A physical upper limit on the HI column density of gas clouds

An intriguing fact about cosmic gas clouds is that they all appear to have neutral (atomic) hydrogen column densities smaller than 10^{22} cm^{-2}. Observations of damped Ly-alpha (DLA) absorption systems further indicate that the maximum N(HI) decreases with increasing metallicity. It is generally assumed that this trend is due to a dust-induced selection bias: DLA systems with high N(HI) and high metallicity contain so much dust that the background QSO becomes too dim to be included in optically selected surveys. Here, it is argued that this explanation may not be viable. Instead, it is proposed that conversion to molecular hydrogen determines the maximum HI column density. Molecular hydrogen forms on the surface of dust grains and is destroyed by photodissociation. Therefore, the molecular fraction correlates with both the dust content and, because of self-shielding, the total hydrogen column density, and anticorrelates with the intensity of the incident UV radiation. It is shown that the first relation can account for the observed anticorrelation between the maximum N(HI) and metallicity.Comment: Accepted for publication in the Astrophysical Journal Letters. 4 pages, 2 figures. Minor change

Four-Body Bound State Calculations in Three-Dimensional Approach

The four-body bound state with two-body interactions is formulated in Three-Dimensional approach, a recently developed momentum space representation which greatly simplifies the numerical calculations of few-body systems without performing the partial wave decomposition. The obtained three-dimensional Faddeev-Yakubovsky integral equations are solved with two-body potentials. Results for four-body binding energies are in good agreement with achievements of the other methods.Comment: 29 pages, 2 eps figures, 8 tables, REVTeX

Benchmark Test Calculation of a Four-Nucleon Bound State

In the past, several efficient methods have been developed to solve the Schroedinger equation for four-nucleon bound states accurately. These are the Faddeev-Yakubovsky, the coupled-rearrangement-channel Gaussian-basis variational, the stochastic variational, the hyperspherical variational, the Green's function Monte Carlo, the no-core shell model and the effective interaction hyperspherical harmonic methods. In this article we compare the energy eigenvalue results and some wave function properties using the realistic AV8' NN interaction. The results of all schemes agree very well showing the high accuracy of our present ability to calculate the four-nucleon bound state.Comment: 17 pages, 1 figure

State Dependent Effective Interaction for the Hyperspherical Formalism

The method of effective interaction, traditionally used in the framework of an harmonic oscillator basis, is applied to the hyperspherical formalism of few-body nuclei (A=3-6). The separation of the hyperradial part leads to a state dependent effective potential. Undesirable features of the harmonic oscillator approach associated with the introduction of a spurious confining potential are avoided. It is shown that with the present method one obtains an enormous improvement of the convergence of the hyperspherical harmonics series in calculating ground state properties, excitation energies and transitions to continuum states.Comment: LaTeX, 16 pages, 8 ps figure

On the variation of the fine-structure constant: Very high resolution spectrum of QSO HE 0515-4414

We present a detailed analysis of a very high resolution (R\approx 112,000) spectrum of the quasar HE 0515-4414 obtained using the High Accuracy Radial velocity Planet Searcher (HARPS) mounted on the ESO 3.6 m telescope at the La Silla observatory. The HARPS spectrum, of very high wavelength calibration accuracy (better than 1 m\AA), is used to search for possible systematic inaccuracies in the wavelength calibration of the UV Echelle Spectrograph (UVES) mounted on the ESO Very Large Telescope (VLT). We have carried out cross-correlation analysis between the Th-Ar lamp spectra obtained with HARPS and UVES. The shift between the two spectra has a dispersion around zero of \sigma\simeq 1 m\AA. This is well within the wavelength calibration accuracy of UVES (i.e \sigma\simeq 4 m\AA). We show that the uncertainties in the wavelength calibration induce an error of about, \Delta\alpha/\alpha\le 10^{-6}, in the determination of the variation of the fine-structure constant. Thus, the results of non-evolving \Delta\alpha/\alpha reported in the literature based on UVES/VLT data should not be heavily influenced by problems related to wavelength calibration uncertainties. Our higher resolution spectrum of the z_{abs}=1.1508 damped Lyman-\alpha system toward HE 0515-4414 reveals more components compared to the UVES spectrum. Using the Voigt profile decomposition that simultaneously fits the high resolution HARPS data and the higher signal-to-noise ratio UVES data, we obtain, \Delta\alpha/\alpha=(0.05\pm0.24)x10^{-5} at z_{abs}=1.1508. This result is consistent with the earlier measurement for this system using the UVES spectrum alone.Comment: 14 pages, 13 figures, Accepted in A&

The Clostridium difficile Cell Wall Protein CwpV is Antigenically Variable between Strains, but Exhibits Conserved Aggregation-Promoting Function

Clostridium difficile is the main cause of antibiotic-associated diarrhea, leading to significant morbidity and mortality and putting considerable economic pressure on healthcare systems. Current knowledge of the molecular basis of pathogenesis is limited primarily to the activities and regulation of two major toxins. In contrast, little is known of mechanisms used in colonization of the enteric system. C. difficile expresses a proteinaceous array on its cell surface known as the S-layer, consisting primarily of the major S-layer protein SlpA and a family of SlpA homologues, the cell wall protein (CWP) family. CwpV is the largest member of this family and is expressed in a phase variable manner. Here we show CwpV promotes C. difficile aggregation, mediated by the C-terminal repetitive domain. This domain varies markedly between strains; five distinct repeat types were identified and were shown to be antigenically distinct. Other aspects of CwpV are, however, conserved. All CwpV types are expressed in a phase variable manner. Using targeted gene knock-out, we show that a single site-specific recombinase RecV is required for CwpV phase variation. CwpV is post-translationally cleaved at a conserved site leading to formation of a complex of cleavage products. The highly conserved N-terminus anchors the CwpV complex to the cell surface. Therefore CwpV function, regulation and processing are highly conserved across C. difficile strains, whilst the functional domain exists in at least five antigenically distinct forms. This hints at a complex evolutionary history for CwpV

Anti-cancer drug validation: the contribution of tissue engineered models

Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Dynamic, Large-Scale Profiling of Transcription Factor Activity from Live Cells in 3D Culture

phenotypes. Taken together, our objective was to develop cellular arrays for dynamic, large-scale quantification of TF activity as cells organized into spherical structures within 3D culture.TF-specific and normalization reporter constructs were delivered in parallel to a cellular array containing a well-established breast cancer cell line cultured in Matrigel. Bioluminescence imaging provided a rapid, non-invasive, and sensitive method to quantify luciferase levels, and was applied repeatedly on each sample to monitor dynamic activity. Arrays measuring 28 TFs identified up to 19 active, with 13 factors changing significantly over time. Stimulation of cells with β-estradiol or activin A resulted in differential TF activity profiles evolving from initial stimulation of the ligand. Many TFs changed as expected based on previous reports, yet arrays were able to replicate these results in a single experiment. Additionally, arrays identified TFs that had not previously been linked with activin A.This system provides a method for large-scale, non-invasive, and dynamic quantification of signaling pathway activity as cells organize into structures. The arrays may find utility for investigating mechanisms regulating normal and abnormal tissue growth, biomaterial design, or as a platform for screening therapeutics