Simulation of the secondary electrons energy deposition produced by proton beams in PMMA: influence of the target electronic excitation description

We have studied the radial dependence of the energy deposition of the secondary electron generated by swift proton beams incident with energies T = 50 keV–5 MeV on poly(methylmethacrylate) (PMMA). Two different approaches have been used to model the electronic excitation spectrum of PMMA through its energy loss function (ELF), namely the extended-Drude ELF and the Mermin ELF. The singly differential cross section and the total cross section for ionization, as well as the average energy of the generated secondary electrons, show sizeable differences at T ⩽ 0.1 MeV when evaluated with these two ELF models. In order to know the radial distribution around the proton track of the energy deposited by the cascade of secondary electrons, a simulation has been performed that follows the motion of the electrons through the target taking into account both the inelastic interactions (via electronic ionizations and excitations as well as electron-phonon and electron trapping by polaron creation) and the elastic interactions. The radial distribution of the energy deposited by the secondary electrons around the proton track shows notable differences between the simulations performed with the extended-Drude ELF or the Mermin ELF, being the former more spread out (and, therefore, less peaked) than the latter. The highest intensity and sharpness of the deposited energy distributions takes place for proton beams incident with T ~ 0.1–1 MeV. We have also studied the influence in the radial distribution of deposited energy of using a full energy distribution of secondary electrons generated by proton impact or using a single value (namely, the average value of the distribution); our results show that differences between both simulations become important for proton energies larger than ~0.1 MeV. The results presented in this work have potential applications in materials science, as well as hadron therapy (due to the use of PMMA as a tissue phantom) in order to properly consider the generation of electrons by proton beams and their subsequent transport and energy deposition through the target in nanometric scales.

Derivation of the spin Hamiltonians for Fe in MgO

A method to calculate the effective spin Hamiltonian for a transition metal impurity in a non-magnetic insulating host is presented and applied to the paradigmatic case of Fe in MgO. In the first step we calculate the electronic structure employing standard density functional theory (DFT), based on generalized gradient approximation (GGA), using plane waves as a basis set. The corresponding basis of atomic-like maximally localized Wannier functions is derived and used to represent the DFT Hamiltonian, resulting in a tight-binding model for the atomic orbitals of the magnetic impurity. The third step is to solve, by exact numerical diagonalization, the N electron problem in the open shell of the magnetic atom, including both effects of spin–orbit and Coulomb repulsion. Finally, the low energy sector of this multi-electron Hamiltonian is mapped into effective spin models that, in addition to the spin matrices S, can also include the orbital angular momentum L when appropriate. We successfully apply the method to Fe in MgO, considering both the undistorted and Jahn–Teller (JT) distorted cases. Implications for the influence of Fe impurities on the performance of magnetic tunnel junctions based on MgO are discussed.

Rôle de l'isoforme p35 de la chaîne invariante humaine dans la formation et le transport de complexes de CMH II

La présentation antigénique par les molécules de classe II du complexe majeur d’histocompatibilité (CMH II) est un mécanisme essentiel au contrôle des pathogènes par le système immunitaire. Le CMH II humain existe en trois isotypes, HLA-DP, DQ et DR, tous des hétérodimères composés d’une chaîne α et d’une chaîne β. Le CMH II est entre autres exprimé à la surface des cellules présentatrices d’antigènes (APCs) et des cellules épithéliales activées et a pour fonction de présenter des peptides d’origine exogène aux lymphocytes T CD4+. L’oligomérisation et le trafic intracellulaire du CMH II sont largement facilités par une chaperone, la chaîne invariante (Ii). Il s’agit d’une protéine non-polymorphique de type II. Après sa biosynthèse dans le réticulum endoplasmique (ER), Ii hétéro- ou homotrimérise, puis interagit via sa région CLIP avec le CMH II pour former un complexe αβIi. Le complexe sort du ER pour entamer son chemin vers différents compartiments et la surface cellulaire. Chez l’homme, quatre isoformes d’Ii sont répertoriées : p33, p35, p41 et p43. Les deux isoformes exprimées de manière prédominante, Iip33 et p35, diffèrent par une extension N-terminale de 16 acides aminés portée par Iip35. Cette extension présente un motif de rétention au réticulum endoplasmique (ERM) composé des résidus RXR. Ce motif doit être masqué par la chaîne β du CMH II pour permettre au complexe de quitter le ER. Notre groupe s’est intéressé au mécanisme du masquage et au mode de sortie du ER des complexes αβIi. Nous montrons ici que l’interaction directe, ou en cis, entre la chaîne β du CMH II et Iip35 dans une structure αβIi est essentielle pour sa sortie du ER, promouvant la formation de structures de haut niveau de complexité. Par ailleurs, nous démontrons que NleA, un facteur de virulence bactérien, permet d’altérer le trafic de complexes αβIi comportant Iip35. Ce phénotype est médié par l’interaction entre p35 et les sous-unités de COPII. Bref, Iip35 joue un rôle central dans la formation des complexes αβIi et leur transport hors du ER. Ceci fait d’Iip35 un régulateur clef de la présentation antigénique par le CMH II.

