Structure and stability of a high-coverage (1x1) oxygen phase on Ru(0001)

The formation of chemisorbed O-phases on Ru(0001) by exposure to O_2 at low pressures is apparently limited to coverages Theta <= 0.5. Using low-energy electron diffraction and density functional theory we show that this restriction is caused by kinetic hindering and that a dense O overlayer (Theta = 1) can be formed with a (1x1) periodicity. The structural and energetic properties of this new adsorbate phase are analyzed and discussed in view of attempts to bridge the so-called "pressure gap" in heterogeneous catalysis. It is argued that the identified system actuates the unusually high rate of oxidizing reactions at Ru surfaces under high oxygen pressure conditions.Comment: RevTeX, 6 pages, 3 figures, to appear in Phys. Rev. Let

The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus

<p>Abstract</p> <p>Background</p> <p>Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity.</p> <p>Methods</p> <p>The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results.</p> <p>Results</p> <p>Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3) deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time.</p> <p>Conclusions</p> <p>Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.</p

OntoDas – a tool for facilitating the construction of complex queries to the Gene Ontology

<p>Abstract</p> <p>Background</p> <p>Ontologies such as the Gene Ontology can enable the construction of complex queries over biological information in a conceptual way, however existing systems to do this are too technical. Within the biological domain there is an increasing need for software that facilitates the flexible retrieval of information. OntoDas aims to fulfil this need by allowing the definition of queries by selecting valid ontology terms.</p> <p>Results</p> <p>OntoDas is a web-based tool that uses information visualisation techniques to provide an intuitive, interactive environment for constructing ontology-based queries against the Gene Ontology Database. Both a comprehensive use case and the interface itself were designed in a participatory manner by working with biologists to ensure that the interface matches the way biologists work. OntoDas was further tested with a separate group of biologists and refined based on their suggestions.</p> <p>Conclusion</p> <p>OntoDas provides a visual and intuitive means for constructing complex queries against the Gene Ontology. It was designed with the participation of biologists and compares favourably with similar tools. It is available at <url>http://ontodas.nbn.ac.za</url></p

Real Space Observations of Magnesium Hydride Formation and Decomposition

The mechanisms of magnesium hydride formation and thermal decomposition are directly examined using in-situ imaging.Comment: 3 pages, 4 figure

Oxygen adsorption on the Ru (10 bar 1 0) surface: Anomalous coverage dependence

Oxygen adsorption onto Ru (10 bar 1 0) results in the formation of two ordered overlayers, i.e. a c(2 times 4)-2O and a (2 times 1)pg-2O phase, which were analyzed by low-energy electron diffraction (LEED) and density functional theory (DFT) calculation. In addition, the vibrational properties of these overlayers were studied by high-resolution electron loss spectroscopy. In both phases, oxygen occupies the threefold coordinated hcp site along the densely packed rows on an otherwise unreconstructed surface, i.e. the O atoms are attached to two atoms in the first Ru layer Ru(1) and to one Ru atom in the second layer Ru(2), forming zigzag chains along the troughs. While in the low-coverage c(2 times 4)-O phase, the bond lengths of O to Ru(1) and Ru(2) are 2.08 A and 2.03 A, respectively, corresponding bond lengths in the high-coverage (2 times 1)-2O phase are 2.01 A and 2.04 A (LEED). Although the adsorption energy decreases by 220 meV with O coverage (DFT calculations), we observe experimentally a shortening of the Ru(1)-O bond length with O coverage. This effect could not be reconciled with the present DFT-GGA calculations. The nu(Ru-O) stretch mode is found at 67 meV [c(2 times 4)-2O] and 64 meV [(2 times 1)pg-2O].Comment: 10 pages, figures are available as hardcopies on request by mailing [email protected], submitted to Phys. Rev. B (8. Aug. 97), other related publications can be found at http://www.rz-berlin.mpg.de/th/paper.htm

