Irreversible and reversible modes of operation of deterministic ratchets

We discuss a problem of optimization of the energetic efficiency of a simple rocked ratchet. We concentrate on a low-temperature case in which the particle's motion in a ratchet potential is deterministic. We show that the energetic efficiency of a ratchet working adiabatically is bounded from above by a value depending on the form of ratchet potential. The ratchets with strongly asymmetric potentials can achieve ideal efficiency of unity without approaching reversibility. On the other hand we show that for any form of the ratchet potential a set of time-protocols of the outer force exist under which the operation is reversible and the ideal value of efficiency is also achieved. The mode of operation of the ratchet is still quasistatic but not adiabatic. The high values of efficiency can be preserved even under elevated temperatures

Vacuum Choices and the Predictions of Inflation

In the presence of a short-distance cutoff, the choice of a vacuum state in an inflating, non-de Sitter universe is unavoidably ambiguous. The ambiguity is related to the time at which initial conditions for the mode functions are specified and to the way the expansion of the universe affects those initial conditions. In this paper we study the imprint of these uncertainties on the predictions of inflation. We parametrize the most general set of possible vacuum initial conditions by two phenomenological variables. We find that the generated power spectrum receives oscillatory corrections whose amplitude is proportional to the Hubble parameter over the cutoff scale. In order to further constrain the phenomenological parameters that characterize the vacuum definition, we study gravitational particle production during different cosmological epochs.Comment: 10 two-column pages, 1 figure; uses RevTeX

Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the <it>in vivo </it>imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield.</p> <p>Methods</p> <p>CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye. <it>In vivo </it>fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured.</p> <p>Results</p> <p>QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces.</p> <p>Conclusion</p> <p>Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was demonstrated. This work was done using very low doses of injected QDs and the detection was done using a minimally invasive method.</p

Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]International audienceInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly,chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR

Statefinder diagnostic and w−w′w-w^{\prime} analysis for interacting polytropic gas dark energy model

The interacting polytropic gas dark energy model is investigated from the viewpoint of statefinder diagnostic tool and $w-w^{\prime}$ analysis. The dependency of the statefinder parameters on the parameter of the model as well as the interaction parameter between dark matter and dark energy is calculated. We show that different values of the parameters of model and different values of interaction parameter result different evolutionary trajectories in $s-r$ and $w-w^{\prime}$ planes. The polytropic gas model of dark energy mimics the standard $\Lambda$CDM model at the early time.Comment: 17 pages, 4 figures, ijtp accepte

Adjustment for time-invariant and time-varying confounders in ‘unexplained residuals’ models for longitudinal data within a causal framework and associated challenges

‘Unexplained residuals’ models have been used within lifecourse epidemiology to model an exposure measured longitudinally at several time points in relation to a distal outcome. It has been claimed that these models have several advantages, including: the ability to estimate multiple total causal effects in a single model, and additional insight into the effect on the outcome of greater-than-expected increases in the exposure compared to traditional regression methods. We evaluate these properties and prove mathematically how adjustment for confounding variables must be made within this modelling framework. Importantly, we explicitly place unexplained residual models in a causal framework using directed acyclic graphs. This allows for theoretical justification of appropriate confounder adjustment and provides a framework for extending our results to more complex scenarios than those examined in this paper. We also discuss several interpretational issues relating to unexplained residual models within a causal framework. We argue that unexplained residual models offer no additional insights compared to traditional regression methods, and, in fact, are more challenging to implement; moreover, they artificially reduce estimated standard errors. Consequently, we conclude that unexplained residual models, if used, must be implemented with great care

Cell cycle-independent phospho-regulation of Fkh2 during hyphal growth regulates Candida albicans pathogenesis.

The opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Although previous gene-knockout studies have identified many factors involved in this transformation, it remains unclear how these factors are regulated to coordinate the switch. Investigating morphogenetic control by post-translational phosphorylation has generated important regulatory insights into this process, especially focusing on coordinated control by the cyclin-dependent kinase Cdc28. Here we have identified the Fkh2 transcription factor as a regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a role distinct from its conserved function in cell cycle progression. In stationary phase yeast cells 2D gel electrophoresis shows that there is a diverse pool of Fkh2 phospho-isoforms. For a short window on hyphal induction, far before START in the cell cycle, the phosphorylation profile is transformed before reverting to the yeast profile. This transformation does not occur when stationary phase cells are reinoculated into fresh medium supporting yeast growth. Mass spectrometry and mutational analyses identified residues phosphorylated by Cdc28 and Cbk1. Substitution of these residues with non-phosphorylatable alanine altered the yeast phosphorylation profile and abrogated the characteristic transformation to the hyphal profile. Transcript profiling of the phosphorylation site mutant revealed that the hyphal phosphorylation profile is required for the expression of genes involved in pathogenesis, host interaction and biofilm formation. We confirmed that these changes in gene expression resulted in corresponding defects in pathogenic processes. Furthermore, we identified that Fkh2 interacts with the chromatin modifier Pob3 in a phosphorylation-dependent manner, thereby providing a possible mechanism by which the phosphorylation of Fkh2 regulates its specificity. Thus, we have discovered a novel cell cycle-independent phospho-regulatory event that subverts a key component of the cell cycle machinery to a role in the switch from commensalism to pathogenicity