Inverse cascades sustained by the transfer rate of angular momentum in a 3D turbulent flow

The existence of energy cascades as signatures of conserved magnitudes is one of the universal characteristics of turbulent flows. In homogeneous 3D turbulence, the energy conservation produces a direct cascade from large to small scales, although in 2D, it produces an inverse cascade pointing towards small wave numbers. In this Letter, we present the first evidence of an inverse cascade in a fully developed 3D experimental turbulent flow where the conserved magnitude is the angular momentum. Two counterrotating flows collide in a central region where very large fluctuations are produced, generating a turbulent drag that transfers the external torque between different fluid layers

Cosmic ray energy changes at the termination shock and in the heliosheath

Voyager 1 crossed the termination shock of the solar wind in December 2004 at 94 AU and currently measures the cosmic ray intensity in the heliosheath. To better understand this modulation region beyond the shock, where adiabatic energy changes should be small, we review the net effect of energy changes during the modulation process, including adiabatic deceleration in the solar wind, acceleration at the termination shock, and the possibility that stochastic acceleration in the heliosheath may also make a contribution

Interleukin-1 receptor antagonist mediates toll-like receptor 3-induced inhibition of trophoblast adhesion to endometrial cells in vitro

STUDY QUESTION Is interleukin-1 receptor antagonist (IL-1RA) involved in the toll-like receptor 3 (TLR 3)-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro? SUMMARY ANSWER IL-1RA mediates the TLR 3-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro. WHAT IS KNOWN ALREADY It is well documented that endometrial TLR 3 activation leads to impairment of trophoblast binding to endometrial cells in vitro. IL-1RA is known as an anti-implantation factor, as its injection significantly reduced implantation rates in mice by an effect on endometrial receptivity. STUDY DESIGN, SIZE, DURATION Poly I:C was used as a TLR3 specific ligand and endometrial cells were either treated or not with Poly I:C (treated versus control) in vitro. IL-1RA was applied to block IL-1 signal transduction. IL-1RA was knocked down by Accell Human IL1RN siRNA. Flagellin was used to stimulate TLR 5. SP600125 (JNK) was applied to inhibit the mitogen-activated protein kinases (MAPK) pathway. BAY11 -7082 was used to inhibit the nuclear factor-κB (NF-κB) pathway. The experiments were performed in three replicates on three separate days. PARTICIPANTS/MATERIALS, SETTING, METHODS An in vitro assay was developed using RL95-2 (an endometrial cell line) and JAr (a trophoblast cell line) cells. Initially, the production of IL-1RA in RL95-2 cells in response to TLR 3 activation was measured. To determine whether the TLR 3-induced inhibition of trophoblast binding was mediated through IL-1RA: (i) we evaluated the effect of IL-1RA on the attachment of trophoblast cells to endometrial cells; (ii) we knocked down TLR3-induced IL-1RA gene expression by IL-1RA Small interfering RNA (siRNA) and evaluated trophoblast attachment to endometrial cells. Finally, to clarify through which pathway TLR 3-induced inhibition of trophoblast binding occurs: (i) activation of NF-κB and MAPK was detected by transfecting the cells with secreted placental alkaline phosphatase reporter plasmids bearing promoter sequences for each transcription factor; (ii) the inhibitors for NF-κB and MAPK were used to block signaling; (iii) it was then investigated whether addition of these inhibitors could restore the TLR 3-induced impairment of trophoblast attachment to the endometrial cells. MAIN RESULTS AND THE ROLE OF CHANCE Our results showed that addition of polyinosinic:polycytidylic acid (Poly I:C) to RL95-2 cells significantly increased the production of IL-1RA (P < 0.05). Addition of human recombinant IL-1RA to RL95-2 cells remarkably decreased the adhesion rate of trophoblast cells to endometrial cells (P < 0.05). In addition, suppression of TLR3-induced IL-1RA gene expression in RL95-2 cells significantly restored trophoblast cells attachment to endometrial cells in the presence of Poly I:C (P < 0.05). Only TLR3 and not TLR5 induced MAPK activation (P < 0.05). TLR3 ligation did not affect NF-κB activation. Of NF-kB and MAPK inhibitors, only MAPK's inhibitor could achieve restoration of spheroid adhesion to endometrial cells (P < 0.05). LIMITATIONS, REASONS FOR CAUTION This study has been only done in vitro. Future in vivo studies will confirm our data. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study have a potential clinical application in introducing IL-1RA as one of the diagnostic infertility markers in the endometrium, which can affect the process of embryo adhesion at the time of implantation. Moreover, based on the novel data obtained in the current study, blocking and regulating the MAPK pathway by its inhibitors can be used as a new strategy to prevent and treat virus-induced infertility cases in ART techniques. STUDY FUNDING/COMPETING INTEREST This study was partially funded by a Marie Curie IIF-253948 grant to I.C. and was partially funded by the author's institutions. The authors have no conflict of interest to declare

