Realist Evaluation : an overview

This report summarises the discussions and presentations of the Expert Seminar ‘Realist Evaluation’ with Gill Westhorp, which took place in Wageningen on March 29, 2011. The Expert Seminar was organised by the Wageningen UR Centre for Development Innovation in collaboration with Learning by Design and Context, international cooperation

Hysteresis and bi-stability by an interplay of calcium oscillations and action potential firing

Many cell types exhibit oscillatory activity, such as repetitive action potential firing due to the Hodgkin-Huxley dynamics of ion channels in the cell membrane or reveal intracellular inositol triphosphate (IP$_3$) mediated calcium oscillations (CaOs) by calcium-induced calcium release channels (IP$_3$-receptor) in the membrane of the endoplasmic reticulum (ER). The dynamics of the excitable membrane and that of the IP$_3$-mediated CaOs have been the subject of many studies. However, the interaction between the excitable cell membrane and IP$_3$-mediated CaOs, which are coupled by cytosolic calcium which affects the dynamics of both, has not been studied. This study for the first time applied stability analysis to investigate the dynamic behavior of a model, which includes both an excitable membrane and an intracellular IP$_3$-mediated calcium oscillator. Taking the IP$_3$ concentration as a control parameter, the model exhibits a novel rich spectrum of stable and unstable states with hysteresis. The four stable states of the model correspond in detail to previously reported growth-state dependent states of the membrane potential of normal rat kidney fibroblasts in cell culture. The hysteresis is most pronounced for experimentally observed parameter values of the model, suggesting a functional importance of hysteresis. This study shows that the four growth-dependent cell states may not reflect the behavior of cells that have differentiated into different cell types with different properties, but simply reflect four different states of a single cell type, that is characterized by a single model.Comment: 29 pages, 6 figure

Definition of a Novel Pathway Centered on Lysophosphatidic Acid To Recruit Monocytes during the Resolution Phase of Tissue Inflammation.

Blood-derived monocytes remove apoptotic cells and terminate inflammation in settings as diverse as atherosclerosis and Alzheimer's disease. They express high levels of the proresolving receptor ALX/FPR2, which is activated by the protein annexin A1 (ANXA1), found in high abundance in inflammatory exudates. Using primary human blood monocytes from healthy donors, we identified ANXA1 as a potent CD14+CD16- monocyte chemoattractant, acting via ALX/FPR2. Downstream signaling pathway analysis revealed the p38 MAPK-mediated activation of a calcium independent phospholipase A2 with resultant synthesis of lysophosphatidic acid (LPA) driving chemotaxis through LPA receptor 2 and actin cytoskeletal mobilization. In vivo experiments confirmed ANXA1 as an independent phospholipase A2-dependent monocyte recruiter; congruently, monocyte recruitment was significantly impaired during ongoing zymosan-induced inflammation in AnxA1-/- or alx/fpr2/3-/- mice. Using a dorsal air-pouch model, passive transfer of apoptotic neutrophils between AnxA1-/- and wild-type mice identified effete neutrophils as the primary source of soluble ANXA1 in inflammatory resolution. Together, these data elucidate a novel proresolving network centered on ANXA1 and LPA generation and identify previously unappreciated determinants of ANXA1 and ALX/FPR2 signaling in monocytes

Double Exchange Alone Does Not Explain the Resistivity of La1−xSrxMnO3La_{1-x} Sr_x MnO_3

The $La_{1-x} Sr_x MnO_3$ system with $0.2 \lesssim x \lesssim 0.4$ has traditionally been modelled with a ``double exchange'' Hamiltonian, in which it is assumed that the only relevant physics is the tendency of carrier hopping to line up neighboring spins. We present a solution of the double exchange model, show it is incompatible with many aspects of the resistivity data, and propose that a strong electron-phonon interaction arising from a Jahn-Teller splitting of the outer Mn d-level plays a crucial role.Comment: Figure available via concentional mail. Contact [email protected]