Establishment of a confluent monolayer model with human primary trophoblast cells: novel insights into placental glucose transport

STUDY HYPOTHESIS Using optimized conditions, primary trophoblast cells isolated from human term placenta can develop a confluent monolayer in vitro, which morphologically and functionally resembles the microvilli structure found in vivo. STUDY FINDING We report the successful establishment of a confluent human primary trophoblast monolayer using pre-coated polycarbonate inserts, where the integrity and functionality was validated by cell morphology, biophysical features, cellular marker expression and secretion, and asymmetric glucose transport. WHAT IS KNOWN ALREADY Human trophoblast cells form the initial barrier between maternal and fetal blood to regulate materno-fetal exchange processes. Although the method for isolating pure human cytotrophoblast cells was developed almost 30 years ago, a functional in vitro model with primary trophoblasts forming a confluent monolayer is still lacking. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Human term cytotrophoblasts were isolated by enzymatic digestion and density gradient separation. The purity of the primary cells was evaluated by flow cytometry using the trophoblast-specific marker cytokeratin 7, and vimentin as an indicator for potentially contaminating cells. We screened different coating matrices for high cell viability to optimize the growth conditions for primary trophoblasts on polycarbonate inserts. During culture, cell confluency and polarity were monitored daily by determining transepithelial electrical resistance (TEER) and permeability properties of florescent dyes. The time course of syncytia-related gene expression and hCG secretion during syncytialization were assessed by quantitative RT-PCR and enzyme-linked immunosorbent assay, respectively. The morphology of cultured trophoblasts after 5 days was determined by light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Membrane makers were visualized using confocal microscopy. Additionally, glucose transport studies were performed on the polarized trophoblasts in the same system. MAIN RESULTS AND THE ROLE OF CHANCE During 5-day culture, the highly pure trophoblasts were cultured on inserts coated with reconstituted basement membrane matrix . They exhibited a confluent polarized monolayer, with a modest TEER and a size-dependent apparent permeability coefficient (Papp) to fluorescently labeled compounds (MW ∼400-70 000 Da). The syncytialization progress was characterized by gradually increasing mRNA levels of fusogen genes and elevating hCG secretion. SEM analyses confirmed a confluent trophoblast layer with numerous microvilli, and TEM revealed a monolayer with tight junctions. Immunocytochemistry on the confluent trophoblasts showed positivity for the cell-cell adhesion molecule E-cadherin, the tight junction protein 1 (ZO-1) and the membrane proteins ATP-binding cassette transporter A1 (ABCA1) and glucose transporter 1 (GLUT1). Applying this model to study the bidirectional transport of a non-metabolizable glucose derivative indicated a carrier-mediated placental glucose transport mechanism with asymmetric kinetics. LIMITATIONS, REASONS FOR CAUTION The current study is only focused on primary trophoblast cells isolated from healthy placentas delivered at term. It remains to be evaluated whether this system can be extended to pathological trophoblasts isolated from diverse gestational diseases. WIDER IMPLICATIONS OF THE FINDINGS These findings confirmed the physiological properties of the newly developed human trophoblast barrier, which can be applied to study the exchange of endobiotics and xenobiotics between the maternal and fetal compartment, as well as intracellular metabolism, paracellular contributions and regulatory mechanisms influencing the vectorial transport of molecules. LARGE-SCALE DATA Not applicable. STUDY FUNDING AND COMPETING INTERESTS This study was supported by the Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland, and the Swiss National Science Foundation (grant no. 310030_149958, C.A.). All authors declare that their participation in the study did not involve factual or potential conflicts of interests.

