Petrology, Mineral and Isotope Geochemistry of the External Liguride Peridotites (Northern Apennines, Italy)

Mantle peridotites of the External Liguride (EL) units (Northern Apennines) represent slices of subcontinental lithospheric mantle emplaced at the surface during early stages of rifting of the Jurassic Ligurian Piemontese basin. Petrological, ion probe and isotopic investigations have been used to unravel the nature of their mantle protolith and to constrain the timing and mechanisms of their evolution. EL peridotites are dominantly fertile spinel Iherzolites partly recrystallizfd in the plagiodase Iherzplite stability field Clinopyroxenes stable in the spinel-facies assemblage have nearly fiat REE patterns (CeN/SmN=0·6-0·8) at (10-16)×C1 and high Na, Sr, Ti and Zr contents. Kaersutitic-Ti-pargasitic amphiboles also occur in the spinel-facies assemblage. Their LREE-depleted REE spectra and very low Sr, Zr and Ba contents indicate that they crystallized from hydrous fluids with low concentrations of incompatible elements. Thermometric estimates on the spinelfacies parageneses yield lithospheric equilibrium temperatures in the range 1000-1100°C, in agreement with the stability of amphibole, which implies T<1100°C. Sr and Nd isotopic compositions, determined on carefully handpicked clinopyroxene separates, plot within the depleted end of the MORB field (87Sr/86Sr=0·70222-0·70263; 143Nd/144Nd=0·513047-0·513205) similar to many subcontinental orogenic spinel Iherzolites from the western Mediterranean area (e.g. Ivrea Zpne and Lanzfl N). The interpretation of the EL Iherzolites as subcontinental lithospheric mantle is reinforced by the occurrence of one extremely depleted isotopic composition (87Sr/86Sr=0·701736; 143Nd/144Nd=0·513543). Sr and Nd model ages, calculated assuming both CHUR and DM mantle sources, range between 2·4 Ga and 780 Ma. In particular, the 1·2-Ga Sr age and the 780-Ma Nd age can be regarded as minimum ages of differentiation. The transition from spinel-to plagioclase-facies assemblage, accompanied by progressive deformation (from granular to tectonite-mylonite textures), indicate that the EL Iherzolites experienced a later, subsolidus decompressional evolution, starting from subcontinental lithospheric levels. Sm/Nd isochrons on plagioclase-clinopyroxene pairs furnish ages of ∽165 Ma. This early Jurassic subsolidus decompressional history is consistent with uplift by means of denudation in response to passive and asymmetric lithospheric extension. This is considered to be the most suitable geodynamic mechanism to account for the exposure of huge bodies of subcontinental lithospheric mantle during early stages of opening of an oceanic basi

Pentraxin 3 in cardiovascular disease

The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The prototype of the pentraxin family is C reactive protein (CRP), a widely-used biomarker in human pathologies with an inflammatory or infectious origin. Data so far describe PTX3 as a multifunctional protein acting as a functional ancestor of antibodies and playing a regulatory role in inflammation. Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and inflammation is crucial in promoting it. Data from animal models indicate that PTX3 can have cardioprotective and atheroprotective roles regulating inflammation. PTX3 has been investigated in several clinical settings as possible biomarker of CVD. Data collected so far indicate that PTX3 plasma levels rise rapidly in acute myocardial infarction, heart failure and cardiac arrest, reflecting the extent of tissue damage and predicting the risk of mortality

Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium

Funding text The authors are grateful for the vital contributions of the participating study volunteers, clinicians, nurses, and laboratory technicians at the Surrey study site. The work by Roberto Leone, laboratory technician at Humanitas Clinical and Research Center, is gratefully acknowledged. Finally, they thank Ellen Oe (GSK) for scientific writing assistance. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115308, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. The contribution of the European Commission to the Advanced Immunization Technologies (ADITEC) project (grant agreement n° 280873) is also gratefully acknowledged. Publisher Copyright: © 2019, The Author(s).Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies. Healthy adults (N = 123; 20–21/group) received one immunization at Day (D)0. Alum-adjuvanted hepatitis B vaccine elicited vital signs and inflammatory (CRP/innate cells) responses that were similar between primed/naive vaccinees, and low-level gene responses. MF59-adjuvanted trivalent influenza vaccine (ATIV) induced distinct physiological (temperature/heart rate/reactogenicity) response-patterns not seen with non-adjuvanted TIV or with the other vaccines. ATIV also elicited robust early (D1) activation of IFN-related genes (associated with serum IP-10 levels) and innate-cell-related genes, and changes in monocyte/neutrophil/lymphocyte counts, while TIV elicited similar but lower responses. Due to viral replication kinetics, innate gene activation by live yellow-fever or varicella-zoster virus (YFV/VZV) vaccines was more suspended, with early IFN-associated responses in naïve YFV-vaccine recipients but not in primed VZV-vaccine recipients. Inflammatory responses (physiological/serum markers, innate-signaling transcripts) are therefore a function of the vaccine type/composition and presence/absence of immune memory. The data reported here have guided the design of confirmatory Phase IV trials using ATIV to provide tools to identify inflammatory or reactogenicity biomarkers.Peer reviewe

