575 research outputs found
How high the temperature of a liquid be raised without boiling?
How high the temperature of a liquid be raised beyond its boiling point
without vaporizing (known as the limit of superheat) is an interesting subject
of investigation. A new method of finding the limit of superheat of liquids is
presented here. The superheated liquids are taken in the form of drops
suspended in visco elastic gel. The nucleation is detected acoustically by a
sensitive piezo-electric transducer, coupled to a multi channel scaler and the
nucleation is observed as a funtion of time and with increase of temperature.
The limit of superheat measured by the present method supersedes all other
measurements and theoretical predictions in reaching closest to the critical
temperature and warrants improved theoretical predictions.Comment: 10 pages, 1 fig. Phys, Rev. E. (2000) in pres
The air pressure effect on the homogeneous nucleation of carbon dioxide by molecular simulation
Vapour-liquid equilibria (VLE) and the influence of an inert carrier gas on
homogeneous vapour to liquid nucleation are investigated by molecular
simulation for quaternary mixtures of carbon dioxide, nitrogen, oxygen, and
argon. Canonical ensemble molecular dynamics simulation using the
Yasuoka-Matsumoto method is applied to nucleation in supersaturated vapours
that contain more carbon dioxide than in the saturated state at the dew line.
Established molecular models are employed that are known to accurately
reproduce the VLE of the pure fluids as well as their binary and ternary
mixtures. On the basis of these models, also the quaternary VLE properties of
the bulk fluid are determined with the Grand Equilibrium method.
Simulation results for the carrier gas influence on the nucleation rate are
compared with the classical nucleation theory (CNT) considering the "pressure
effect" [Phys. Rev. Lett. 101: 125703 (2008)]. It is found that the presence of
air as a carrier gas decreases the nucleation rate only slightly and, in
particular, to a significantly lower extent than predicted by CNT. The
nucleation rate of carbon dioxide is generally underestimated by CNT, leading
to a deviation between one and two orders of magnitude for pure carbon dioxide
in the vicinity of the spinodal line and up to three orders of magnitude in
presence of air as a carrier gas. Furthermore, CNT predicts a temperature
dependence of the nucleation rate in the spinodal limit, which cannot be
confirmed by molecular simulation
Superheated Microdrops as Cold Dark Matter Detectors
It is shown that under realistic background considerations, an improvement in
Cold Dark Matter sensitivity of several orders of magnitude is expected from a
detector based on superheated liquid droplets. Such devices are totally
insensitive to minimum ionizing radiation while responsive to nuclear recoils
of energies ~ few keV. They operate on the same principle as the bubble
chamber, but offer unattended, continuous, and safe operation at room
temperature and atmospheric pressure.Comment: 15 pgs, 4 figures include
Homogeneous Bubble Nucleation driven by local hot spots: a Molecular Dynamics Study
We report a Molecular Dynamics study of homogenous bubble nucleation in a
Lennard-Jones fluid. The rate of bubble nucleation is estimated using
forward-flux sampling (FFS). We find that cavitation starts with compact
bubbles rather than with ramified structures as had been suggested by Shen and
Debenedetti (J. Chem. Phys. 111:3581, 1999). Our estimate of the
bubble-nucleation rate is higher than predicted on the basis of Classical
Nucleation Theory (CNT). Our simulations show that local temperature
fluctuations correlate strongly with subsequent bubble formation - this
mechanism is not taken into account in CNT
CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN
SummaryTumor necrosis factor (TNF) induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD) in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS)-induced necroptosis was abrogated in Tnf−/− macrophages, a soluble TNF antagonist was not able to do so in Tnf+/+ macrophages, indicating that necroptosis occurs in a cell-autonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis-signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk
The de Rham homotopy theory and differential graded category
This paper is a generalization of arXiv:0810.0808. We develop the de Rham
homotopy theory of not necessarily nilpotent spaces, using closed dg-categories
and equivariant dg-algebras. We see these two algebraic objects correspond in a
certain way. We prove an equivalence between the homotopy category of schematic
homotopy types and a homotopy category of closed dg-categories. We give a
description of homotopy invariants of spaces in terms of minimal models. The
minimal model in this context behaves much like the Sullivan's minimal model.
