Dissipative particle dynamics simulation of critical pore size in a lipid bilayer membrane

C.B. was partially supported by the NSF through grant no. DMS-1148284. M.C. gratefully acknowledges support of EPSRC grant no. EP/N014642/1 (EPSRC Centre for Multiscale Soft Tissue Mechanics–With Application to Heart & Cancer). A.M. was partially supported by the NSF through grant nos. DMS-1521266 and DMS-1552903.We investigate with computer simulations the critical radius of pores in a lipid bilayer membrane. Ilton et al. (Ilton et al. 2016 Phys. Rev. Lett.117, 257801 (doi:10.1103/PhysRevLett.117.257801)) recently showed that nucleated pores in a homopolymer film can increase or decrease in size, depending on whether they are larger or smaller than a critical size which scales linearly with film thickness. Using dissipative particle dynamics, a particle-based simulation method, we investigate the same scenario for a lipid bilayer membrane whose structure is determined by lipid–water interactions. We simulate a perforated membrane in which holes larger than a critical radius grow, while holes smaller than the critical radius close, as in the experiment of Ilton et al. (Ilton et al. 2016 Phys. Rev. Lett.117, 257801 (doi:10.1103/PhysRevLett.117.257801)). By altering key system parameters such as the number of particles per lipid and the periodicity, we also describe scenarios in which pores of any initial size can seal or even remain stable, showing a fundamental difference in the behaviour of lipid membranes from polymer films.Publisher PDFPeer reviewe

Solid-State Proton Nuclear Magnetic Resonance Studies of Hydrogen Site Occupancies, Electronic Structure Properties, and Diffusion Behavior in Transition Metal Hydrides

Solid-state NMR techniques have been used to measure the proton lineshapes, Knight shifts, and relaxation times in several transition metal hydrides. The objective of these studies is to obtain a better understanding of the roles of host metal structure and substitutional alloying on the hydrogen site occupancy, the electronic structure properties, and diffusion mechanisms. An improved method for observing the rigid-lattice proton lineshapes and extracting the second moments has been developed. Comparisons of the experimental second moments for polycrystalline samples with the values calculated from Van Vleck formulas for nuclear dipolar interactions have indicated that only tetrahedral interstitial sites are occupied by the protons in TiHx, ZrHx, crystalline TiCuH0.94, Ti2CuH1.9, and Zr2PdHx (with x &lt; 2) while both tetrahedral and octahedral sites can be occupied in amorphous a-TiCuH1.4, Ti2CuH2.6, and Zr2PdHx (x &gt; 2). The proton Knight shifts and low-temperature spin-lattice relaxation times have been related to the local densities of electron states at the Fermi levels N(EF) in Ti1-yVyHx, TiCr1.8Hx, TiCr1.9Hx, TiCuHx, Ti2CuHx, ZrHx, and Zr2PdHx. The dominant conduction electron hyperfine interaction for protons is a transferred "core-polarization" of the paired hydrogen 1s electrons through spin exchange with the unpaired metal d electrons. The proton NMR parameters have confirmed that decreases in N(EF) through a Jahn-Teller type mechanism are associated with the temperature and composition dependent tetragonal distortions in Ti1-yVyH1.95 and ZrHx (where 1.75 ≤ x ≤ 2.0). The proton NMR results are consistent with recent band theory calculations and photoemission spectra. Unusual N(EF) increases with hydrogen content, which are supported by independent magnetic susceptibility data, have been observed in TiCr1.8Hx, TiCr1.9Hx, and Ti2CuHx. The proton parameters suggest that significant differences in N(EF) for the crystalline and amorphous phases of TiCuHx and Zr2PdHx may reflect a smearing of energy levels in the disordered phases. The proton rotating-frame relaxation times for Ti1-yCuyHx indicate both crystal structure and hydrogen site occupancies greatly influence diffusion behavior. A significant enhancement in hydrogen mobility for amorphous a-TiCuH1.4 has been confirmed; but, short range order is probably retained in the structure of a-TiCuH1.4. Reductions in activation energies are observed when octahedral sites exist in the diffusion paths between tetrahedral sites.</p

Cerebrospinal Fluid Proteome Alterations Associated with Neuropsychiatric Symptoms in Cognitive Decline and Alzheimer's Disease

Although neuropsychiatric symptoms (NPS) are common and severely affect older people with cognitive decline, little is known about their underlying molecular mechanisms and relationships with Alzheimer's disease (AD). The aim of this study was to identify and characterize cerebrospinal fluid (CSF) proteome alterations related to NPS. In a longitudinally followed-up cohort of subjects with normal cognition and patients with cognitive impairment (MCI and mild dementia) from a memory clinic setting, we quantified a panel of 790 proteins in CSF using an untargeted shotgun proteomic workflow. Regression models and pathway enrichment analysis were used to investigate protein alterations related to NPS, and to explore relationships with AD pathology and cognitive decline at follow-up visits. Regression analysis selected 27 CSF proteins associated with NPS. These associations were independent of the presence of cerebral AD pathology (defined as CSF p-tau181/Aβ1-42 &gt; 0.0779, center cutoff). Gene ontology enrichment showed abundance alterations of proteins related to cell adhesion, immune response, and lipid metabolism, among others, in relation to NPS. Out of the selected proteins, three were associated with accelerated cognitive decline at follow-up visits after controlling for possible confounders. Specific CSF proteome alterations underlying NPS may both represent pathophysiological processes independent from AD and accelerate clinical disease progression. Keywords: Alzheimer’s disease; cognitive decline; proteom