Orientation of biological cells using plane-polarized gaussian beam optical tweezers

Optical tweezers are widely used for the manipulation of cells and their internal structures. However, the degree of manipulation possible is limited by poor control over the orientation of the trapped cells. We show that it is possible to controllably align or rotate disc-shaped cells-chloroplasts of Spinacia oleracea-in a plane-polarized Gaussian beam trap, using optical torques resulting predominantly from circular polarization induced in the transmitted beam by the non-spherical shape of the cells.

Charge transport in a quantum electromechanical system

We describe a quantum electromechanical system comprising a single quantum dot harmonically bound between two electrodes and facilitating a tunneling current between them. An example of such a system is a fullerene molecule between two metal electrodes [Park et al., Nature 407, 57 (2000)]. The description is based on a quantum master equation for the density operator of the electronic and vibrational degrees of freedom and thus incorporates the dynamics of both diagonal (population) and off diagonal (coherence) terms. We derive coupled equations of motion for the electron occupation number of the dot and the vibrational degrees of freedom, including damping of the vibration and thermo-mechanical noise. This dynamical description is related to observable features of the system including the stationary current as a function of bias voltage

Polarized trafficking of E-cadherin is regulated by Rac1 and Cdc42 in Madin-Darby canine kidney cells

E-cadherin is a major cell-cell adhesion protein of epithelia that is trafficked to the basolateral cell surface in a polarized fashion. The exact post-Golgi route and regulation of E-cadherin transport have not been fully described. The Rho GTPases Cdc42 and Rac1 have been implicated in many cell functions, including the exocytic trafficking of other proteins in polarized epithelial cells. These Rho family proteins are also associated with the cadherin-catenin complexes at the cell surface. We have used functional mutants of Rac1 and Cdc42 and inactivating toxins to demonstrate specific roles for both Cdc42 and Rac1 in the post-Golgi transport of E-cadherin. Dominant-negative mutants of Cdc42 and Rac1 accumulate E-cadherin at a distinct post-Golgi step. This accumulation occurs before p120(ctn) interacts with E-cadherin, because p120(ctn) localization was not affected by the Cdc42 or Rac1 mutants. Moreover, the GTPase mutants had no effect on the trafficking of a targeting mutant of E-cadherin, consistent with the selective involvement of Cdc42 and Rac1 in basolateral trafficking. These results provide a new example of Rho GTPase regulation of basolateral trafficking and demonstrate novel roles for Cdc42 and Rac1 in the post-Golgi transport of E-cadherin.

Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin

E-cadherin plays an essential role in cell polarity and cell-cell adhesion; however, the pathway for delivery of E-cadherin to the basolateral membrane of epithelial cells has not been fully characterized. We first traced the post-Golgi, exocytic transport of GFP-tagged E-cadherin (Ecad-GFP) in unpolarized cells. In live cells, Ecad-GFP was found to exit the Golgi complex in pleiomorphic tubulovesicular carriers, which, instead of moving directly to the cell surface, most frequently fused with an intermediate compartment, subsequently identified as a Rab11-positive recycling endosome. In MDCK cells, basolateral targeting of E-cadherin relies on a dileucine motif. Both E-cadherin and a targeting mutant, Delta S1-E-cadherin, colocalized with Rab11 and fused with the recycling endosome before diverging to basolateral or apical membranes, respectively. In polarized and unpolarized cells, coexpression of Rab11 mutants disrupted the cell surface delivery of E-cadherin and caused its mistargeting to the apical membrane, whereas apical Delta S1-E-cadherin was unaffected. We thus demonstrate a novel pathway for Rab11 dependent, dileucine-mediated, mu 1B-independent sorting and basolateral trafficking, exemplified by E-cadherin. The recycling endosome is identified as an intermediate compartment for the post-Golgi trafficking and exocytosis of E-cadherin, with a potentially important role in establishing and maintaining cadherin-based adhesion.

