Replica Field Theory for Deterministic Models (II): A Non-Random Spin Glass with Glassy Behavior

We introduce and study a model which admits a complex landscape without containing quenched disorder. Continuing our previous investigation we introduce a disordered model which allows us to reconstruct all the main features of the original phase diagram, including a low $T$ spin glass phase and a complex dynamical behavior.Comment: 35 pages with uu figures, Roma 102

Interleukin-35-Producing CD8α(+) Dendritic Cells Acquire a Tolerogenic State and Regulate T Cell Function.

Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10. Vaccination of mice with IL-35-expressing DCs promoted tumor growth and reduced the severity of autoimmune encephalitis not only in a preventive but also after induction of encephalitogenic T cells. The reduction in experimental autoimmune encephalitis severity was significantly more pronounced when antigen-pulsed IL-35(+) DCs were used. These findings suggest a new, indirect effector mechanism by which IL-35-responding antigen-presenting cells contribute to immune tolerance. Furthermore, IL-35-transfected DCs may be a promising approach for immunotherapy in the context of autoimmune diseases

Finite-Connectivity Spin-Glass Phase Diagrams and Low Density Parity Check Codes

We obtain phase diagrams of regular and irregular finite connectivity spin-glasses. Contact is firstly established between properties of the phase diagram and the performances of low density parity check codes (LDPC) within the Replica Symmetric (RS) ansatz. We then study the location of the dynamical and critical transition of these systems within the one step Replica Symmetry Breaking theory (RSB), extending similar calculations that have been performed in the past for the Bethe spin-glass problem. We observe that, away from the Nishimori line, in the low temperature region, the location of the dynamical transition line does change within the RSB theory, in comparison with the (RS) case. For LDPC decoding over the binary erasure channel we find, at zero temperature and rate R=1/4 an RS critical transition point located at p_c = 0.67 while the critical RSB transition point is located at p_c = 0.7450, to be compared with the corresponding Shannon bound 1-R. For the binary symmetric channel (BSC) we show that the low temperature reentrant behavior of the dynamical transition line, observed within the RS ansatz, changes within the RSB theory; the location of the dynamical transition point occurring at higher values of the channel noise. Possible practical implications to improve the performances of the state-of-the-art error correcting codes are discussed.Comment: 21 pages, 15 figure

Ensemble prediction for nowcasting with a convection-permitting model - II: forecast error statistics

A 24-member ensemble of 1-h high-resolution forecasts over the Southern United Kingdom is used to study short-range forecast error statistics. The initial conditions are found from perturbations from an ensemble transform Kalman filter. Forecasts from this system are assumed to lie within the bounds of forecast error of an operational forecast system. Although noisy, this system is capable of producing physically reasonable statistics which are analysed and compared to statistics implied from a variational assimilation system. The variances for temperature errors for instance show structures that reflect convective activity. Some variables, notably potential temperature and specific humidity perturbations, have autocorrelation functions that deviate from 3-D isotropy at the convective-scale (horizontal scales less than 10 km). Other variables, notably the velocity potential for horizontal divergence perturbations, maintain 3-D isotropy at all scales. Geostrophic and hydrostatic balances are studied by examining correlations between terms in the divergence and vertical momentum equations respectively. Both balances are found to decay as the horizontal scale decreases. It is estimated that geostrophic balance becomes less important at scales smaller than 75 km, and hydrostatic balance becomes less important at scales smaller than 35 km, although more work is required to validate these findings. The implications of these results for high-resolution data assimilation are discussed

Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27)

Aims/hypothesis: Non-invasive diagnostic tools specific for pancreatic beta cells will have a profound impact on our understanding of the pathophysiology of metabolic diseases such as diabetes. The objective of this study was to use molecular imaging probes specifically targeting beta cells on human samples and animal models using state-of-the-art imaging modalities (fluorescence and PET) with preclinical and clinical perspective. Methods: We generated a monoclonal antibody, 8/9-mAb, targeting transmembrane protein 27 (TMEM27; a surface N-glycoprotein that is highly expressed on beta cells), compared its expression in human and mouse pancreas, and demonstrated beta cell-specific binding in both. In vivo imaging was performed in mice with subcutaneous insulinomas overexpressing the human TMEM27 gene, or transgenic mice with beta cell-specific hTMEM27 expression under the control of rat insulin promoter (RIP-hTMEM27-tg), using fluorescence and radioactively labelled antibody, followed by tissue ex vivo analysis and fluorescence microscopy. Results: Fluorescently labelled 8/9-mAb showed beta cell-specific staining on human and mouse pancreatic sections. Real-time PCR on islet cDNA indicated about tenfold higher expression of hTMEM27 in RIP-hTMEM27-tg mice than in humans. In vivo fluorescence and PET imaging in nude mice with insulinoma xenografts expressing hTMEM27 showed high 8/9-mAb uptake in tumours after 72h. Antibody homing was also observed in beta cells of RIP-hTMEM27-tg mice by in vivo fluorescence imaging. Ex vivo analysis of intact pancreas and fluorescence microscopy in beta cells confirmed these findings. Conclusions/interpretation: hTMEM27 constitutes an attractive target for in vivo visualisation of pancreatic beta cells. Studies in mouse insulinoma models and mice expressing hTMEM27 demonstrate the feasibility of beta cell-targeted in vivo imaging, which is attractive for preclinical investigations and holds potential in clinical diagnostic

Survey propagation at finite temperature: application to a Sourlas code as a toy model

In this paper we investigate a finite temperature generalization of survey propagation, by applying it to the problem of finite temperature decoding of a biased finite connectivity Sourlas code for temperatures lower than the Nishimori temperature. We observe that the result is a shift of the location of the dynamical critical channel noise to larger values than the corresponding dynamical transition for belief propagation, as suggested recently by Migliorini and Saad for LDPC codes. We show how the finite temperature 1-RSB SP gives accurate results in the regime where competing approaches fail to converge or fail to recover the retrieval state

Cytokines and growth factors cross-link heparan sulfate

The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many soluble extracellular signalling molecules such as chemokines and growth factors, and regulates their transport and effector functions. It is, however, unknown whether upon binding HS these proteins can affect the long-range structure of HS. To test this idea, we interrogated a supramolecular model system, in which HS chains grafted to streptavidin-functionalized oligoethylene glycol monolayers or supported lipid bilayers mimic the HS-rich pericellular or extracellular matrix, with the biophysical techniques quartz crystal microbalance (QCM-D) and fluorescence recovery after photobleaching (FRAP). We were able to control and characterize the supramolecular presentation of HS chains—their local density, orientation, conformation and lateral mobility—and their interaction with proteins. The chemokine CXCL12α (or SDF-1α) rigidified the HS film, and this effect was due to protein-mediated cross-linking of HS chains. Complementary measurements with CXCL12α mutants and the CXCL12γ isoform provided insight into the molecular mechanism underlying cross-linking. Fibroblast growth factor 2 (FGF-2), which has three HS binding sites, was also found to cross-link HS, but FGF-9, which has just one binding site, did not. Based on these data, we propose that the ability to cross-link HS is a generic feature of many cytokines and growth factors, which depends on the architecture of their HS binding sites. The ability to change matrix organization and physico-chemical properties (e.g. permeability and rigidification) implies that the functions of cytokines and growth factors may not simply be confined to the activation of cognate cellular receptors

Damage spreading transition in glasses: a probe for the ruggedness of the configurational landscape

We consider damage spreading transitions in the framework of mode-coupling theory. This theory describes relaxation processes in glasses in the mean-field approximation which are known to be characterized by the presence of an exponentially large number of meta-stable states. For systems evolving under identical but arbitrarily correlated noises we demonstrate that there exists a critical temperature $T_0$ which separates two different dynamical regimes depending on whether damage spreads or not in the asymptotic long-time limit. This transition exists for generic noise correlations such that the zero damage solution is stable at high-temperatures being minimal for maximal noise correlations. Although this dynamical transition depends on the type of noise correlations we show that the asymptotic damage has the good properties of an dynamical order parameter such as: 1) Independence on the initial damage; 2) Independence on the class of initial condition and 3) Stability of the transition in the presence of asymmetric interactions which violate detailed balance. For maximally correlated noises we suggest that damage spreading occurs due to the presence of a divergent number of saddle points (as well as meta-stable states) in the thermodynamic limit consequence of the ruggedness of the free energy landscape which characterizes the glassy state. These results are then compared to extensive numerical simulations of a mean-field glass model (the Bernasconi model) with Monte Carlo heat-bath dynamics. The freedom of choosing arbitrary noise correlations for Langevin dynamics makes damage spreading a interesting tool to probe the ruggedness of the configurational landscape.Comment: 25 pages, 13 postscript figures. Paper extended to include cross-correlation

Tracing the role of human civilization in the globalization of plant pathogens

Acknowledgments. We apologize to all those colleagues whose work was not cited because of space restrictions.Peer reviewedPostprin