Rigidity and Non-recurrence along Sequences

Two properties of a dynamical system, rigidity and non-recurrence, are examined in detail. The ultimate aim is to characterize the sequences along which these properties do or do not occur for different classes of transformations. The main focus in this article is to characterize explicitly the structural properties of sequences which can be rigidity sequences or non-recurrent sequences for some weakly mixing dynamical system. For ergodic transformations generally and for weakly mixing transformations in particular there are both parallels and distinctions between the class of rigid sequences and the class of non-recurrent sequences. A variety of classes of sequences with various properties are considered showing the complicated and rich structure of rigid and non-recurrent sequences

Human Dendritic Cell Subsets Undergo Distinct Metabolic Reprogramming for Immune Response

Toll-like receptor (TLR) agonists induce metabolic reprogramming, which is required for immune activation. We have investigated mechanisms that regulate metabolic adaptation upon TLR-stimulation in human blood DC subsets, CD1c+ myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). We show that TLR-stimulation changes expression of genes regulating oxidative phosphorylation (OXPHOS) and glutamine metabolism in pDC. TLR-stimulation increases mitochondrial content and intracellular glutamine in an autophagy-dependent manner in pDC. TLR-induced glutaminolysis fuels OXPHOS in pDCs. Notably, inhibition of glutaminolysis and OXPHOS prevents pDC activation. Conversely, TLR-stimulation reduces mitochondrial content, OXPHOS activity and induces glycolysis in CD1c+ mDC. Inhibition of mitochondrial fragmentation or promotion of mitochondrial fusion impairs TLR-stimulation induced glycolysis and activation of CD1c+ mDCs. TLR-stimulation triggers BNIP3-dependent mitophagy, which regulates transcriptional activity of AMPKα1. BNIP3-dependent mitophagy is required for induction of glycolysis and activation of CD1c+ mDCs. Our findings reveal that TLR stimulation differentially regulates mitochondrial dynamics in distinct human DC subsets, which contributes to their activation

Dynamical effects of the nanometer-sized polarized domains in Pb(Zn1/3Nb2/3)O3

Recent neutron scattering measurements performed on the relaxor ferroelectric Pb[(Zn1/3Nb2/3)0.92Ti0.08]O3 (PZN-8%PT) in its cubic phase at 500 K, have revealed an anomalous ridge of inelastic scattering centered ~0.2 A-1 from the zone center (Gehring et al., Phys. Rev. Lett. 84, 5216 (2000)). This ridge of scattering resembles a waterfall when plotted as a phonon dispersion diagram, and extends vertically from the transverse acoustic (TA) branch near 4 meV to the transverse optic (TO) branch near 9 meV. No zone center optic mode was found. We report new results from an extensive neutron scattering study of pure PZN that exhibits the same waterfall feature. We are able to model the dynamics of the waterfall using a simple coupled-mode model that assumes a strongly q-dependent optic mode linewidth Gamma1(q) that increases sharply near 0.2 A-1 as one approaches the zone center. This model was motivated by the results of Burns and Dacol in 1983, who observed the formation of a randomly-oriented local polarization in PZN at temperatures far above its ferroelectric phase transition temperature. The dramatic increase in Gamma1 is believed to occur when the wavelength of the optic mode becomes comparable to the size of the small polarized micro-regions (PMR) associated with this randomly-oriented local polarization, with the consequence that longer wavelength optic modes cannot propagate and become overdamped. Below Tc=410 K, the intensity of the waterfall diminishes. At lowest temperatures ~30 K the waterfall is absent, and we observe the recovery of a zone center transverse optic mode near 10.5 meV.Comment: 8 pages, 9 figures (one color). Submitted to Physical Review

Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy

Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P. We found that GM-CSF and pRNA had similar effects on their target cells, whereas pRNA and CpG-P induced stronger type I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GM-CSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, the two novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinical-grade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects that are detrimental for vaccine efficacy

Quasi-Elastic Scattering, Random Fields and phonon-coupling effects in PbMg1/3Nb2/3O3

The low-energy part of the vibration spectrum in PbMg$_{1/3}$Nb$_{2/3}$O$_3$ (PMN) relaxor ferroelectric has been studied by neutron scattering above and below the Burns temperature, T$_d$. The transverse acoustic and the lowest transverse optic phonons are strongly coupled and we have obtained a model for this coupling. We observe that the lowest optic branch is always underdamped. A resolution-limited central peak and quasi-elastic scattering appear in the vicinity of the Burns temperature. It is shown that it is unlikely that the quasi-elastic scattering originates from the combined effects of coupling between TA and TO phonons with an increase of the damping of the TO phonon below T$_d$. The quasi-elastic scattering has a peak as a function of temperature close to the peak in the dielectric constant while the intensity of the central peak scattering increases strongly below this temperature. These results are discussed in terms of a random field model for relaxors

