Moving Mesh Cosmology: Properties of Gas Disks

We compare the structural properties of galaxies formed in cosmological simulations using the smoothed particle hydrodynamics (SPH) code GADGET with those using the moving-mesh code AREPO. Both codes employ identical gravity solvers and the same sub-resolution physics but use very different methods to track the hydrodynamic evolution of gas. This permits us to isolate the effects of the hydro solver on the formation and evolution of galactic gas disks in GADGET and AREPO haloes with comparable numerical resolution. In a matching sample of GADGET and AREPO haloes we fit simulated gas disks with exponential profiles. We find that the cold gas disks formed using the moving mesh approach have systematically larger disk scale lengths and higher specific angular momenta than their GADGET counterparts across a wide range in halo masses. For low mass galaxies differences between the properties of the simulated galaxy disks are caused by an insufficient number of resolution elements which lead to the artificial angular momentum transfer in our SPH calculation. We however find that galactic disks formed in massive halos, resolved with 10^6 particles/cells, are still systematically smaller in the GADGET run by a factor of ~2. The reasons for this are: 1) The excessive heating of haloes close to the cooling radius due to spurious dissipation of the subsonic turbulence in GADGET; and 2) The efficient delivery of low angular momentum gaseous blobs to the bottom of the potential well. While this large population of gaseous blobs in GADGET originates from the filaments which are pressure confined and fragment due to the SPH surface tension while infalling into hot halo atmospheres, it is essentially absent in the moving mesh calculation, clearly indicating numerical rather than physical origin of the blob material.Comment: 17 pages, 14 figures, MNRAS accepted. Movies and high-resolution images can be found at http://www.cfa.harvard.edu/itc/research/movingmeshcosmolog

Cellulolytic and proteolytic ability of bacteria isolated from gastrointestinal tract and composting of a hippopotamus

The bioprospection for cellulase and protease producers is a promise strategy for the discovery of potential biocatalysts for use in hydrolysis of lignocellulosic materials as well as proteic residues. These enzymes can increment and turn viable the production of second generation ethanol from different and alternative sources. In this context, the goal of this study was the investigation of cellulolytic and proteolytic abilities of bacteria isolated from the gastrointestinal tract of a hippopotamus as well as from its composting process. It is important to highlight that hippopotamus gastrointestinal samples were a non-typical sources of efficient hydrolytic bacteria with potential for application in biotechnological industries, like biofuel production. Looking for this, a total of 159 bacteria were isolated, which were submitted to qualitative and quantitative enzymatic assays. Proteolytic analyzes were conducted through the evaluation of fluorescent probes. Qualitative assays for cellulolytic abilities revealed 70 positive hits. After quantitative analyzes, 44 % of these positive hits were selected, but five (5) strains showed cellulolytic activity up to 11,8 FPU/mL. Regarding to proteolytic activities, six (6) strains showed activity above 10 %, which overpassed results described in the literature. Molecular analyzes based on the identification of 16S rDNA, revealed that all the selected bacterial isolates were affiliated to Bacillus genus. In summary, these results strongly indicate that the isolated bacteria from a hippopotamus can be a potential source of interesting biocatalysts with cellulolytic and proteolytic activities, with relevance for industrial applications.Brazilian research agency (FAPESP)Brazilian research agency (CAPES)Brazilian research agency (CNPq)Univ Fed Sao Paulo, Dept Biol Sci, Rua Sao Nicolau 210, BR-09913030 Sao Paulo, BrazilSao Paulo Zoo Pk Fdn, Av Miguel Estefano 4241, BR-04301905 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, Rua 3 Maio,100, BR-04044020 Sao Paulo, SP, BrazilFed Univ Latin Amer Integrat, Latin Amer Inst Life Sci & Nat, Av Tarquinio Joslin Santos 1000, BR-85870901 Foz Do Iguacu, Parana, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Rua Sao Nicolau 210, BR-09913030 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biophys, Rua 3 Maio,100, BR-04044020 Sao Paulo, SP, BrazilFAPESP: 2010/51992-5CNPq: 475166/2013-2Web of Scienc

Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer

Background: Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and -4 are highly expressed, but PAR-3 shows low expression and unclear functions. Methods: Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGF beta monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. Results: We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and -4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGF beta in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. Conclusions: Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells.Associacao Beneficente de Coleta de Sangue (Colsan)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Fed Sao Paulo, Dept Gynecol, BR-04024002 Sao Paulo, SP, BrazilCOLSAN, Charitable Assoc Blood Collect, BR-04080006 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biochem, BR-04024002 Sao Paulo, SP, BrazilAntonio Prudente Fdn, AC Camargo Canc Ctr, AC Camargo Hosp Biobank, Dept Pathol, BR-01509010 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Cellular Gynecol Lab, Dept Gynecol, Rua Napoleao Barros 608, BR-04024002 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Gynecol, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biochem, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Cellular Gynecol Lab, Dept Gynecol, Rua Napoleao Barros 608, BR-04024002 Sao Paulo, BrazilFAPESP: 2012/19780-3FAPESP: 2012/19851-8FAPESP: 2009/53766-5Web of Scienc

Moving mesh cosmology: the hydrodynamics of galaxy formation

We present a detailed comparison between the well-known SPH code GADGET and the new moving-mesh code AREPO on a number of hydrodynamical test problems. Through a variety of numerical experiments we establish a clear link between test problems and systematic numerical effects seen in cosmological simulations of galaxy formation. Our tests demonstrate deficiencies of the SPH method in several sectors. These accuracy problems not only manifest themselves in idealized hydrodynamical tests, but also propagate to more realistic simulation setups of galaxy formation, ultimately affecting gas properties in the full cosmological framework, as highlighted in papers by Vogelsberger et al. (2011) and Keres et al. (2011). We find that an inadequate treatment of fluid instabilities in GADGET suppresses entropy generation by mixing, underestimates vorticity generation in curved shocks and prevents efficient gas stripping from infalling substructures. In idealized tests of inside-out disk formation, the convergence rate of gas disk sizes is much slower in GADGET due to spurious angular momentum transport. In simulations where we follow the interaction between a forming central disk and orbiting substructures in a halo, the final disk morphology is strikingly different. In AREPO, gas from infalling substructures is readily depleted and incorporated into the host halo atmosphere, facilitating the formation of an extended central disk. Conversely, gaseous sub-clumps are more coherent in GADGET simulations, morphologically transforming the disk as they impact it. The numerical artefacts of the SPH solver are particularly severe for poorly resolved flows, and thus inevitably affect cosmological simulations due to their hierarchical nature. Our numerical experiments clearly demonstrate that AREPO delivers a physically more reliable solution.Comment: 32 pages, 27 figures, MNRAS accepted. Movies and high-resolution images can be found at http://www.cfa.harvard.edu/itc/research/movingmeshcosmology

Moving mesh cosmology: characteristics of galaxies and haloes

We discuss cosmological hydrodynamic simulations of galaxy formation performed with the new moving-mesh code AREPO, which promises higher accuracy compared with the traditional SPH technique that has been widely employed for this problem. We use an identical set of physics in corresponding simulations carried out with the well-tested SPH code GADGET, adopting also the same high-resolution gravity solver. We are thus able to compare both simulation sets on an object-by-object basis, allowing us to cleanly isolate the impact of different hydrodynamical methods on galaxy and halo properties. In accompanying papers, we focus on an analysis of the global baryonic statistics predicted by the simulation codes, (Vogelsberger et al. 2011) and complementary idealized simulations that highlight the differences between the hydrodynamical schemes (Sijacki et al. 2011). Here we investigate their influence on the baryonic properties of simulated galaxies and their surrounding haloes. We find that AREPO leads to significantly higher star formation rates for galaxies in massive haloes and to more extended gaseous disks in galaxies, which also feature a thinner and smoother morphology than their GADGET counterparts. Consequently, galaxies formed in AREPO have larger sizes and higher specific angular momentum than their SPH correspondents. The more efficient cooling flows in AREPO yield higher densities and lower entropies in halo centers (and the opposite trend in halo outskirts) leading to higher star formation rates of massive galaxies. While both codes agree to acceptable accuracy on a number of baryonic properties of cosmic structures, our results clearly demonstrate that galaxy formation simulations greatly benefit from the use of more accurate hydrodynamical techniques such as AREPO.Comment: 24 pages, 14 figures. MNRAS accepted (in press). Expanded introduction and discussion of galactic angular momentum; added references; one additional figure. Movies and high-resolution images can be found at http://www.cfa.harvard.edu/itc/research/movingmeshcosmology

