Narrow-band search of continuous gravitational-wave signals from Crab and Vela pulsars in Virgo VSR4 data

In this paper we present the results of a coherent narrow-band search for continuous gravitational-wave signals from the Crab and Vela pulsars conducted on Virgo VSR4 data. In order to take into account a possible small mismatch between the gravitational-wave frequency and two times the star rotation frequency, inferred from measurement of the electromagnetic pulse rate, a range of 0.02 Hz around two times the star rotational frequency has been searched for both the pulsars. No evidence for a signal has been found and 95% confidence level upper limits have been computed assuming both that polarization parameters are completely unknown and that they are known with some uncertainty, as derived from x-ray observations of the pulsar wind torii. For Vela the upper limits are comparable to the spin-down limit, computed assuming that all the observed spin-down is due to the emission of gravitational waves. For Crab the upper limits are about a factor of 2 below the spin-down limit, and represent a significant improvement with respect to past analysis. This is the first time the spin-down limit is significantly overcome in a narrow-band search.

Directed search for gravitational waves from Scorpius X-1 with initial LIGO data

We present results of a search for continuously emitted gravitational radiation, directed at the brightest low-mass x-ray binary, Scorpius X-1. Our semicoherent analysis covers 10 days of LIGO S5 data ranging from 50-550 Hz, and performs an incoherent sum of coherent F-statistic power distributed amongst frequency-modulated orbital sidebands. All candidates not removed at the veto stage were found to be consistent with noise at a 1% false alarm rate. We present Bayesian 95% confidence upper limits on gravitational-wave strain amplitude using two different prior distributions: a standard one, with no a priori assumptions about the orientation of Scorpius X-1; and an angle-restricted one, using a prior derived from electromagnetic observations. Median strain upper limits of 1.3 x 10(-24) and 8 x 10(-25) are reported at 150 Hz for the standard and angle-restricted searches respectively. This proof-of-principle analysis was limited to a short observation time by unknown effects of accretion on the intrinsic spin frequency of the neutron star, but improves upon previous upper limits by factors of similar to 1.4 for the standard, and 2.3 for the angle-restricted search at the sensitive region of the detector.

Advanced LIGO

The Advanced LIGO gravitational wave detectors are second-generation instruments designed and built for the two LIGO observatories in Hanford, WA and Livingston, LA, USA. The two instruments are identical in design, and are specialized versions of a Michelson interferometer with 4 km long arms. As in Initial LIGO, Fabry-Perot cavities are used in the arms to increase the interaction time with a gravitational wave, and power recycling is used to increase the effective laser power. Signal recycling has been added in Advanced LIGO to improve the frequency response. In the most sensitive frequency region around 100 Hz, the design strain sensitivity is a factor of 10 better than Initial LIGO. In addition, the low frequency end of the sensitivity band is moved from 40 Hz down to 10 Hz. All interferometer components have been replaced with improved technologies to achieve this sensitivity gain. Much better seismic isolation and test mass suspensions are responsible for the gains at lower frequencies. Higher laser power, larger test masses and improved mirror coatings lead to the improved sensitivity at mid and high frequencies. Data collecting runs with these new instruments are planned to begin in mid-2015.

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pretreatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC

We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.

Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV

The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.

