Thermodynamic Modeling of Fluid Polyamorphism in Hydrogen at Extreme Conditions

Fluid polyamorphism, the existence of multiple amorphous fluid states in a single-component system, has been observed or predicted in a variety of substances. A remarkable example of this phenomenon is the fluid-fluid phase transition in high-pressure hydrogen between insulating and conducting high-density fluids. This transition is induced by the reversible dimerization/dissociation of the molecular and atomistic states of hydrogen. In this work, we present the first attempt to thermodynamically model the fluid-fluid phase transition in hydrogen at extreme conditions. Our predictions for the phase coexistence and the reaction equilibrium of the two alternative forms of fluid hydrogen are based on experimental data and supported by the results of simulations. {Remarkably, we find that the law of corresponding states can be utilized to construct a unified equation of state combining the available computational results for different models of hydrogen and the experimental data.Comment: Manuscript intended for JC

Interfacial Properties of Fluids Exhibiting Liquid Polyamorphism and Water-Like Anomalies

It has been hypothesized that liquid polyamorphism, the existence of multiple amorphous states in a single component substance, may be caused by molecular or supramolecular interconversion. A simple microscopic model [Caupin and Anisimov, Phys. Rev. Lett., 127, 185701, (2021)] introduces interconversion in a compressible binary lattice to generate various thermodynamic scenarios for fluids that exhibit liquid polyamorphism and/or water-like anomalies. Using this model, we demonstrate the dramatic effects of interconversion on the interfacial properties. In particular, we find that the liquid-vapor surface tension exhibits either an inflection point or two extrema in its temperature dependence. Correspondingly, we observe anomalous behavior of the interfacial thickness and a significant shift in the location of the concentration profile with respect to the location of the density profile.Comment: This manuscript has been submitted to the Journal of Physical Chemistry B, as a part of the special issue, "Pablo G. Debenedetti Festschrift.

Molecular Targeting of Carbonic Anhydrase IX in Mice with Hypoxic HT29 Colorectal Tumor Xenografts

Background: Carbonic anhydrase IX (CAIX) is a membrane spanning protein involved in the enzymatic regulation of tumor acid-base balance. CAIX has been shown to be elevated in a number of hypoxic tumor types. The purpose of this study was to determine the efficiency of intact and IgG fragments of cG250 to target CAIX in vivo in a hypoxic tumor model. Methodology/Principal Findings: Conventional biodistribution studies were performed with 111 In-DO3A-cG250, 111 In-DO3A-F(ab’)2-cG250 and 111 In-DO3A-Fab-cG250. Additional ex vivo analysis of the tumor was performed with markers for tumor hypoxia, blood perfusion and endogenous CAIX expression. All four data sets were digitally correlated to determine the optimal agent for determining hypoxia in a HT29 colon cancer xenograft. The HT29 human colorectal tumor xenografts show strong CAIX expression in hypoxic areas of poor blood perfusion. The intact IgG had an initial high focal uptake at the periphery of these hypoxic regions and penetration into the areas of highest CAIX expression over the 7-day study period. The lower molecular weight antibody fragments had a faster uptake into areas of high CAIX expression, but had a much lower absolute uptake at the optimal imaging times. Conclusions/Significance: For the clinical detection of hypoxia induced CAIX using cG250 antibody based agents, imagin

Unknown Primary Melanoma: Worldwide Survey on Clinical Management

Background: How to deal with melanoma of unknown primary (MUP) origin is a debated topic in the literature. Objective: We performed a worldwide survey to inquire what clinical and investigational workup is performed as well as the physicians' perception of this disease. Methods: A questionnaire was sent via mail to clinicians involved in melanoma care from December 2015 to April 2016 using the International Dermoscopy Society website. Results: 119 physicians from 47 different countries answered the questionnaire. The most reported examination was skin examination followed by CT and/or PET scans. All the participants declared asking about previous excisions of skin lesions with 81% of them asking for a histopathological slide review of previous biopsies. Half of the participants checked for a possible vitiligo phenomenon that may explain regression of the primary lesion. BRAF, cKIT, and GNAQ mutations were screened by 32% of participants. The majority of participants (76%) applied the same treatment protocols for MUP as patients with known primary melanomas of the same AJCC stage. Conclusion: Strong heterogeneity was found between physicians dealing with MUP. Thus, a consensus document should be strongly encouraged

A structure in the early Universe at z 1.3 that exceeds the homogeneity scale of the R-W concordance cosmology

