Rapid and Robust Continuous Purification of High-Titer Hepatitis B Virus for In Vitro and In Vivo Applications

Available treatments for hepatitis B can control the virus but are rarely curative. This led to a global initiative to design new curative therapies for the 257 million patients affected. Discovery and development of these new therapies is contingent upon functional in vitro and in vivo hepatitis B virus (HBV) infection models. However, low titer and impurity of conventional HBV stocks reduce significance of in vitro infections and moreover limit challenge doses in current in vivo models. Therefore, there is a critical need for a robust, simple and reproducible protocol to generate high-purity and high-titer infectious HBV stocks. Here, we outline a three-step protocol for continuous production of high-quality HBV stocks from supernatants of HBV-replicating cell lines. This purification process takes less than 6 h, yields to high-titer stocks (up to 1 × 1011 enveloped, DNA-containing HBV particles/mL each week), and is with minimal equipment easily adaptable to most laboratory settings.Peer Reviewe

The build-up of the colour-magnitude relation in galaxy clusters since z~0.8

Using galaxy clusters from the ESO Distant Cluster Survey, we study how the distribution of galaxies along the colour-magnitude relation has evolved since z~0.8. While red-sequence galaxies in all these clusters are well described by an old, passively evolving population, we confirm our previous finding of a significant evolution in their luminosity distribution as a function of redshift. When compared to galaxy clusters in the local Universe, the high redshift EDisCS clusters exhibit a significant "deficit" of faint red galaxies. Combining clusters in three different redshift bins, and defining as `faint' all galaxies in the range 0.4 > L/L* > 0.1, we find a clear decrease in the luminous-to-faint ratio of red galaxies from z~0.8 to z~0.4. The amount of such a decrease appears to be in qualitative agreement with predictions of a model where the blue bright galaxies that populate the colour-magnitude diagram of high redshift clusters, have their star formation suppressed by the hostile cluster environment. Although model results need to be interpreted with caution, our findings clearly indicate that the red-sequence population of high-redshift clusters does not contain all progenitors of nearby red-sequence cluster galaxies. A significant fraction of these must have moved onto the red-sequence below z~0.8.Comment: 15 pages, 10 figures, accepted for publication in MNRA

The Grism lens-amplified survey from space (GLASS). VIII. The influence of the cluster properties on Halpha emitter galaxies at 0.3<z<0.7

Exploiting the data of the Grism Lens-Amplified Survey from Space (GLASS), we characterize the spatial distribution of star formation in 76 high star forming galaxies in 10 clusters at 0.3< z <0.7. All these galaxies are likely restricted to first infall. In a companion paper we contrast the properties of field and cluster galaxies, whereas here we correlate the properties of H{\alpha} emitters to a number of tracers of the cluster environment to investigate its role in driving galaxy transformations. H{\alpha} emitters are found in the clusters out to 0.5 virial radii, the maximum radius covered by GLASS. The peak of the H{\alpha} emission is offset with respect to the peak of the UV-continuum. We decompose this offsets into a radial and tangential component. The radial compo- nent points away from the cluster center in 60% of the cases, with 95% confidence. The decompositions agree with cosmological simulations, i.e. the H{\alpha} emission offset correlates with galaxy velocity and ram-pressure stripping signatures. Trends between H{\alpha} emitter properties and surface mass density distributions and X-ray emissions emerge only for unrelaxed clusters. The lack of strong correlations with the global environment does not allow us to identify a unique environmental effect originating from the cluster center. In contrast, correla- tions between H{\alpha} morphology and local number density emerge. We conclude that local effects, uncorrelated to the cluster-centric radius, play a more important role in shaping galaxy properties.Comment: ApJ in press (16 pages, 8 figures

The Grism Lens-Amplified Survey from Space (GLASS). V. Extent and spatial distribution of star formation in z~0.5 cluster galaxies

We present the first study of the spatial distribution of star formation in z~0.5 cluster galaxies. The analysis is based on data taken with the Wide Field Camera 3 as part of the Grism Lens-Amplified Survey from Space (GLASS). We illustrate the methodology by focusing on two clusters (MACS0717.5+3745 and MACS1423.8+2404) with different morphologies (one relaxed and one merging) and use foreground and background galaxies as field control sample. The cluster+field sample consists of 42 galaxies with stellar masses in the range 10^8-10^11 M_sun, and star formation rates in the range 1-20 M_sun/yr. Both in clusters and in the field, H{\alpha} is more extended than the rest-frame UV continuum in 60% of the cases, consistent with diffuse star formation and inside out growth. In ~20% of the cases, the H{\alpha} emission appears more extended in cluster galaxies than in the field, pointing perhaps to ionized gas being stripped and/or star formation being enhanced at large radii. The peak of the H{\alpha} emission and that of the continuum are offset by less than 1 kpc. We investigate trends with the hot gas density as traced by the X-ray emission, and with the surface mass density as inferred from gravitational lens models and find no conclusive results. The diversity of morphologies and sizes observed in H_alpha illustrates the complexity of the environmental process that regulate star formation. Upcoming analysis of the full GLASS dataset will increase our sample size by almost an order of magnitude, verifying and strengthening the inference from this initial dataset.Comment: 18 pages, 15 figures, accepted for publication in Ap

Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation

Introduction The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth. Methods Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4+ cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4+ cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments. Results Peripheral blood was isolated from 266 patients without diabetes mellitus (n=182), with diabetes mellitus not treated with metformin (n=34), and with diabetes mellitus actively taking metformin (n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4+ fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1β, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-β. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics. Conclusion Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment

The relation between star formation, morphology and local density in high redshift clusters and groups

We investigate how the [OII] properties and the morphologies of galaxies in clusters and groups at z=0.4-0.8 depend on projected local galaxy density, and compare with the field at similar redshifts and clusters at low-z. In both nearby and distant clusters, higher-density regions contain proportionally fewer star-forming galaxies, and the average [OII] equivalent width of star-forming galaxies is independent of local density. However, in distant clusters the average current star formation rate (SFR) in star-forming galaxies seems to peak at densities ~15-40 galaxies Mpc^{-2}. At odds with low-z results, at high-z the relation between star-forming fraction and local density varies from high- to low-mass clusters. Overall, our results suggest that at high-z the current star formation (SF) activity in star-forming galaxies does not depend strongly on global or local environment, though the possible SFR peak seems at odds with this conclusion. We find that the cluster SFR normalized by cluster mass anticorrelates with mass and correlates with the star-forming fraction. These trends can be understood given a) that the average star-forming galaxy forms about 1 Msun/yr in all clusters; b) that the total number of galaxies scales with cluster mass and c) the dependence of star-forming fraction on cluster mass. We present the morphology-density (MD) relation for our z=0.4-0.8 clusters, and uncover that the decline of the spiral fraction with density is entirely driven by galaxies of types Sc or later. For galaxies of a given Hubble type, we see no evidence that SF properties depend on local environment. In contrast with recent findings at low-z, in our distant clusters the SF-density relation and the MD-relation are equivalent, suggesting that neither of the two is more fundamental than the other.(abr.)Comment: 21 pages, 14 figures, accepted for publication in Ap

The evolution of the density of galaxy clusters and groups: denser environments at higher redshifts

We show that, observationally, the projected local density distribution in high-z clusters is shifted towards higher values compared to clusters at lower redshift. To search for the origin of this evolution, we analyze a sample of haloes selected from the Millennium Simulation and populated using semi-analytic models, investigating the relation between observed projected density and physical 3D density, using densities computed from the 10 and 3 closest neighbours. Both observationally and in the simulations, we study the relation between number of cluster members and cluster mass, and number of members per unit of cluster mass. We find that the observed evolution of projected densities reflects a shift to higher values of the physical 3D density distribution. In turn, this must be related with the globally higher number of galaxies per unit of cluster volume N/V in the past. We show that the evolution of N/V is due to a combination of two effects: a) distant clusters were denser in dark matter (DM) simply because the DM density within R_{200} (~the cluster virial radius) is defined to be a fixed multiple of the critical density of the Universe, and b) the number of galaxies per unit of cluster DM mass is remarkably constant both with redshift and cluster mass if counting galaxies brighter than a passively evolving magnitude limit. Our results highlight that distant clusters were much denser environments than today's clusters, both in galaxy number and mass, and that the density conditions felt by galaxies in virialized systems do not depend on the system mass.Comment: accepted for publication in MNRA

The build-up of the colour-magnitude relation in galaxy clusters since z∼ 0.8

Using galaxy clusters from the ESO Distant Cluster Survey, we study how the distribution of galaxies along the colour-magnitude relation has evolved since z∼ 0.8. While red-sequence galaxies in all these clusters are well described by an old, passively evolving population, we confirm our previous finding of a significant evolution in their luminosity distribution as a function of redshift. When compared to galaxy clusters in the local Universe, the high-redshift EDisCS clusters exhibit a significant deficit of faint red galaxies. Combining clusters in three different redshift bins, and defining as ‘faint' all galaxies in the range 0.4 ≳L/L*≳ 0.1, we find a clear decrease in the luminous-to-faint ratio of red galaxies from z∼ 0.8 to ∼0.4. The amount of such a decrease appears to be in qualitative agreement with predictions of a model where the blue bright galaxies that populate the colour-magnitude diagram of high-redshift clusters, have their star formation suppressed by the hostile cluster environment. Although model results need to be interpreted with caution, our findings clearly indicate that the red-sequence population of high-redshift clusters does not contain all progenitors of nearby red-sequence cluster galaxies. A significant fraction of these must have moved on to the red sequence below z∼ 0.