Growing the first bright quasars in cosmological simulations of structure formation

We employ cosmological hydrodynamical simulations to study the growth of massive black holes (BHs) at high redshifts subject to BH merger recoils from gravitational wave emission. We select the most massive dark matter halo at z=6 from the Millennium simulation, and resimulate its formation at much higher resolution including gas physics and a model for BH seeding, growth and feedback. Assuming that the initial BH seeds are relatively massive, of the order of 10^5 Msun, and that seeding occurs around z~15 in dark matter haloes of mass 10^9-10^10 Msun, we find that it is possible to build up supermassive BHs (SMBHs) by z=6 that assemble most of their mass during extended Eddington-limited accretion periods. The properties of the simulated SMBHs are consistent with observations of z=6 quasars in terms of the estimated BH masses and bolometric luminosities, the amount of star formation occurring within the host halo, and the presence of highly enriched gas in the innermost regions of the host galaxy. After a peak in the BH accretion rate at z=6, the most massive BH has become sufficiently massive for the growth to enter into a much slower phase of feedback-regulated accretion. We explore the full range of expected recoils and radiative efficiencies, and also consider models with spinning BHs. In the most `pessimistic' case where BH spins are initially high, we find that the growth of the SMBHs can be potentially hampered if they grow mostly in isolation and experience only a small number of mergers. Whereas BH kicks can expel a substantial fraction of low mass BHs, they do not significantly affect the build up of the SMBHs. On the contrary, a large number of BH mergers has beneficial consequences for the growth of the SMBHs by considerably reducing their spin. [Abridged]Comment: 26 pages, 19 figures, minor revisions, MNRAS accepte

Analysis of catalytic properties of tripeptidyl peptidase I (TTP-I), a serine carboxyl lysosomal protease, and its detection in tissue extracts using selective FRET peptide substrate

Tripeptidyl peptidase I (TPP-I), also named ceroid lipofuscinosis 2 protease (CLN2p), is a serine carboxyl lysosomal protease involved in neurodegenerative diseases, and has both tripeptidyl amino- and endopeptidase activities under different pH conditions. We developed fluorescence resonance energy transfer (FRET) peptides using tryptophan (W) as the fluorophore to study TPP-I hydrolytic properties based on previous detailed substrate specificity study (Tian Y. et al., J. Biol. Chem. 2006, 281:6559-72). Tripeptidyl amino peptidase activity is enhanced by the presence of amino acids in the prime side and the peptide NH2-RWFFIQ-EDDnp is so far the best substrate described for TPP-I. The hydrolytic parameters of this peptide and its analogues indicated that the S-4 subsite of TPP-I is occluded and there is an electrostatic interaction of the positively charged substrate N-terminus amino group and a negative locus in the region of the enzyme active site. KCl activated TPP-I in contrast to the inhibition by Ca2+ and NaCl. Solvent kinetic isotope effects (SKIEs) show the importance of the free N-terminus amino group of the substrates, whose absence results in a more complex solvent-dependent enzyme: substrate interaction and catalytic process. Like pure TPP-I, rat spleen and kidney homogenates cleaved NH2-RWFFIQ-EDDnp only at F-F bond and is not inhibited by pepstatin, E-64, EDTA or PMSF. The selectivity of NH2-RWFFIQ-EDDnp to TPP-I was also demonstrated by the 400 times higher k(cat)/K-m compared to generally used substrate, NH2-AAF-MCA and by its resistance to hydrolysis by cathepsin D that is present in high levels in kidneys. (C) 2016 Elsevier Inc. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-Projects)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq-Projects)Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Rua Tres de Maio 100, BR-0404420 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, Rua Tres de Maio 100, BR-0404420 Sao Paulo, BrazilKyoto Inst Technol, Dept Appl Biol, Kyoto 606, JapanUniv Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Rua Tres de Maio 100, BR-0404420 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, Rua Tres de Maio 100, BR-0404420 Sao Paulo, BrazilFAPESP: 12/50191-4RFAPESP: 2013/12106-8CNPq: 471340/2011-1CNPq: 470388/2010-2Web of Scienc