The Glass Transition Temperature of Water: A Simulation Study

We report a computer simulation study of the glass transition for water. To mimic the difference between standard and hyperquenched glass, we generate glassy configurations with different cooling rates and calculate the $T$ dependence of the specific heat on heating. The absence of crystallization phenomena allows us, for properly annealed samples, to detect in the specific heat the simultaneous presence of a weak pre-peak (``shadow transition''), and an intense glass transition peak at higher temperature. We discuss the implications for the currently debated value of the glass transition temperature of water. We also compare our simulation results with the Tool-Narayanaswamy-Moynihan phenomenological model.Comment: submitted to Phys. Re

Interaction of acridine-calix[4]arene with DNA at the electrified liquid|liquid interface

The behaviour of an acridine-functionalised calix[4]arene at the interface between two immiscible electrolyte solutions (ITIES) is reported. Molecular modelling showed that the acridine-calix[4]arene has regions of significant net positive charge spread throughout the protonated acridine moieties, consistent with it being able to function as an anion ionophore. The presence of this compound in the organic phase facilitated the transfer of aqueous phase electrolyte ions. Upon addition of double stranded DNA to the aqueous phase, the transfer of electrolyte anions was diminished, due to DNA binding to the acridine moiety at the ITIES. The behaviour provides a basis for DNA hybridization detection using electrochemistry at the ITIES

Origin of non-exponential relaxation in a crystalline ionic conductor: a multi-dimensional 109Ag NMR study

The origin of the non-exponential relaxation of silver ions in the crystalline ion conductor Ag7P3S11 is analyzed by comparing appropriate two-time and three-time 109Ag NMR correlation functions. The non-exponentiality is due to a rate distribution, i.e., dynamic heterogeneities, rather than to an intrinsic non-exponentiality. Thus, the data give no evidence for the relevance of correlated back-and-forth jumps on the timescale of the silver relaxation.Comment: 4 pages, 3 figure

Solidity of Viscous Liquids

Recent NMR experiments on supercooled toluene and glycerol by Hinze and Bohmer show that small rotation angles dominate with only few large molecular rotations. These results are here interpreted by assuming that viscous liquids are solid-like on short length scales. A characteristic length, the "solidity length", separates solid-like behavior from liquid-like behavior.Comment: Plain RevTex file, no figure

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8[superscript +] T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4[superscript +] T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.Bill & Melinda Gates FoundationRagon Institute of MGH, MIT and HarvardNational Institutes of Health (U.S.) (AI091693)National Institutes of Health (U.S.) (AI095109)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32CA180586)Hertz Foundation (Graduate Fellowship)National Science Foundation (U.S.). Graduate Research Fellowshi

Dielectric and conductivity relaxation in mixtures of glycerol with LiCl

We report a thorough dielectric characterization of the alpha relaxation of glass forming glycerol with varying additions of LiCl. Nine salt concentrations from 0.1 - 20 mol% are investigated in a frequency range of 20 Hz - 3 GHz and analyzed in the dielectric loss and modulus representation. Information on the dc conductivity, the dielectric relaxation time (from the loss) and the conductivity relaxation time (from the modulus) is provided. Overall, with increasing ion concentration, a transition from reorientationally to translationally dominated behavior is observed and the translational ion dynamics and the dipolar reorientational dynamics become successively coupled. This gives rise to the prospect that by adding ions to dipolar glass formers, dielectric spectroscopy may directly couple to the translational degrees of freedom determining the glass transition, even in frequency regimes where usually strong decoupling is observed.Comment: 8 pages, 7 figure

NQO2 is a reactive oxygen species generating off-target for acetaminophen

[Image: see text] The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity

Glassy Phase Transition and Stability in Black Holes

Black hole thermodynamics, confined to the semi-classical regime, cannot address the thermodynamic stability of a black hole in flat space. Here we show that inclusion of correction beyond the semi-classical approximation makes a black hole thermodynamically stable. This stability is reached through a phase transition. By using Ehrenfest's scheme we further prove that this is a glassy phase transition with a Prigogine-Defay ratio close to 3. This value is well placed within the desired bound (2 to 5) for a glassy phase transition. Thus our analysis indicates a very close connection between the phase transition phenomena of a black hole and glass forming systems. Finally, we discuss the robustness of our results by considering different normalisations for the correction term.Comment: v3, minor changes over v2, references added, LaTeX-2e, 18 pages, 3 ps figures, to appear in Eour. Phys. Jour.