Depletion of chlorine into HCl ice in a protostellar core

The freezeout of gas-phase species onto cold dust grains can drastically alter the chemistry and the heating-cooling balance of protostellar material. In contrast to well-known species such as carbon monoxide (CO), the freezeout of various carriers of elements with abundances $<10^{-5}$ has not yet been well studied. Our aim here is to study the depletion of chlorine in the protostellar core, OMC-2 FIR 4. We observed transitions of HCl and H2Cl+ towards OMC-2 FIR 4 using the Herschel Space Observatory and Caltech Submillimeter Observatory facilities. Our analysis makes use of state of the art chlorine gas-grain chemical models and newly calculated HCl-H$_{2}$ hyperfine collisional excitation rate coefficients. A narrow emission component in the HCl lines traces the extended envelope, and a broad one traces a more compact central region. The gas-phase HCl abundance in FIR 4 is 9e-11, a factor of only 0.001 that of volatile elemental chlorine. The H2Cl+ lines are detected in absorption and trace a tenuous foreground cloud, where we find no depletion of volatile chlorine. Gas-phase HCl is the tip of the chlorine iceberg in protostellar cores. Using a gas-grain chemical model, we show that the hydrogenation of atomic chlorine on grain surfaces in the dark cloud stage sequesters at least 90% of the volatile chlorine into HCl ice, where it remains in the protostellar stage. About 10% of chlorine is in gaseous atomic form. Gas-phase HCl is a minor, but diagnostically key reservoir, with an abundance of <1e-10 in most of the protostellar core. We find the 35Cl/37Cl ratio in OMC-2 FIR 4 to be 3.2\pm0.1, consistent with the solar system value.Comment: 13 pages, 12 figures, accepted for publication in A&

Cosmic-ray energy changes in the heliosphere. II. The effect on K-capture electron secondaries

Recent accurate measurements of the cosmic-ray intensity ratio ^(51)V/^(51)Cr below 1 GeV nucleon^(-1) provide a powerful new tool to study cosmic-ray modulation in the heliosphere. This paper describes how energy changes during this modulation process influence this ratio. In particular, our model includes acceleration at the solar wind termination shock, and we find that this mechanism significantly enhances the ^(51)V/^(51)Cr ratio at 1 AU. It is also shown that this acceleration makes the ratio more sensitive to the form of local low-energy interstellar spectra, below ~100 MeV nucleon^(-1), than without it. Specifically, this acceleration provides an independent confirmation of the consensus that low-energy spectra should be flatter than their high-energy power-law forms

The FXII c.-4T > C Polymorphism as a Disease Modifier in Patients With Hereditary Angioedema Due to the FXII p.Thr328Lys Variant

Background: Hereditary angioedema due to the Thr328Lys variant in the coagulation factor XII (HAE-FXII) affects mainly women in whom the symptomatology is dependent on high estrogen levels. Clinical variability and incomplete penetrance are challenging features that hinder the diagnosis and management of HAE-FXII. The c.-4T>C Kozak polymorphism is the only common variation accounting for FXII plasma levels and was previously shown to modify the course of HAE due to C1-Inhibitor deficiency. Objectives: To assess the influence of the c.-4T>C polymorphism on disease expression in 39 Spanish HAE-FXII index patients. Methods: The c.-4T>C polymorphism was sequenced by the standard Sanger method, and HAE severity was calculated according to the score by Cumming et al. (2003) The activation of the contact system was quantified by the kallikrein-like activity of plasma in chromogenic assays upon activation with high-molecular-weight dextran sulfate. Results: The c.-4CC genotype was overrepresented in the studied cohort: 82% were CC-homozygous (expected frequency = 59%) and 18% were CT-heterozygous (expected frequency = 39%) (p = 0.001). Patients with a c.-4CC genotype exhibited higher kallikrein-like activity (0.9659 +/- 0.1136) than those with a c.-4TC genotype (0.7645 +/- 0.1235) (p = 0.024) or healthy donors. Moreover, the polymorphism influenced HAE-FXII severity score (c.-4CC = 4.43 +/- 2.28 vs c.-4TC = 2.0 +/- 1.15; p = 0.006) but not the degree of estrogen dependence or time until remission. Conclusion: The c.-4T>C polymorphism is overrepresented in a Spanish HAE-FXII cohort and significantly influences the degree of contact system activation and the clinical severity of the disease