DNA barcoding taxonomy and diversity of the Mediterranean sharks and rays

Elasmobranchs are an important by-catch of commercial fisheries targeting bony fishes. Fisheries targeting sharks are rare, but usually almost all specimen bycatched are marketed. They risk extinction if current fishing pressure continues (Ferretti et al., 2008). Accurate species identification is critical for the design of sustainable fisheries and appropriate management plans, especially since not all species are equally sensitive to fishing pressure (Walker & Hislop 1998). The identification of species constitutes the first basic step for biodiversity monitoring and conservation (Dayrat B et al., 2005). More recently, mtDNA sequencing has also been used for species identification and its use has become widespread under the DNA Barcode initiative (e.g. Hebert et al. 2003a, 2003b; Ward et al. 2005, 2008a; Moura et al 2008; Steinke et al. 2009). The aims of this work were: 1) identify sharks and skates species using DNA barcode; 2) compare species of different provenance; 3) use DNA barcode for misidentified species. Using DNA barcode 15 species of sharks (Alopias vulpinus, Centrophorus granulosus, Cetorhinus maximus, Dalatias licha, Etmopterus spinax, Galeorhinus galeus, Galeus melastomus, Heptranchias perlo, Hexanchus griseus, Mustelus mustelus, Mustelus punctulatus, Oxynotus centrina, Scyliorhinus canicula Squalus acanthias, Squalus blainville), 1 species of chimaera (Chimaera monstrosa) and 21 species of rays/skayes (Dasyatis centroura, Dasyatis pastinaca, Dasyatis sp., Dipturus nidarosiensis, Dipturus oxyrinchus, Leucoraja circularis, Leucoraja melitensis, Myliobatis aquila, Pteromylaeus bovinus, Pteroplatytrygon violacea, Raja asterias, Raja brachyura, Raja clavata, Raja miraletus, Raja montagui, Raja radula, Raja polystigma, Raja undulata, Rostroraja alba, Torpedo marmorata, Torpedo nobiliana, Torpedo torpedo) was identified.

Evolution and historical biogeography of the Eastern Atlantic skates

In my thesis, I tested the hypothesis that the diversification of the Eastern Atlantic skate faunas arose through vicariance rather than dispersal, using combined approach of molecular phylogeny reconstruction and zoogeography (namely historical biogeography). This analyses have been carried out independently on four Rajidae genera belonging to two different tribes: Rajini (Raja and Dipturus) and Amblyrajini (Rajella and Leucoraja). These taxa were selected because they displayed high species diversity and richness of endemic species in the Eastern Atlantic and Mediterranean. The verification of this hypothesis was carried out by reconstructing the best phylogenetic relationships among four genera and 26 species (including several endemism) based on mtDNA and nuDNA gene variation and several statistical approaches. Divergence times of taxa have been estimated based on molecular clock and fossil calibration to explain evolutionary patterns in the context of geological framework. Main issues are (i) the evidence that Eastern Atlantic skate evolution and displacement of species diversity occurred from pulsed geographical speciation (i.e. repeated series of parallel and independent speciation events) started in the Late Eocene-Early Miocene and they have occurred prevalently during Miocene; (ii) such relatively ancient origin of diversification has been allowed the sympatric displacement and evolution of several congeneric taxa likely because they have accumulated huge differences in the genomic and physiological/behavioural phenotypic traits; (iii) recently diverged sister species and taxa showed allopatric or parapatric evolution by the presence of oceanographic or hydrogeographical barriers which likely prevent large mixing between parapatric sister species.

Therapeutic vaccination for chronic hepatitis B in the Trimera mouse model

Therapeutic vaccination for chronic hepatitis B in the Trimera mouse modelrnRaja Vuyyuru and Wulf O. BöcherrnHepatitis B is a liver disease caused by Hepatitis B virus (HBV). It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead either to liver disease or liver cancer. Acute infection is self limiting in most adults, resulting in clearance of virus from blood and liver and the development of lasting immunity. However 5% of acutely infected patients do not resolve primary HBV infection, leading to chronic infection with persistent viral replication in the liver. The strength of the initial antiviral immune response elicited to Hepatitis B determines the subsequent clinical outcome. A strong and broad T cell response leads to spontaneous resolution. Conversely, a weak T cell response favours viral persistence and establishment of chronic disease. While treatments using interferon-alpha or nucleos(t)ide analogues can reduce disease progression, they rarely lead to complete recovery. The lack of a suitable small animal model hampered efforts to understand the mechanisms responsible for immune failure in these chronic patients.rnIn current study we used Trimera mice to study the efficacy of potential vaccine candidates using HBV loaded dendritic cells in HBV chronic infection in vivo. The Trimera mouse model is based on Balb/c mice implanted with SCID mouse bone marrow and human peripheral blood mononuclear cells (PBMC) from HBV patients, and thus contains the immune system of the donor including their HBV associated T cell defect.rnIn our present study, strong HBV specific CD4+ and CD8+ T cell responses were enhanced by therapeutic vaccination in chronic HBV patients. These T cell responses occurred independently of either the course of the disease or the strength of their underlying HBV specific T cell failure. These findings indicate that the Trimera mouse model represents a novel experimental tool for evaluating potential anti-HBV immunotherapeutic agents. This in vivo data indicated that both the HBV specific CD4+ cell and CD8+ responses were elicited in the periphery. These HBV specific T cells proliferated and secreted cytokines upon restimulation in Trimera mice. The observation that these HBV specific T cells are not detectable directly ex vivo indicates that they must be immune tolerant or present at a very low frequency in situ. HBV specific T cell responses were suppressed in Trimera mice under viremic conditions, suggesting that viral factors might be directly involved in tolerizing or silencing antiviral T cell responses. Thus, combination of an effective vaccine with antiviral treatment to reduce viremia might be a more effective therapeutic strategy for the future. Such approaches should be tested in Trimera mice generated in HBV or HBs expressing transgenic mice before conducting clinical trials.rn