The World-Trade Web: Topological Properties, Dynamics, and Evolution

This paper studies the statistical properties of the web of import-export relationships among world countries using a weighted-network approach. We analyze how the distributions of the most important network statistics measuring connectivity, assortativity, clustering and centrality have co-evolved over time. We show that all node-statistic distributions and their correlation structure have remained surprisingly stable in the last 20 years -- and are likely to do so in the future. Conversely, the distribution of (positive) link weights is slowly moving from a log-normal density towards a power law. We also characterize the autoregressive properties of network-statistics dynamics. We find that network-statistics growth rates are well-proxied by fat-tailed densities like the Laplace or the asymmetric exponential-power. Finally, we find that all our results are reasonably robust to a few alternative, economically-meaningful, weighting schemes.Comment: 44 pages, 39 eps figure

The unintegrated gluon distribution from the CCFM equation

The gluon distribution f(x, k_t^2,mu^2), unintegrated over the transverse momentum k_t of the gluon, satisfies the angular-ordered CCFM equation which interlocks the dependence on the scale k_t with the scale \mu of the probe. We show how, to leading logarithmic accuracy, the equation can be simplified to a single scale problem. In particular we demonstrate how to determine the two-scale unintegrated distribution f(x,k_t^2,mu^2) from knowledge of the integrated gluon obtained from a unified scheme embodying both BFKL and DGLAP evolution.Comment: 16 pages LaTeX, 3 eps figure

Driver mutations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera

BACKGROUND: The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs. METHODS: We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations. RESULTS: PTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels. CONCLUSIONS: These results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed

Biophysical and Stabilization Studies of the Chlamydia trachomatis Mouse Pneumonitis Major Outer Membrane Protein

Native Chlamydia trachomatis mouse pneumonitis major outer membrane protein (nMOMP) induces effective protection against genital infection in a mouse challenge model. The conformation of nMOMP is crucial to confer this protective immunity. To achieve a better understanding of the conformational behavior and stability of nMOMP, a number of spectroscopic techniques are employed to characterize the secondary structure (circular dichroism), tertiary structure (intrinsic fluorescence) and aggregation properties (static light scattering and optical density) as a function of pH (3-8) and temperature (10-87.5°C). The data are summarized in an empirical phase diagram (EPD) which demonstrates that the thermal stability of nMOMP is strongly pH-dependent. Three distinctive regions are seen in the EPD. Below the major thermal transition regions, nMOMP remains in its native conformation over the pH range of 3-8. Above the thermal transitions, nMOMP appears in two different structurally altered states; one at pH 3-5 and the other at pH 6-8. The EPD shows that the highest thermal transition point (~ 65°C) of nMOMP is near pH 6. Several potential excipients such as arginine, sodium citrate, Brij 35, sucrose and guanidine are also selected to evaluate their effects on the stability of nMOMP. These particular compounds increase the aggregation onset temperature of nMOMP by more than 10°C, without affecting its secondary and tertiary structure. These results should help formulate a vaccine using a recombinant MOMP

More green and less blue water in the Alps during warmer summers

Climate change can reduce surface-water supply by enhancing evapotranspiration in forested mountains, especially during heatwaves. We investigate this ‘drought paradox’ for the European Alps using a 1,212-station database and hyper-resolution ecohydrological simulations to quantify blue (runoff) and green (evapotranspiration) water fluxes. During the 2003 heatwave, evapotranspiration in large areas over the Alps was above average despite low precipitation, amplifying the runoff deficit by 32% in the most runoff-productive areas (1,300–3,000 m above sea level). A 3 °C air temperature increase could enhance annual evapotranspiration by up to 100 mm (45 mm on average), which would reduce annual runoff at a rate similar to a 3% precipitation decrease. This suggests that green-water feedbacks—which are often poorly represented in large-scale model simulations—pose an additional threat to water resources, especially in dry summers. Despite uncertainty in the validation of the hyper-resolution ecohydrological modelling with observations, this approach permits more realistic predictions of mountain region water availability

Heavy Quark production at the TEVATRON and HERA using k_t-factorization with CCFM evolution

The application of k_t-factorization supplemented with the CCFM small-x evolution equation to heavy quark production at the TEVATRON and at HERA is discussed. The bb_bar production cross sections at the TEVATRON can be consistently described using the k_t-factorization formalism together with the unintegrated gluon density obtained within the CCFM evolution approach from a fit to HERA F_2 data. Special attention is drawn to the comparison with measured visible cross sections, which are compared to the hadron level Monte Carlo generator CASCADEComment: 13 pages, updated references and updated Fig. 9, Fig. 2 replace