Soft Phonon Anomalies in the Relaxor Ferroelectric Pb(Zn_1/3Nb_2/3)_0.92Ti_0.08O_3

Neutron inelastic scattering measurements of the polar TO phonon mode dispersion in the cubic relaxor Pb(Zn_1/3Nb_2/3)_0.92Ti_0.08O_3 at 500K reveal anomalous behavior in which the optic branch appears to drop precipitously into the acoustic branch at a finite value of the momentum transfer q=0.2 inverse Angstroms, measured from the zone center. We speculate this behavior is the result of nanometer-sized polar regions in the crystal.Comment: 4 pages, 4 figure

A Neutron Elastic Diffuse Scattering Study of PMN

We have performed elastic diffuse neutron scattering studies on the relaxor Pb(Mg$_{1/3}$Nb$_{2/3}$)O$_3$ (PMN). The measured intensity distribution near a (100) Bragg peak in the (hk0) scattering plane assumes the shape of a butterfly with extended intensity in the (110) and (1$\bar{1}$0) directions. The temperature dependence of the diffuse scattering shows that both the size of the polar nanoregions (PNR) and the integrated diffuse intensity increase with cooling even for temperatures below the Curie temperature $T_C \sim 213$ K.Comment: Submitted to PR

Direct evidence of soft mode behavior near the Burns' temperature in PbMg1/3_{1 / 3}Nb2/3_{2 / 3}O3_{3} (PMN) relaxor ferroectric

Inelastic neutron scattering measurements of the relaxor ferroelectric PbMg$_{1 / 3}$Nb$_{2 / 3}$O$_{3}$ (PMN) in the temperature range 490~K$<$T$<$880~K directly observe the soft mode (SM) associated with the Curie-Weiss behavior of the dielectric constant $\varepsilon$(T). The results are treated within the framework of the coupled SM and transverse optic (TO1) mode and the temperature dependence of the SM frequency at q=0.075 a* is determined. The parameters of the SM are consistent with the earlier estimates and the frequency exhibits a minimum near the Burns temperature ($\approx$ 650K)Comment: 6 figure

Strong Influence of the diffuse component on the lattice dynamics in Pb(Mg1/3_{1/3}Nb2/3_{2/3})O3_{3}

The temperature and zone dependence of the lattice dynamics in Pb(Mg$_{1/3}$Nb$_{2/3}$)O$_{3}$ is characterized using neutron inelastic scattering. A strong correlation between the diffuse and phonon scattering is measured. The lattice dynamics in Brillouin zones where the diffuse scattering is strong is observed to display qualitatively different behavior than those zones where the diffuse scattering is weak. In the (220) and (200) zones, where there is a weak diffuse component, the dynamics are well described by coupled harmonic oscillators. Compared with SrTiO$_{3}$, the coupling is weak and isotropic, resulting in only a small transfer of spectral weight from one mode to another. A comparison of the scattering in these zones to the (110) zone, where a strong diffuse component is present, reveals a strong coupling of the diffuse (or central) component to the acoustic mode. We speculate that the coupling to the central peak is the reason for several recent conflicting interpretations of the lattice dynamics based on data from zones with a strong diffuse component.Comment: 7 pages, 7 figure

Proteomics of Human Dendritic Cell Subsets Reveals Subset-Specific Surface Markers and Differential Inflammasome Function.

Dendritic cells (DCs) play a key role in orchestrating adaptive immune responses. In human blood, three distinct subsets exist: plasmacytoid DCs (pDCs) and BDCA3+ and CD1c+ myeloid DCs. In addition, a DC-like CD16+ monocyte has been reported. Although RNA-expression profiles have been previously compared, protein expression data may provide a different picture. Here, we exploited label-free quantitative mass spectrometry to compare and identify differences in primary human DC subset proteins. Moreover, we integrated these proteomic data with existing mRNA data to derive robust cell-specific expression signatures with more than 400 differentially expressed proteins between subsets, forming a solid basis for investigation of subset-specific functions. We illustrated this by extracting subset identification markers and by demonstrating that pDCs lack caspase-1 and only express low levels of other inflammasome-related proteins. In accordance, pDCs were incapable of interleukin (IL)-1β secretion in response to ATP