Molecular phylogeny and historical zoogeography of four genera of Eastern Atlantic skates (Rajiformes, Rajidae)

The aim of this study was to reconstruct a solid phylogeny of four genera of the Rajidae family (Chondrichthyans: Batoidea) using a concatenated alignment of mtDNA genes. Then use the resultant tree to estimate divergence time between taxa based on molecular clock and fossil calibration and conduct biogeographic analysis. The intent was to prove that the actual distribution of species of Eastern Atlantic and Mediterranean skates is due to a series of vicariant events. The species considered belongs to two different tribe: Rajini (Raja and Dipturus) and Amblyrajini (Leucoraja and Rajella). The choice of this genera is due to their high presence in the area of interest and to the richness of endemic species. The results show that despite the ancient origin of Rajidae (97 MYA), the Eastern Atlantic and Mediterranean faunas originated more recently, during Middle Miocene-Late Pliocene, after the closure of connection between these areas and the Indo-Pacific ocean (15 MYA). The endemic species of the Mediterranean (Raja asterias, R. radula, R. polystigma and Leucoraja melitensis) originated after the Messinian salinity crisis (7-5 MYA), when the recolonization of the basin occurred, and are still maintained in allopatric distribution by the presence of biogeographic barriers. Moreover from 4 to 2.6 MYA we can observe the formation of sister species for Raja, Leucoraja and Rajella, one of which has a Northern distribution, and the other has a Southern distribution (R. clavata vs R. straeleni, L. wallacei vs L. naevus, R. fyllae vs R. caudaspinosa and R. kukujevi vs R. leopardus + R. barnardi). The Quaternary and present oceanographic discontinuities that occur along the western African continental shelf (e.g., Cape Blanc and the Angola–Benguela Front) might contribute to the maintenance of low or null levels of gene flow between these closely related siblings species. Also sympatric speciation must be invoked to explain the evolution of skates, for example for the division between R. leopardus and R. barnardi. The speciation processes followed a south-to-north pathways for Dipturus and a north-to-south pathways for Raja, Leucoraja and Rajella underling that the evolution of the genera occurred independently. In the end, it is conceivable that the evolutionary pathways of the tribes followed the costal line during the gondwana fragmentation. The results demonstrate that the evolution of this family is characterized by a series of parallel and independent speciation events, strictly correlated to the tectonic movement of continental masses and paleogeographic and paleoclimatic events and so can be explained by a panbiogeographical (vicariance) model.

Membrane dysfunction in Andersen-Tawil syndrome assessed by velocity recovery cycles

Andersen-Tawil syndrome (ATS) due to Kir2.1mutations typically manifests as periodic paralysis, cardiac arrhythmias and developmental abnormalities but is often difficult to diagnose clinically. This study was undertaken to determine whether sarcolemmal dysfunction could be identified with muscle velocity recovery cycles (MVRCs).