Explanation for Anomalous Shock Temperatures Measured by Neutron Resonance Spectroscopy

Neutron resonance spectrometry (NRS) has been used to measure the temperature inside Mo samples during shock loading. The temperatures obtained were significantly higher than predicted assuming ideal hydrodynamic loading. The effect of plastic flow and non-ideal projectile behavior were assessed. Plastic flow was calculated self-consistently with the shock jump conditions: this is necessary for a rigorous estimate of the locus of shock states accessible. Plastic flow was estimated to contribute a temperature rise of 53K compared with hydrodynamic flow. Simulations were performed of the operation of the explosively-driven projectile system used to induce the shock in the Mo sample. The simulations predicted that the projectile was significantly curved on impact, and still accelerating. The resulting spatial variations in load, including radial components of velocity, were predicted to increase the apparent temperature that would be deduced from the width of the neutron resonance by 160K. These corrections are sufficient to reconcile the apparent temperatures deduced using NRS with the accepted properties of Mo, in particular its equation of state.Comment: near-final version, waiting for final consent from an autho

Systemic and central nervous system neuroinflammatory signatures of neuropsychiatric symptoms and related cognitive decline in older people.

Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer's disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical disease progression. We quantified a panel of 38 neuroinflammation and vascular injury markers in paired serum and cerebrospinal fluid (CSF) samples in a cohort of cognitively normal and impaired older subjects. We performed neuropsychiatric and cognitive evaluations and measured CSF biomarkers of AD pathology. Multivariate analysis determined serum and CSF neuroinflammatory alterations associated with NPS, considering cognitive status, AD pathology, and cognitive decline at follow-up visits. NPS were associated with distinct inflammatory profiles in serum, involving eotaxin-3, interleukin (IL)-6 and C-reactive protein (CRP); and in CSF, including soluble intracellular cell adhesion molecule-1 (sICAM-1), IL-8, 10-kDa interferon-γ-induced protein, and CRP. AD pathology interacted with CSF sICAM-1 in association with NPS. Presenting NPS was associated with subsequent cognitive decline which was mediated by CSF sICAM-1. Distinct systemic and CNS inflammatory processes are involved in the pathophysiology of NPS in older people. Neuroinflammation may explain the link between NPS and more rapid clinical disease progression

Landau Gauge Fixing on GPUs

In this paper we present and explore the performance of Landau gauge fixing in GPUs using CUDA. We consider the steepest descent algorithm with Fourier acceleration, and compare the GPU performance with a parallel CPU implementation. Using $32^4$ lattice volumes, we find that the computational power of a single Tesla C2070 GPU is equivalent to approximately 256 CPU cores.Comment: 10 pages, 3 figures and 3 table

REVOLUTA regulates meristem initiation at lateral positions

While the shoot apical meristem (SAM) is indirectly responsible for the initiation of all above-ground postembryonic organs, in most plants the vast majority of these organs are directly initiated by lateral meristems. In Arabidopsis thaliana , the lateral meristems include flower meristems (FMs), which form on the flanks of the SAM, and lateral shoot meristems (LSMs), which develop in leaf axils. While significant progress has been made on the molecular genetic basis of SAM initiation during embryo development, relatively little is known about the initiation of meristems at lateral positions. Here we have characterized the phenotypic consequences and genetic interactions of mutations in the REVOLUTA ( REV ) gene, with an emphasis on the role of REV in lateral meristem initiation. Our observations indicate that REV is required for initiation of both LSMs and FMs, and likely acts in the same pathway as, and upstream of, known meristem regulators. We identified the REV gene and found it encodes a predicted homeodomain leucine zipper transcription factor that also contains a START sterol-lipid binding domain. REV is the same as the IFL gene. REV was expressed at the earliest stages of LSM and FM formation. Within the inflorescence shoot meristem, REV expression appeared to predict 3 5 incipient flower primordia on the flanks of the SAM, and REV expression at stage 1 and stage 2 matched that of WUS and STM , respectively. We propose that REV acts at lateral positions to activate the expression of known meristem regulators.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75526/1/j.1365-313X.2001.00959.x.pd

estMOI: estimating multiplicity of infection using parasite deep sequencing data.

Individuals living in endemic areas generally harbour multiple parasite strains. Multiplicity of infection (MOI) can be an indicator of immune status and transmission intensity. It has a potentially confounding effect on a number of population genetic analyses, which often assume isolates are clonal. Polymerase chain reaction-based approaches to estimate MOI can lack sensitivity. For example, in the human malaria parasite Plasmodium falciparum, genotyping of the merozoite surface protein (MSP1/2) genes is a standard method for assessing MOI, despite the apparent problem of underestimation. The availability of deep coverage data from massively parallizable sequencing technologies means that MOI can be detected genome wide by considering the abundance of heterozygous genotypes. Here, we present a method to estimate MOI, which considers unique combinations of polymorphisms from sequence reads. The method is implemented within the estMOI software. When applied to clinical P.falciparum isolates from three continents, we find that multiple infections are common, especially in regions with high transmission

A subsystems approach for parameter estimation of ODE models of hybrid systems

We present a new method for parameter identification of ODE system descriptions based on data measurements. Our method works by splitting the system into a number of subsystems and working on each of them separately, thereby being easily parallelisable, and can also deal with noise in the observations.Comment: In Proceedings HSB 2012, arXiv:1208.315