Human Trophoblast Cells Modulate Endometrial Cells Nuclear Factor kappa B Response to Flagellin In Vitro

Background: Implantation is a complex process that requires a delicate cooperation between the immune and reproductive system. Any interference in the fine balance could result in embryo loss and infertility. We have recently shown that Toll-like receptor 5 activation results in a decrease of trophoblast cells binding to endometrial cells in an in vitro model of human implantation. However, little is known about the downstream signalling leading to the observed failure in implantation and the factors that modulate this immune response. Methods and Principal Findings: An in vitro model of embryo implantation was used to evaluate the effect of trophoblasts and flagellin on the activation of NF-kappa B in endometrial cells and whether TLR5-related in vitro implantation failure is signalled through NF-kappa B. We generated two different NF-kappa B reporting cell lines by transfecting either an immortalized endometrial epithelial cell line (hTERT-EECs) or a human endometrial carcinoma cell line (Ishikawa 3-H-12) with a plasmid containing the secreted alkaline phosphatase (SEAP) under the control of five NF-kappa B sites. The presence of trophoblast cells as well as flagellin increased NF-kappa B activity when compared to controls. The NF-kappa B activation induced by flagellin was further increased by the addition of trophoblast cells. Moreover, blocking NF-kappa B signalling with a specific inhibitor (BAY11-7082) was able to restore the binding ability of our trophoblast cell line to the endometrial monolayer. Conclusions: These are the first results showing a local effect of the trophoblasts on the innate immune response of the endometrial epithelium. Moreover, we show that implantation failure caused by intrauterine infections could be associated with abnormal levels of NF-kappa B activation. Further studies are needed to evaluate the target genes through which NF-kappa B activation after TLR5 stimulation lead to failure in implantation and the effect of the embryo on those genes. Understanding these pathways could help in the diagnosis and treatment of implantation failure cases

Stability and Reversible Oxidation of Sub-Nanometric Cu5 Metal Clusters: Integrated Experimental Study and Theoretical Modeling**

Sub-nanometer metal clusters have special physical and chemical properties, significantly different from those of nanoparticles. However, there is a major concern about their thermal stability and susceptibility to oxidation. In situ X-ray Absorption spectroscopy and Near Ambient Pressure X-ray Photoelectron spectroscopy results reveal that supported Cu5 clusters are resistant to irreversible oxidation at least up to 773 K, even in the presence of 0.15 mbar of oxygen. These experimental findings can be formally described by a theoretical model which combines dispersion-corrected DFT and first principles thermochemistry revealing that most of the adsorbed O2 molecules are transformed into superoxo and peroxo species by an interplay of collective charge transfer within the network of Cu atoms and large amplitude “breathing” motions. A chemical phase diagram for Cu oxidation states of the Cu5-oxygen system is presented, clearly different from the already known bulk and nano-structured chemistry of Cu

Ribavirin as a First Treatment Approach for Hepatitis E Virus Infection in Transplant Recipient Patients

The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this situation, implementation of therapy is mandatory in the sense to facilitate viral clearance. Currently, there are no specific drugs approved for HEV infection, but ribavirin (RBV), the drug of choice, is used for off-label treatment. Here, we present two cases of chronic HEV infection in transplant patients, reviewing and discussing the therapeutic approach available in the literature. The use of RBV for the treatment of an HEV infection in organ transplant patients seems to be effective. The recommendation of 12 weeks of therapy is adequate in terms of efficacy. Nevertheless, there are important issues that urgently need to be assessed, such as optimal duration of therapy and drug dosage