Fauna of Testate Amoebae from the Rhytidome of Juglans Nigra

Samples of bark without visible lichen or moss cover were taken from a Juglans nigra located in a city lot in Des Moines, Iowa, remote from water. Euglypha ciliata, E. cuspidata, Microchlamys patella, Centropyxis aerophilus, and two unidentified species of Difflugia were found, ranging from ground level to heights of 35 feet. An estimate of population density, based on a modification of the most probable number count, showed evidence of zonation on the tree surface, with C. aerophilus restricted to near ground level, M. patella occurring approximately evenly up to 35 feet, and E. cuspidata most abundant at moderate heights. Some of the factors related to distribution on the tree surface are discussed

Schistosomal hepatic fibrosis and the interferon gamma receptor: a linkage analysis using single-nucleotide polymorphic markers

A minority of individuals infected with the parasite Schistosoma mansoni develops hepatic fibrosis. HLA studies in Egypt and a candidate gene search in a Sudanese population indicate that the host's genetics contribute to disease susceptibility. In an Egyptian community, 32.7% of individuals 11 years and older had significant fibrosis by WHO ultrasound criteria. Linkage to 10 candidate genes was tested using 89 affected sibling pairs from 40 pedigrees in this community. The candidates included genes that initiate fibrosis, participate in collagen synthesis, or control collagen degradation. Two to four single-nucleotide polymorphisms (SNPs) were genotyped per locus, and 188 individuals were genotyped at 48 markers. Model-free modified Haseman-Elston analysis identified linkage to a SNP in the interferon gamma receptor locus (P ¼ 0.000001). There was also weak evidence for linkage to the interleukin 13-4 region and tissue growth factor beta 1

First Principles Force Field for Metallic Tantalum

We propose a general strategy to develop accurate Force Fields (FF) for metallic systems derived from ab initio quantum mechanical (QM) calculations; we illustrate this approach for tantalum. As input data to the FF we use the linearized augmented plane wave method (LAPW) with the generalized gradient approximation (GGA) to calculate: (i) the zero temperature equation of state (EOS) of Ta for bcc, fcc, and hcp crystal structures for pressures up to ~500 GPa. (ii) Elastic constants. (iii) We use a mixed-basis pseudopotential code to calculate volume relaxed vacancy formation energy also as a function of pressure. In developing the Ta FF we also use previous QM calculations of: (iv) the equation of state for the A15 structure. (v) the surface energy bcc (100). (vi) energetics for shear twinning of the bcc crystal. We find that withappropriate parameters an embedded atom model force field (denoted as qEAM FF) is able to reproduce all this QM data. Thus, the same FF describes with good accuracy the bcc, fcc, hcp and A15 phases of Ta for pressures from ~ -10 GPa to ~ 500 GPa, while also describing the vacancy, surface energy, and shear transformations. The ability of this single FF to describe such a range of systems with a variety of coordinations suggests that it would be accurate for describing defects such as dislocations, grain boundaries, etc. We illustrate the use of the qEAM FF with molecular dynamics to calculate such finite temperature properties as the melting curve up to 300 GPa; we obtain a zero pressure melting temperature of T_(melt)=3150 +/- 50 K in good agreement with experiment (3213-3287 K). We also report on the thermal expansion of Ta in a wide temperature range; our calculated thermal expansivity agrees well with experimental data

Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding

TCR-signaling strength generally correlates with peptide-MHC binding affinity; however, exceptions exist. We find high-affinity, yet non-stimulatory, interactions occur with high frequency in the human T cell repertoire. Here, we studied human TCRs that are refractory to activation by pMHC ligands despite robust binding. Analysis of 3D affinity, 2D dwell time, and crystal structures of stimulatory versus non-stimulatory TCR-pMHC interactions failed to account for their different signaling outcomes. Using yeast pMHC display, we identified peptide agonists of a formerly non-responsive TCR. Single-molecule force measurements demonstrated the emergence of catch bonds in the activating TCR-pMHC interactions, correlating with exclusion of CD45 from the TCR-APC contact site. Molecular dynamics simulations of TCR-pMHC disengagement distinguished agonist from non-agonist ligands based on the acquisition of catch bonds within the TCR-pMHC interface. The isolation of catch bonds as a parameter mediating the coupling of TCR binding and signaling has important implications for TCR and antigen engineering for immunotherapy

Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding

TCR-signaling strength generally correlates with peptide-MHC binding affinity; however, exceptions exist. We find high-affinity, yet non-stimulatory, interactions occur with high frequency in the human T cell repertoire. Here, we studied human TCRs that are refractory to activation by pMHC ligands despite robust binding. Analysis of 3D affinity, 2D dwell time, and crystal structures of stimulatory versus non-stimulatory TCR-pMHC interactions failed to account for their different signaling outcomes. Using yeast pMHC display, we identified peptide agonists of a formerly non-responsive TCR. Single-molecule force measurements demonstrated the emergence of catch bonds in the activating TCR-pMHC interactions, correlating with exclusion of CD45 from the TCR-APC contact site. Molecular dynamics simulations of TCR-pMHC disengagement distinguished agonist from non-agonist ligands based on the acquisition of catch bonds within the TCR-pMHC interface. The isolation of catch bonds as a parameter mediating the coupling of TCR binding and signaling has important implications for TCR and antigen engineering for immunotherapy

INSTITUTE OF PHYSICS PUBLISHING MODELLING AND SIMULATION IN MATERIALS SCIENCE AND ENGINEERING First principles force field for metallic tantalum

Abstract We develop a many-body force field (FF) for tantalum based on extensive ab initio quantum mechanical (QM) calculations and illustrate its application with molecular dynamics (MD). As input data to the FF we use ab initio methods (LAPW-GGA) to calculate: (i) the zero temperature equation of state (EOS) of Ta for bcc, fcc, and hcp crystal structures for pressures up to ∼500 GPa, and (ii) elastic constants. We use a mixed-basis pseudopotential code to calculate: (iii) volume-relaxed vacancy formation energy also as a function of pressure. In developing the Ta FF we also use previous QM calculations of: (iv) the EOS for the A15 structure; (v) the surface energy bcc (100); (vi) energetics for shear twinning of the bcc crystal. We find that, with appropriate parameters, an embedded atom model FF (denoted as qEAM FF) is able to reproduce all this QM data. We illustrate the use of the qEAM FF with MD to calculate such finite temperature properties as the melting curve up to 300 GPa and thermal expansivity in a wide temperature range. Both our predictions agree well with experimental values

A Simplified in vivo Autoradiographic Strategy for the Determination of Regional Cerebral Blood Flow by Positron Emission Tomography: Theoretical Considerations and Validation Studies in the Rat

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= z). Integrated cranial activity C̄B is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that C̄R=∑x=0zAx, where each of the terms Ax is a readily evaluated function of the blood flow rate constant k, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of C̄B vs. k, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBFin vivo = CBFclassical X 0.99 − 0.02 (units in ml g−1 min−1; correlation coefficient r = 0.966)