A Large Quasar Group (LQG) of particularly large size and high membership has been identified in the DR7QSO catalogue of the Sloan Digital Sky Survey. It has characteristic size (volume^1/3) ~ 500 Mpc (proper size, present epoch), longest dimension ~ 1240 Mpc, membership of 73 quasars, and mean redshift = 1.27. In terms of both size and membership it is the most extreme LQG found in the DR7QSO catalogue for the redshift range 1.0 = 1.28, which is itself one of the more extreme examples. Their boundaries approach to within ~ 2 deg (~ 140 Mpc projected). This new, huge LQG appears to be the largest structure currently known in the early universe. Its size suggests incompatibility with the Yadav et al. scale of homogeneity for the concordance cosmology, and thus challenges the assumption of the cosmological principle

Crambescin C1 Acts as A Possible Substrate of iNOS and eNOS Increasing Nitric Oxide Production and Inducing In Vivo Hypotensive Effect

Crambescins are guanidine alkaloids from the sponge Crambe crambe. Crambescin C1 (CC) induces metallothionein genes and nitric oxide (NO) is one of the triggers. We studied and compared the in vitro, in vivo, and in silico effects of some crambescine A and C analogs. HepG2 gene expression was analyzed using microarrays. Vasodilation was studied in rat aortic rings. In vivo hypotensive effect was directly measured in anesthetized rats. The targets of crambescines were studied in silico. CC and homo-crambescine C1 (HCC), but not crambescine A1 (CA), induced metallothioneins transcripts. CC increased NO production in HepG2 cells. In isolated rat aortic rings, CC and HCC induced an endothelium-dependent relaxation related to eNOS activation and an endothelium-independent relaxation related to iNOS activation, hence both compounds increase NO and reduce vascular tone. In silico analysis also points to eNOS and iNOS as targets of Crambescin C1 and source of NO increment. CC effect is mediated through crambescin binding to the active site of eNOS and iNOS. CC docking studies in iNOS and eNOS active site revealed hydrogen bonding of the hydroxylated chain with residues Glu377 and Glu361, involved in the substrate recognition, and explains its higher binding affinity than CA. The later interaction and the extra polar contacts with its pyrimidine moiety, absent in the endogenous substrate, explain its role as exogenous substrate of NOSs and NO production. Our results suggest that CC serve as a basis to develop new useful drugs when bioavailability of NO is perturbed.Fil: Rubiolo, Juan Andrés. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Ministerio de Ciencia, Tecnologia E Innovacion Productiva (santa Fe). - Gobierno de la Provincia de Santa Fe. Ministerio de Ciencia, Tecnologia E Innovacion Productiva (santa Fe).; Argentina. Universidad de Santiago de Compostela; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Lence, Emilio. Universidad de Santiago de Compostela; EspañaFil: González Bello, Concepción. Universidad de Santiago de Compostela; EspañaFil: Roel, María. Universidad de Santiago de Compostela; EspañaFil: Gil Longo, José. Universidad de Santiago de Compostela; EspañaFil: Campos Toimil, Manuel. Universidad de Santiago de Compostela; EspañaFil: Ternon, Eva. Université Nice Sophia Antipolis. Laboratoire Jean-alexandre Dieudonné.; FranciaFil: Thomas, Olivier P.. National University of Ireland Galway; IrlandaFil: González Cantalapiedra, Antonio. Universidad de Santiago de Compostela; EspañaFil: López Alonso, Henar. Universidad de Santiago de Compostela; EspañaFil: Vieytes, Mercedes R.. Universidad de Santiago de Compostela; EspañaFil: Botana, Luis M.. Universidad de Santiago de Compostela; Españ

Observation of Pulsed Gamma-rays Above 25 GeV from the Crab Pulsar with MAGIC

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 GeV. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 GeV, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.Comment: Slight modification of the analysis: Fitting a more general function to the combined data set of COMPTEL, EGRET and MAGIC. Final result and conclusion is unchange

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)

Search for Branons at LEP

We search, in the context of extra-dimension scenarios, for the possible existence of brane fluctuations, called branons. Events with a single photon or a single Z-boson and missing energy and momentum collected with the L3 detector in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are analysed. No excess over the Standard Model expectations is found and a lower limit at 95% confidence level of 103 GeV is derived for the mass of branons, for a scenario with small brane tensions. Alternatively, under the assumption of a light branon, brane tensions below 180 GeV are excluded