Galaxy stellar mass functions of different morphological types in clusters, and their evolution between z=0.8 and z=0

We present the galaxy stellar mass function (MF) and its evolution in clusters from z~0.8 to the current epoch, based on the WIde-field Nearby Galaxy-cluster Survey (WINGS) (0.04<z<0.07), and the ESO Distant Cluster Survey (EDisCS) (0.4<z <0.8). We investigate the total MF and find it evolves noticeably with redshift. The shape at M*>10^11 M' does not evolve, but below M*~10^10.8 M' the MF at high redshift is flat, while in the Local Universe it flattens out at lower masses. The population of M* = 10^10.2 - 10^10.8 M' galaxies must have grown significantly between z=0.8 and z=0. We analyze the MF of different morphological types (ellipticals, S0s and late-types), and find that also each of them evolves with redshift. All types have proportionally more massive galaxies at high- than at low-z, and the strongest evolution occurs among S0 galaxies. Examining the morphology-mass relation (the way the proportion of galaxies of different morphological types changes with galaxy mass), we find it strongly depends on redshift. At both redshifts, ~40% of the stellar mass is in elliptical galaxies. Another ~43% of the mass is in S0 galaxies in local clusters, while it is in spirals in distant clusters. To explain the observed trends, we discuss the importance of those mechanisms that could shape the MF. We conclude that mass growth due to star formation plays a crucial role in driving the evolution. It has to be accompanied by infall of galaxies onto clusters, and the mass distribution of infalling galaxies might be different from that of cluster galaxies. However, comparing with high-z field samples, we do not find conclusive evidence for such an environmental mass segregation. Our results suggest that star formation and infall change directly the MF of late-type galaxies in clusters and, indirectly, that of early-type galaxies through subsequent morphological transformations.Comment: MNRAS in press, 24 pages, 19 figures and 8 table

Artificial reefs built by 3D printing: systematisation in the design, material selection and fabrication

The recovery of degraded marine coasts and the improvement of natural habitats are current issues of vital importance for the development of life, both marine and terrestrial. In this sense, the immersion of artificial reefs (ARs) in the marine environment is a way to stimulate the recovery of these damaged ecosystems. But it is necessary to have a multidisciplinary approach that analyses the materials, designs and construction process of artificial reefs in order to understand their true impact on the environment. For this reason, this paper presents the manufacture of artificial reefs by 3D printing, proposing designs with a combination of prismatic and random shapes, with different external overhangs as well as inner holes. For the definition of the artificial reef designs, criteria provided by marine biologists and the results obtained from a numerical simulation with ANSYS were taken into account, with which the stability of the artificial reefs on the seabed was analysed. Three dosages of cement mortars and three dosages of geopolymer mortars were studied as impression materials. The studies included determination of the rheological properties of the mortars, to define the printability, determination of the cost of the materials used, and determination of the mechanical strength and biological receptivity in prismatic specimens that were immersed in the sea for 3 months. To evaluate the environmental impact of the materials used in the production of the mortars, a Life Cycle Assessment (LCA) was carried out. In order to choose the mortars that encompassed the best properties studied, Multi-Criteria Decision Making (MCDM) was applied and the two best mortars were used for the manufacture of the artificial reefs. Finally, the advantages and disadvantages of the 3D printing process used were analysed. The results of the studies carried out in this research show that cement mortars have better characteristics for artificial reef applications using 3D printing, and that the technique applied for the manufacture of the artificial reefs allowed the digital models to be faithfully reproduced.This work has been co-financed by the European Regional Development Fund through the Interreg Atlantic Area Programme, under the project “Artificial Reef 3D Printing for Atlantic Area - 3DPARE” (EAPA_174/2016). Besides, the authors want to thank the following companies for their contribution: Solvay, for supplying the fly ash and sodium hydroxide; BASF, for providing the additives used in the research; Abonomar S.L., for providing the seashells sand; FCC ámbito, for providing the crushed recycled glass and Grupo Cementos Portland Valderribas (Mataporquera plant) for providing the cement