New insights into the interactions of serum proteins with bis(maltolato)oxovanadium(IV): Transport and biotransformation of insulin-enhancing vanadium pharmaceuticals

Significant new insights into the interactions of the potent insulin-enhancing compound bis(maltolato)oxovanadium(IV) (BMOV) with the serum proteins, apo-transferrin and albumin, are presented. Identical reaction products are observed by electron paramagnetic resonance (EPR) with either BMOV or vanadyl sulfate (VOSO4) in solutions of human serum apo-transferrin. Further detailed study rules out the presence of a ternary ligand-vanadyl-transferrin complex proposed previously. By contrast, differences in reaction products are observed for the interactions of BMOV and VOSO4 with human serum albumin (HSA), wherein adduct formation between albumin and BMOV is detected. In BMOV-albumin solutions, vanadyl ions are bound in a unique manner not observed in comparable solutions Of VOSO4 and albumin. Presentation of chelated vanadyl ions precludes binding at the numerous nonspecific sites and produces a unique EPR spectrum which is assigned to a BMOV-HSA adduct. The adduct species cannot be produced, however, from a solution Of VOSO4 and HSA titrated with maltol. Addition of maltol to a VOSO4-HSA solution instead results in formation of a different end product which has been assigned as a ternary complex, VO(ma)(HSA). Furthermore, analysis of solution equilibria using a model system of BMOV with 1-methylimidazole (formation constant log K = 4.5(1), by difference electronic absorption spectroscopy) lends support to an adduct binding mode (VO(ma)(2)-HSA) proposed herein for BMOV and HSA. This detailed report of an in vitro reactivity difference between VOSO4 and BMOV may have bearing on the form of active vanadium metabolites delivered to target tissues. Albumin binding of vanadium chelates is seen to have a potentially dramatic effect on pharmacokinetics, transport, and efficacy of these antidiabetic chelates.

Optimization of pipeline transport for CO2 sequestration

Coal fired power generation will continue to provide energy to the world for the foreseeable future. However, this energy use is a significant contributor to increased atmospheric CO2 concentration and, hence, global warming. Capture and disposal Of CO2 has received increased R&D attention in the last decade as the technology promises to be the most cost effective for large scale reductions in CO2 emissions. This paper addresses CO2 transport via pipeline from capture site to disposal site, in terms of system optimization, energy efficiency and overall economics. Technically, CO2 can be transported through pipelines in the form of a gas, a supercritical. fluid or in the subcooled liquid state. Operationally, most CO2 pipelines used for enhanced oil recovery transport CO2 as a supercritical fluid. In this paper, supercritical fluid and subcooled liquid transport are examined and compared, including their impacts on energy efficiency and cost. Using a commercially available process simulator, ASPEN PLUS 10.1, the results show that subcooled liquid transport maximizes the energy efficiency and minimizes the Cost Of CO2 transport over long distances under both isothermal and adiabatic conditions. Pipeline transport of subcooled liquid CO2 can be ideally used in areas of cold climate or by burying and insulating the pipeline. In very warm climates, periodic refrigeration to cool the CO2 below its critical point of 31.1 degrees C, may prove economical. Simulations have been used to determine the maximum safe pipeline distances to subsequent booster stations as a function of inlet pressure, environmental temperature and ground level heat flux conditions. (c) 2005 Published by Elsevier Ltd.

Anisotropic scattering and anomalous normal-state transport in a high-temperature superconductor

The metallic state of high-temperature copper-oxide superconductors, characterized by unusual and distinct temperature dependences in the transport properties(1-4), is markedly different from that of textbook metals. Despite intense theoretical efforts(5-11), our limited understanding is impaired by our inability to determine experimentally the temperature and momentum dependence of the transport scattering rate. Here, we use a powerful magnetotransport probe to show that the resistivity and the Hall coefficient in highly doped Tl2Ba2CuO6+delta originate from two distinct inelastic scattering channels. One channel is due to conventional electron electron scattering; the other is highly anisotropic, has the same symmetry as the superconducting gap and a magnitude that grows approximately linearly with temperature. The observed form and anisotropy place tight constraints on theories of the metallic state. Moreover, in heavily doped non-superconducting La2-xSrxCuO4, this anisotropic scattering term is absent(12), suggesting an intimate connection between the origin of this scattering and superconductivity itself.