Monte Carlo Simulations for the Magnetic Phase Diagram of the Double Exchange Hamiltonian

We have used Monte Carlo simulation techniques to obtain the magnetic phase diagram of the double exchange Hamiltonian. We have found that the Berry's phase of the hopping amplitude has a negligible effect in the value of the magnetic critical temperature. To avoid finite size problems in our simulations we have also developed an approximated expression for the double exchange energy. This allows us to obtain the critical temperature for the ferromagnetic to paramagnetic transition more accurately. In our calculations we do not observe any strange behavior in the kinetic energy, chemical potential or electron density of states near the magnetic critical temperature. Therefore, we conclude that other effects, not included in the double exchange Hamiltonian, are needed to understand the metal-insulator transition which occurs in the manganites.Comment: 6 pages Revtex, 8 PS figure

An alternative protein targeting pathway in Escherichia coli: studies on the role of FtsY

In Escherichia coli, a signal recognition particle (SRP) has been identified which binds specifically to the signal sequence of presecretory proteins and which appears to be essential for efficient translocation of a subset of proteins. In this study we have investigated the function of E. coli FtsY which shares sequence similarity with the alpha-subunit of the eukaryotic SRP receptor ('docking protein') in the membrane of the endoplasmic reticulum. A strain was constructed which allows the conditional expression of FtsY. Depletion of FtsY is shown to cause the accumulation of the precursor form of beta-lactamase, OmpF and ribose binding protein in vivo, whereas the processing of various other presecretory proteins is unaffected. Furthermore, FtsY-depleted inverted cytoplasmic membrane vesicles are shown to be defective in the translocation of pre-beta-lactamase using an in vitro import assay. Subcellular localization studies revealed that FtsY is located in part at the cytoplasmic membrane with which it seems peripherally associated. These observations suggest that FtsY is the functional E. coli homolog of the mammalian SRP receptor

Charge Localization in Disordered Colossal-Magnetoresistance Manganites

The metallic or insulating nature of the paramagnetic phase of the colossal-magnetoresistance manganites is investigated via a double exchange Hamiltonian with diagonal disorder. Mobility edge trajectory is determined with the transfer matrix method. Density of states calculations indicate that random hopping alone is not sufficient to induce Anderson localization at the Fermi level with 20-30% doping. We argue that the metal-insulator transtion is likely due to the formation of localized polarons from nonuniform extended states as the effective band width is reduced by random hoppings and electron-electron interactions.Comment: 4 pages, RevTex. 4 Figures include

Topological Phase Diagram of a Two-Subband Electron System

We present a phase diagram for a two-dimensional electron system with two populated subbands. Using a gated GaAs/AlGaAs single quantum well, we have mapped out the phases of various quantum Hall states in the density-magnetic filed plane. The experimental phase diagram shows a very different topology from the conventional Landau fan diagram. We find regions of negative differential Hall resistance which are interpreted as preliminary evidence of the long sought reentrant quantum Hall transitions. We discuss the origins of the anomalous topology and the negative differential Hall resistance in terms of the Landau level and subband mixing.Comment: 4 pages, 4 figure

Impact of Charge Ordering on Magnetic Correlations in Perovskite (Bi,Ca)MnO_3

Single crystalline (Bi,Ca)MnO3 (74< %Ca <82) were studied with neutron scattering, electron diffraction and bulk magnetic measurement. We discovered dynamic ferromagnetic spin correlations at high temperatures, which are replaced by antiferromagnetic spin fluctuations at a concomitant charge ordering and structural transition. Our results indicate that thermal-activated hopping of the Jahn-Teller active e_g electrons in these insulating materials, nevertheless, induce ferromagnetic interaction through double-exchange mechanism. It is the ordering of these charges competing with the double-exchange ferromagnetic metallic state.Comment: 11 pages, 3 figures, Revte