We also provide some examples. We prove an equivalence between fiberwise
rationalizations and closed dg-categories with subsidiary data.Comment: 47 pages. final version. The final publication is available at
http://www.springerlink.co
Phagocytosis of Enterovirus-Infected Pancreatic β-Cells Triggers Innate Immune Responses in Human Dendritic Cells
Contains fulltext :
89763.pdf (publisher's version ) (Closed access)OBJECTIVE: Type 1 diabetes is a chronic endocrine disorder in which enteroviruses, such as coxsackie B viruses and echoviruses, are possible environmental factors that can trigger or accelerate disease. The development or acceleration of type 1 diabetes depends on the balance between autoreactive effector T-cells and regulatory T-cells. This balance is particularly influenced by dendritic cells (DCs). The goal of this study was to investigate the interaction between enterovirus-infected human pancreatic islets and human DCs. RESEARCH DESIGN AND METHODS: In vitro phagocytosis of human or porcine primary islets or Min6 mouse insuloma cells by DCs was investigated by flow cytometry and confocal analysis. Subsequent innate DC responses were monitored by quantitative PCR and Western blotting of interferon-stimulated genes (ISGs). RESULTS: In this study, we show that both mock- and coxsackievirus B3 (CVB3)-infected human and porcine pancreatic islets were efficiently phagocytosed by human monocyte-derived DCs. Phagocytosis of CVB3-infected, but not mock-infected, human and porcine islets resulted in induction of ISGs in DCs, including the retinoic acid-inducible gene (RIG)-I-like helicases (RLHs), RIG-I, and melanoma differentiation-associated gene 5 (Mda5). Studies with murine Min6 insuloma cells, which were also efficiently phagocytosed, revealed that increased ISG expression in DCs upon encountering CVB-infected cells resulted in an antiviral state that protected DCs from subsequent enterovirus infection. The observed innate antiviral responses depended on RNA within the phagocytosed cells, required endosomal acidification, and were type I interferon dependent. CONCLUSIONS: Human DCs can phagocytose enterovirus-infected pancreatic cells and subsequently induce innate antiviral responses, such as induction of RLHs. These responses may have important consequences for immune homeostasis in vivo and may play a role in the etiology of type 1 diabetes.1 mei 201
The Goldilocks Model for TCR—Too Much Attraction Might Not Be Best for Vaccine Design
Recent research on T cell-antigen interactions suggests that tighter binding is not always better at eliciting an effective immune response
Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation
Therapeutic vaccination with dendritic cells (DC) is an emerging investigational therapy for eradication of minimal residual disease in acute myeloid leukemia. Various strategies are being explored in manufacturing DC vaccines ex vivo, e.g., monocyte-derived DC (MoDC) loaded with leukemia-associated antigens (LAA). However, the optimal source of LAA and the choice of DC-activating stimuli are still not well defined. Here, loading with leukemic cell preparations (harboring both unknown and known LAA) was explored in combination with a DC maturation-inducing cytokine cocktail (CC; IL-1β, IL-6, TNF-α, and PGE2) and Toll-like receptor ligands (TLR-L) to optimize uptake. Since heat shock induced apoptotic blasts were more efficiently taken up than lysates, we focused on uptake of apoptotic leukemic cells. Uptake of apoptotic blast was further enhanced by the TLR7/8-L R848 (20–30%); in contrast, CC-induced maturation inhibited uptake. CC, and to a lesser extent R848, enhanced the ability of MoDC to migrate and stimulate T cells. Furthermore, class II-associated invariant chain peptide expression was down-modulated after R848- or CC-induced maturation, indicating enhanced processing and presentation of antigenic peptides. To improve both uptake and maturation, leukemic cells and MoDC were co-incubated with R848 for 24 h followed by addition of CC. However, this approach interfered with CC-mediated MoDC maturation as indicated by diminished migratory and T cell stimulatory capacity, and the absence of IL-12 production. Taken together, our data demonstrate that even though R848 improved uptake of apoptotic leukemic cells, the sequential use of R848 and CC is counter-indicated due to its adverse effects on MoDC maturation
To respond or not to respond - a personal perspective of intestinal tolerance
For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research
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