The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6

The proinflammatory cytokine IL-6 seems to have an important role in the intestinal inflammation that characterizes inflammatory bowel diseases (IBDs) such as Crohn disease and ulcerative colitis. However, little is known about the molecular mechanisms regulating IL-6 production in IBD. Here, we assessed the role of the transcriptional regulator IFN regulatory factor-4 (IRF4) in this process. Patients with either Crohn disease or ulcerative colitis exhibited increased IRF4 expression in lamina propria CD3+ T cells as compared with control patients. Consistent with IRF4 having a regulatory function in T cells, in a mouse model of IBD whereby colitis is induced in RAG-deficient mice by transplantation with CD4+CD45RB(hi) T cells, adoptive transfer of wild-type but not IRF4-deficient T cells resulted in severe colitis. Furthermore, IRF4-deficient mice were protected from T cell-dependent chronic intestinal inflammation in trinitrobenzene sulfonic acid- and oxazolone-induced colitis. In addition, IRF4-deficient mice with induced colitis had reduced mucosal IL-6 production, and IRF4 was required for IL-6 production by mucosal CD90+ T cells, which it protected from apoptosis. Finally, the protective effect of IRF4 deficiency could be abrogated by systemic administration of either recombinant IL-6 or a combination of soluble IL-6 receptor (sIL-6R) plus IL-6 (hyper-IL-6). Taken together, our data identify IRF4 as a key regulator of mucosal IL-6 production in T cell-dependent experimental colitis and suggest that IRF4 might provide a therapeutic target for IBDs.

An investigation of phenolic glycoside and condensed tannin homeostasis in Populus by salicyl alcohol feeding to cell cultures and by transgenic manipulation of the sucrose transporter, PTSUT4, in planta

Secondary metabolites play an important role in plant protection against biotic and abiotic stress. In Populus, phenolic glycosides (PGs) and condensed tannins (CTs) are two such groups of compounds derived from the common phenylpropanoid pathway. The basal levels and the inducibility of PGs and CTs depend on genetic as well as environmental factors, such as soil nitrogen (N) level. Carbohydrate allocation, transport and sink strength also affect PG and CT levels. A negative correlation between the levels of PGs and CTs was observed in several studies. However, the molecular mechanism underlying such relation is not known. We used a cell culture system to understand negative correlation of PGs and CTs. Under normal culture conditions, neither salicin nor higher-order PGs accumulated in cell cultures. Several factors, such as hormones, light, organelles and precursors were discussed in the context of aspen suspension cells’ inability to synthesize PGs. Salicin and its isomer, isosalicin, were detected in cell cultures fed with salicyl alcohol, salicylaldehyde and helicin. At higher levels (5 mM) of salicyl alcohol feeding, accumulation of salicins led to reduced CT production in the cells. Based on metabolic and gene expression data, the CT reduction in salicin-accumulating cells is partly a result of regulatory changes at the transcriptional level affecting carbon partitioning between growth processes, and phenylpropanoid CT biosynthesis. Based on molecular studies, the glycosyltransferases, GT1-2 and GT1-246, may function in glycosylation of simple phenolics, such as salicyl alcohol in cell cultures. The uptake of such glycosides into vacuole may be mediated to some extent by tonoplast localized multidrug-resistance associated protein transporters, PtMRP1 and PtMRP6. In Populus, sucrose is the common transported carbohydrate and its transport is possibly regulated by sucrose transporters (SUTs). SUTs are also capable of transporting simple PGs, such as salicin. Therefore, we characterized the SUT gene family in Populus and investigated, by transgenic analysis, the possible role of the most abundantly expressed member, PtSUT4, in PG-CT homeostasis using plants grown under varying nitrogen regimes. PtSUT4 transgenic plants were phenotypically similar to the wildtype plants except that the leaf area-to-stem volume ratio was higher for transgenic plants. In SUT4 transgenics, levels of non-structural carbohydrates, such as sucrose and starch, were altered in mature leaves. The levels of PGs and CTs were lower in green tissues of transgenic plants under N-replete, but were higher under N-depleted conditions, compared to the levels in wildtype plants. Based on our results, SUT4 partly regulates N-level dependent PG-CT homeostasis by differential carbohydrate allocation.