Strong electronic correlations in superconducting organic charge transfer salts

We review the role of strong electronic correlations in quasi-two-dimensional organic charge transfer salts such as (BEDT-TTF)(2)X, (BETS)(2)Y, and beta'-[Pd(dmit)(2)](2)Z. We begin by defining minimal models for these materials. It is necessary to identify two classes of material: the first class is strongly dimerized and is described by a half-filled Hubbard model; the second class is not strongly dimerized and is described by a quarter-filled extended Hubbard model. We argue that these models capture the essential physics of these materials. We explore the phase diagram of the half-filled quasi-two-dimensional organic charge transfer salts, focusing on the metallic and superconducting phases. We review work showing that the metallic phase, which has both Fermi liquid and 'bad metal' regimes, is described both quantitatively and qualitatively by dynamical mean field theory (DMFT). The phenomenology of the superconducting state is still a matter of contention. We critically review the experimental situation, focusing on the key experimental results that may distinguish between rival theories of superconductivity, particularly probes of the pairing symmetry and measurements of the superfluid stiffness. We then discuss some strongly correlated theories of superconductivity, in particular the resonating valence bond (RVB) theory of superconductivity. We conclude by discussing some of the major challenges currently facing the field. These include parameterizing minimal models, the evidence for a pseudogap from nuclear magnetic resonance (NMR) experiments, superconductors with low critical temperatures and extremely small superfluid stiffnesses, the possible spin- liquid states in kappa-(ET)(2)Cu-2(CN)(3) and beta'-[Pd(dmit)(2)](2)Z, and the need for high quality large single crystals.

Excitation spectra of the spin-1/2 triangular-lattice Heisenberg antiferromagnet

We use series expansion methods to calculate the dispersion relation of the one-magnon excitations for the spin-(1)/(2) triangular-lattice nearest-neighbor Heisenberg antiferromagnet above a three-sublattice ordered ground state. Several striking features are observed compared to the classical (large-S) spin-wave spectra. Whereas, at low energies the dispersion is only weakly renormalized by quantum fluctuations, significant anomalies are observed at high energies. In particular, we find rotonlike minima at special wave vectors and strong downward renormalization in large parts of the Brillouin zone, leading to very flat or dispersionless modes. We present detailed comparison of our calculated excitation energies in the Brillouin zone with the spin-wave dispersion to order 1/S calculated recently by Starykh, Chubukov, and Abanov [Phys. Rev. B74, 180403(R) (2006)]. We find many common features but also some quantitative and qualitative differences. We show that at temperatures as low as 0.1J the thermally excited rotons make a significant contribution to the entropy. Consequently, unlike for the square lattice model, a nonlinear sigma model description of the finite-temperature properties is only applicable at temperatures < 0.1J. Finally, we review recent NMR measurements on the organic compound kappa-(BEDT-TTF)(2)Cu-2(CN)(3). We argue that these are inconsistent with long-range order and a description of the low-energy excitations in terms of interacting magnons, and that therefore a Heisenberg model with only nearest-neighbor exchange does not offer an adequate description of this material.

Electrolyte transport in the mammalian colon: mechanisms and implications for disease Kunzelmann and Marcus Mall

Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease. Physiol. Rev. 82: 245-289, 2002.The colonic epithelium has both absorptive and secretory functions. The transport is characterized by a net absorption of NaCl, short-chain fatty acids (SCFA), and water, allowing extrusion of a feces with very little water and salt content. In addition, the epithelium does secret mucus, bicarbonate, and KCl. Polarized distribution of transport proteins in both luminal and basolateral membranes enables efficient salt transport in both directions, probably even within an individual cell. Meanwhile, most of the participating transport proteins have been identified, and their function has been studied in detail. Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na+ channels (ENaC), the Na+-K+-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK. Acute regulation of absorption may occur by a Na+ feedback mechanism and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl- secretion in the adult colon relies on luminal CFTR, which is a cAMP-regulated Cl- channel and a regulator of other transport proteins. As a consequence, mutations in CFTR result in both impaired Cl- secretion and enhanced Na+ absorption in the colon of cystic fibrosis (CF) patients. Ca2+- and cAMP-activated basolateral K+ channels support both secretion and absorption of electrolytes and work in concert with additional regulatory proteins, which determine their functional and pharmacological profile. Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea. It will also lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma.