Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-g production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses

The regulation of IL-10 expression

Interleukin (IL)-10 is an important immunoregulatory cytokine and an understanding of how IL-10 expression is controlled is critical in the design of immune intervention strategies. IL-10 is produced by almost all cell types within the innate (including macrophages, monocytes, dendritic cells (DCs), mast cells, neutrophils, eosinophils and natural killer cells) and adaptive (including CD4(+) T cells, CD8(+) T cells and B cells) immune systems. The mechanisms of IL-10 regulation operate at several stages including chromatin remodelling at the Il10 locus, transcriptional regulation of Il10 expression and post-transcriptional regulation of Il10 mRNA. In addition, whereas some aspects of Il10 gene regulation are conserved between different immune cell types, several are cell type- or stimulus-specific. Here, we outline the complexity of IL-10 production by discussing what is known about its regulation in macrophages, monocytes, DCs and CD4(+) T helper cells

Measurement of ultrashort laser pulses using single-crystal films of 4-aminobenzophenone

Single-crystal thin-film of an organic second-order nonlinear optical material, 4-aminobenzophenone (ABP), is used to measure the pulsewidth of a Ti-Sapphire laser producing ~45 fs pulses at 1 kHz repetition rate, by the non-collinear second-harmonic generation (SHG) intensity autocorrelation technique. These films are suitable for measurements over a broad wavelength range, down to 780 nm, due to their wide optical transparency. The single-crystal film with thickness (~3 μ m) less than the coherence length requires no phase-matching for efficient broadband SHG. Pulse walk-off due to group-velocity mismatch (GVM) and temporal broadening of the pulses due to group-velocity dispersion (GVD) are found to be negligible. These effects have been estimated for pulse width down to few-cycle pulses (~10 fs), and the analyses show that these films can be used to characterize such ultrashort optical pulses

The effects of phosphorus at the SiO2/4H-SiC interface

Phosphorus passivation of the SiO2/4H-SiC interface lowers the interface trap density and increases the field effect mobility for N-channel MOSFETs to twice the value of 30-40cm2/V-s obtained using standard NO nitridation. Passivation using P2O5 introduced with an SiP2O7 planar diffusion source (PDS) converts the oxide layer to phosphosilicate glass (PSG) which is a polar material. BTS (bias-temperature-stress) measurements with MOS capacitors and FETs show that the benefits of reduced interface trap density and increased mobility are offset by unstable flat band and threshold voltages. This instability can be removed by etching away the PSG oxide and depositing a replacement SiO2 layer. However, trap densities for etched MOS capacitors are NO-like (i.e., higher), which would lead one to expect a lower mobility if MOSFETs are fabricated with the PSG / etch / deposited oxide process. © (2012) Trans Tech Publications

Phosphorous passivation of the SiO 2/4H-SiC interface

We describe experimental and theoretical studies to determine the effects of phosphorous as a passivating agent for the SiO 2/4H-SiC interface. Annealing in a P 2O 5 ambient converts the SiO 2 layer to PSG (phosphosilicate glass) which is known to be a polar material. Higher mobility (approximately twice the value of 30-40 cm 2/V s obtained using nitrogen introduced with an anneal in nitric oxide) and lower threshold voltage are compatible with a lower interface defect density. Trap density, current-voltage and bias-temperature stress (BTS) measurements for MOS capacitors are also discussed. The BTS measurements point to the possibility of an unstable MOSFET threshold voltage caused by PSG polarization charge at the O-S interface. Theoretical considerations suggest that threefold carbon atoms at the interface can be passivated by phosphorous which leads to a lower interface trap density and a higher effective mobility for electrons in the channel. The roles of phosphorous in the passivation of correlated carbon dangling bonds, for SiC counter-doping, for interface band-tail state suppression, for Na-like impurity band formation and for substrate trap passivation are also discussed briefly. © 2011 Elsevier Ltd. All rights reserved

Thin PSG process for 4H-SiC MOSFET

The use of phosphorous as a passivating agent for the SiO2/4H-SiC interface increases the field effect channel mobility of 4H-SiC MOSFET to twice the value, 30-40cm2/V-s, that is obtained with a high temperature anneal in nitric oxide (NO). A solid SiP2O7 planar diffusion source is used to produce P2O5 for the passivation of the interface. Incorporation of phosphorous into SiO2 leads to formation of phosphosilicate glass (PSG) which is known to be a polar material causes device instability. With a new modified thin phosphorous (P) passivation process, as described in this abstract, we can improve the stability of MOSFETs significantly with mobility around 75cm2/V.s