CaM and Cav3.1 channels to trigger a signaling cascade that leads to αCaMKII activation

Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells.

The generation of effective and safe nanoagents for biological applications requires their physicochemical characteristics to be tunable, and their cellular interactions to be well characterized. Here, the controlled synthesis is developed for preparing high-aspect ratio gold nanotubes (AuNTs) with tailorable wall thickness, microstructure, composition, and optical characteristics. The modulation of optical properties generates AuNTs with strong near infrared absorption. Surface modification enhances dispersibility of AuNTs in aqueous media and results in low cytotoxicity. The uptake and trafficking of these AuNTs by primary mesothelioma cells demonstrate their accumulation in a perinuclear distribution where they are confined initially in membrane-bound vesicles from which they ultimately escape to the cytosol. This represents the first study of the cellular interactions of high-aspect ratio 1D metal nanomaterials and will facilitate the rational design of plasmonic nanoconstructs as cytosolic nanoagents for potential diagnosis and therapeutic applications.BLF-Papworth Fellowship from the British Lung Foundation and the Victor Dahdaleh Foundation

Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo

© 2020 The Author(s) Implantation of medical devices can result in inflammation. A large library of polymers is screened, and a selection found to promote macrophage differentiation towards pro- or anti-inflammatory phenotypes. The bioinstructive properties of these materials are validated within a rodent model. By identifying novel materials with immune-instructive properties, the relationship between material-immune cell interactions could be investigated, and this offers exciting possibilities to design novel bioinstructive materials that can be used for numerous clinical applications including medical implants

A tetrapeptide class of biased analgesics from an Australian fungus targets the μ-opioid receptor

An Australian estuarine isolate ofPenicilliumsp. MST-MF667 yielded3 tetrapeptides named the bilaids with an unusual alternating LDLDchirality. Given their resemblance to known short peptide opioidagonists, we elucidated that they were weak (Kilow micromolar)μ-opioid agonists, which led to the design of bilorphin, a potent andselectiveμ-opioid receptor (MOPr) agonist (Ki1.1 nM). In sharp con-trast to all-natural product opioid peptides that efficaciously recruitβ-arrestin, bilorphin is G protein biased, weakly phosphorylatingthe MOPr and marginally recruitingβ-arrestin, with no receptorinternalization. Importantly, bilorphin exhibits a similar G proteinbias to oliceridine, a small nonpeptide with improved overdosesafety. Molecular dynamics simulations of bilorphin and thestrongly arrestin-biased endomorphin-2 with the MOPr indicatedistinct receptor interactions and receptor conformations thatcould underlie their large differences in bias. Whereas bilorphinis systemically inactive, a glycosylated analog, bilactorphin, isorally active with similar in vivo potency to morphine. Bilorphinis both a unique molecular tool that enhances understanding ofMOPr biased signaling and a promising lead in the development ofnext generation analgesics

Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components

Siesta: Recent developments and applications

A review of the present status, recent enhancements, and applicability of the SIESTA program is presented. Since its debut in the mid-1990s, SIESTA’s flexibility, efficiency, and free distribution have given advanced materials simulation capabilities to many groups worldwide. The core methodological scheme of SIESTA combines finite-support pseudo-atomic orbitals as basis sets, norm-conserving pseudopotentials, and a realspace grid for the representation of charge density and potentials and the computation of their associated matrix elements. Here, we describe the more recent implementations on top of that core scheme, which include full spin–orbit interaction, non-repeated and multiple-contact ballistic electron transport, density functional theory (DFT)+U and hybrid functionals, time-dependent DFT, novel reduced-scaling solvers, density-functional perturbation theory, efficient van der Waals non-local density functionals, and enhanced molecular-dynamics options. In addition, a substantial effort has been made in enhancing interoperability and interfacing with other codes and utilities, such as WANNIER90 and the second-principles modeling it can be used for, an AiiDA plugin for workflow automatization, interface to Lua for steering SIESTA runs, and various post-processing utilities. SIESTA has also been engaged in the Electronic Structure Library effort from its inception, which has allowed the sharing of various low-level libraries, as well as data standards and support for them, particularly the PSeudopotential Markup Language definition and library for transferable pseudopotentials, and the interface to the ELectronic Structure Infrastructure library of solvers. Code sharing is made easier by the new open-source licensing model of the program. This review also presents examples of application of the capabilities of the code, as well as a view of on-going and future developments. Published under license by AIP Publishing.Siesta development was historically supported by different Spanish National Plan projects (Project Nos. MEC-DGES-PB95-0202, MCyT-BFM2000-1312, MEC-BFM2003-03372, FIS2006-12117, FIS2009-12721, FIS2012-37549, FIS2015-64886-P, and RTC-2016-5681-7), the latter one together with Simune Atomistics Ltd. We are thankful for financial support from the Spanish Ministry of Science, Innovation and Universities through Grant No. PGC2018-096955-B. We acknowledge the Severo Ochoa Center of Excellence Program [Grant Nos. SEV-2015-0496 (ICMAB) and SEV-2017-0706 (ICN2)], the GenCat (Grant No. 2017SGR1506), and the European Union MaX Center of Excellence (EU-H2020 Grant No. 824143). P.G.-F. acknowledges support from Ramón y Cajal (Grant No. RyC-2013-12515). J.I.C. acknowledges Grant No. RTI2018-097895-B-C41. R.C. acknowledges the European Union’s Horizon 2020 Research and Innovation Program under Marie Skłodoswka-Curie Grant Agreement No. 665919. D.S.P, P.K., and P.B. acknowledge Grant No. MAT2016-78293-C6, FET-Open No. 863098, and UPV-EHU Grant No. IT1246-19. V. W. Yu was supported by a MolSSI Fellowship (U.S. NSF Award No. 1547580), and V.B. and V.W.Y. were supported by the ELSI Development by the NSF (Award No. 1450280). We also acknowledge Honghui Shang and Xinming Qin for giving us access to the honpas code, where a preliminary version of the hybrid functional support described here was implemented. We are indebted to other contributors to the Siesta project whose names can be seen in the Docs/Contributors.txt file of the Siesta distribution, and we thank those, too many to list, contributing fixes, comments, clarifications, and documentation for the code.Peer reviewe

Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability

In the present study we report on the use of speed congenics to generate a C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which uniquely exhibits minimal intergenerational instability. We also report the first identification of the R6/2 transgene insertion site. The relatively stable line of 110 CAG R6/2 mice was characterized for the onset of behavioral impairments in motor, cognitive and psychiatric-related phenotypes as well as the progression of disease-related impairments from 4 to 10 weeks of age. 110Q mice exhibited many of the phenotypes commonly associated with the R6/2 model including reduced activity and impairments in rotarod performance. The onset of many of the phenotypes occurred around 6 weeks and was progressive across age. In addition, some phenotypes were observed in mice as early as 4 weeks of age. The present study also reports the onset and progression of changes in several molecular phenotypes in the novel R6/2 mice and the association of these changes with behavioral symptom onset and progression. Data from TR-FRET suggest an association of mutant protein state changes (soluble versus aggregated) in disease onset and progression