The SARS-coronavirus-host interactome

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

XNAP: Making LSTM-based Next Activity Predictions Explainable by Using LRP

Predictive business process monitoring (PBPM) is a class of techniques designed to predict behaviour, such as next activities, in running traces. PBPM techniques aim to improve process performance by providing predictions to process analysts, supporting them in their decision making. However, the PBPM techniques` limited predictive quality was considered as the essential obstacle for establishing such techniques in practice. With the use of deep neural networks (DNNs), the techniques` predictive quality could be improved for tasks like the next activity prediction. While DNNs achieve a promising predictive quality, they still lack comprehensibility due to their hierarchical approach of learning representations. Nevertheless, process analysts need to comprehend the cause of a prediction to identify intervention mechanisms that might affect the decision making to secure process performance. In this paper, we propose XNAP, the first explainable, DNN-based PBPM technique for the next activity prediction. XNAP integrates a layer-wise relevance propagation method from the field of explainable artificial intelligence to make predictions of a long short-term memory DNN explainable by providing relevance values for activities. We show the benefit of our approach through two real-life event logs

The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

Infection of Differentiated Porcine Airway Epithelial Cells by Influenza Virus: Differential Susceptibility to Infection by Porcine and Avian Viruses

BACKGROUND: Swine are important hosts for influenza A viruses playing a crucial role in the epidemiology and interspecies transmission of these viruses. Respiratory epithelial cells are the primary target cells for influenza viruses. METHODOLOGY/PRINCIPAL FINDINGS: To analyze the infection of porcine airway epithelial cells by influenza viruses, we established precision-cut lung slices as a culture system for differentiated respiratory epithelial cells. Both ciliated and mucus-producing cells were found to be susceptible to infection by swine influenza A virus (H3N2 subtype) with high titers of infectious virus released into the supernatant already one day after infection. By comparison, growth of two avian influenza viruses (subtypes H9N2 and H7N7) was delayed by about 24 h. The two avian viruses differed both in the spectrum of susceptible cells and in the efficiency of replication. As the H9N2 virus grew to titers that were only tenfold lower than that of a porcine H3N2 virus this avian virus is an interesting candidate for interspecies transmission. Lectin staining indicated the presence of both α-2,3- and α-2,6-linked sialic acids on airway epithelial cells. However, their distribution did not correlate with pattern of virus infection indicating that staining by plant lectins is not a reliable indicator for the presence of cellular receptors for influenza viruses. CONCLUSIONS/SIGNIFICANCE: Differentiated respiratory epithelial cells significantly differ in their susceptibility to infection by avian influenza viruses. We expect that the newly described precision-cut lung slices from the swine lung are an interesting culture system to analyze the infection of differentiated respiratory epithelial cells by different pathogens (viral, bacterial and parasitic ones) of swine

Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen

The stable infection of host macrophages by Mycobacterium tuberculosis (Mtb) involves, and depends on, the attenuation of the diverse microbicidal responses mounted by the host cell. This is primarily achieved through targeted perturbations of the host cellular signaling machinery. Therefore, in view of the dependency of the pathogen on host molecules for its intracellular survival, we wanted to test whether targeting such factors could provide an alternate route for the therapeutic management of tuberculosis. To first identify components of the host signaling machinery that regulate intracellular survival of Mtb, we performed an siRNA screen against all known kinases and phosphatases in murine macrophages infected with the virulent strain, H37Rv. Several validated targets could be identified by this method where silencing led either to a significant decrease, or enhancement in the intracellular mycobacterial load. To further resolve the functional relevance of these targets, we also screened against these identified targets in cells infected with different strains of multiple drug-resistant mycobacteria which differed in terms of their intracellular growth properties. The results obtained subsequently allowed us to filter the core set of host regulatory molecules that functioned independently of the phenotypic variations exhibited by the pathogen. Then, using a combination of both in vitro and in vivo experimentation, we could demonstrate that at least some of these host factors provide attractive targets for anti-TB drug development. These results provide a “proof-of-concept” demonstration that targeting host factors subverted by intracellular Mtb provides an attractive and feasible strategy for the development of anti-tuberculosis drugs. Importantly, our findings also emphasize the advantage of such an approach by establishing its equal applicability to infections with Mtb strains exhibiting a range of phenotypic diversifications, including multiple drug-resistance. Thus the host factors identified here may potentially be exploited for the development of anti-tuberculosis drugs