1,237 research outputs found
Planar Drawings of Fixed-Mobile Bigraphs
A fixed-mobile bigraph G is a bipartite graph such that the vertices of one
partition set are given with fixed positions in the plane and the mobile
vertices of the other part, together with the edges, must be added to the
drawing. We assume that G is planar and study the problem of finding, for a
given k >= 0, a planar poly-line drawing of G with at most k bends per edge. In
the most general case, we show NP-hardness. For k=0 and under additional
constraints on the positions of the fixed or mobile vertices, we either prove
that the problem is polynomial-time solvable or prove that it belongs to NP.
Finally, we present a polynomial-time testing algorithm for a certain type of
"layered" 1-bend drawings
A Dual-Readout F2 Assay That Combines Fluorescence Resonance Energy Transfer and Fluorescence Polarization for Monitoring Bimolecular Interactions
Forster (fluorescence) resonance energy transfer (FRET) and fluorescence polarization (FP) are widely used technologies for monitoring bimolecular interactions and have been extensively used in high-throughput screening (HTS) for probe and drug discovery. Despite their popularity in HTS, it has been recognized that different assay technologies may generate different hit lists for the same biochemical interaction. Due to the high cost of large-scale HTS campaigns, one has to make a critical choice to employee one assay platform for a particular HTS. Here we report the design and development of a dual-readout HTS assay that combines two assay technologies into one system using the Mcl-1 and Noxa BH3 peptide interaction as a model system. In this system, both FP and FRET signals were simultaneously monitored from one reaction, which is termed -Dual-Readout F2 assay- with F2 for FP and FRET. This dual-readout technology has been optimized in a 1,536-well ultra-HTS format for the discovery of Mcl-1 protein inhibitors and achieved a robust performance. This F2 assay was further validated by screening a library of 102,255 compounds. As two assay platforms are utilized for the same target simultaneously, hit information is enriched without increasing the screening cost. This strategy can be generally extended to other FP-based assays and is expected to enrich primary HTS information and enhance the hit quality of HTS campaigns.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90469/1/adt-2E2010-2E0292.pd
Content Disputes in Wikipedia Reflect Geopolitical Instability
Indicators that rank countries according socioeconomic measurements are important tools for regional development and political reform. Those currently in widespread use are sometimes criticized for a lack of reproducibility or the inability to compare values over time, necessitating simple, fast and systematic measures. Here, we applied the ‘guilt by association’ principle often used in biological networks to the information network within the online encyclopedia Wikipedia to create an indicator quantifying the degree to which pages linked to a country are disputed by contributors. The indicator correlates with metrics of governance, political or economic stability about as well as they correlate with each other, and though faster and simpler, it is remarkably stable over time despite constant changes in the underlying disputes. For some countries, changes over a four year period appear to correlate with world events related to conflicts or economic problems
Institutional reform and FDI decision in transition economies: a qualitative study of Syria
The article considers the impact of institutional reform on the decision of foreign enterprises and foreign entrepreneurs
to directly invest in the transition economy of Syria. It responds to the calls for more open research design that can go
beyond the borders of the quantitative findings of previous econometric research by adopting a qualitative research
strategy. The results reveal that institutional reforms enhanced Syria’s attractiveness to foreign direct investment.
Institutional barriers proved to be less daunting to foreign investors whose backgrounds were culturally similar to that
of Syria and/or already had experience in Syria or in a similar type of economy. The impact of background similarity and
previous experience in similar contexts appeared to be less important when the foreign investor was a multinational
enterprise than for individual entrepreneur. Moreover, these factors also appeared to be less important for large
enterprises compared to small enterprises
Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials
Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen
85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and
second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There
are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG.
These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG
alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety
and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A
boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination
was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when
administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were
compared with the previous long interval trial data, there were no significant differences in the magnitude of immune
responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The
clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses.
This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These
findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial
immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data
presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here
Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma
Napsin A is an aspartic proteinase expressed in lung and kidney. We have reported that napsin A is expressed in type II pneumocytes and in adenocarcinomas of the lung. The expression of napsin was examined in 118 lung tissues including 16 metastases by in situ hybridisation. Napsin was expressed in the tumour cell compartment in 33 of 39 adenocarcinomas (84.6%), in two of 11 large cell carcinomas and in one lung metastasis of a renal cell carcinoma. Expression of napsin was found to be associated with a high degree of differentiation in adenocarcinoma. Immunohistochemistry was performed for three proteins currently used as markers for lung adenocarcinoma : surfactant protein-A, surfactant protein-B and thyroid transcription factor-1. Thyroid transcription factor-1 showed the same sensitivity (84.6%) as napsin for adenocarcinoma, whereas surfactant protein-A and surfactant protein-B showed lower sensitivities. Among these markers, napsin showed the highest specificity (94.3%) for adenocarcinoma in nonsmall cell lung carcinoma. We conclude that napsin is a promising marker for the diagnosis of primary lung adenocarcinoma
BP1 transcriptionally activates bcl-2 and inhibits TNFα-induced cell death in MCF7 breast cancer cells
Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.
BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials
The synthetic inhibitor of Fibroblast Growth Factor Receptor PD166866 controls negatively the growth of tumor cells in culture
<p>Abstract</p> <p>Background</p> <p>Many experimental data evidence that over-expression of various growth factors cause disorders in cell proliferation. The role of the Fibroblast Growth Factors (FGF) in growth control is indisputable: in particular, FGF1 and its tyrosine kinase receptor (FGFR1) act through a very complex network of mechanisms and pathways. In this work we have evaluated the antiproliferative activity effect of PD166866, a synthetic molecule inhibiting the tyrosin kinase action of FGFR1.</p> <p>Methods</p> <p>Cells were routinely grown in Dulbecco Modified Eagle's medium supplemented with newborn serum and a penicillin-streptomycin mixture.</p> <p>Cell viability was evaluated by Mosmann assay and by trypan blue staining. DNA damage was assessed by <it>in situ </it>fluorescent staining with Terminal Deoxynucleotidyl Transferase dUTP nick end labeling (TUNEL assay).</p> <p>Assessment of oxidative stress at membrane level was measured by quantitative analysis of the intra-cellular formation of malonyl-dialdheyde (MDA) deriving from the decomposition of poly-unsaturated fatty acids.</p> <p>The expression of Poly-ADP-Ribose-Polymerase (PARP), consequent to DNA fragmentation, was evidenced by immuno-histochemistry utilizing an antibody directed against an N-terminal fragment of the enzyme.</p> <p>Results</p> <p>The bioactivity of the drug was investigated on Hela cells. Cytoxicity was assessed by the Mosmann assay and by vital staining with trypan blue. The target of the molecule is most likely the cell membrane as shown by the significant increase of the intracellular concentration of malonyl-dihaldheyde. The increase of this compound, as a consequence of the treatment with PD166866, is suggestive of membrane lipoperoxidation. The TUNEL assay gave a qualitative, though clear, indication of DNA damage. Furthermore we demonstrate intracellular accumulation of poly-ADP-ribose polymerase I. This enzyme is a sensor of nicks on the DNA strands and this supports the idea that treatment with the drug induces cell death.</p> <p>Conclusions</p> <p>Data presented in this work show that PD166866 has clear antiproliferative effects. The negative control of cell proliferation may be exerted through the activation of the apoptotic pathway. The results of experiments addressing this specific point, such as: evaluation of DNA damage, lipoperoxidation of the cell membrane and increase of expression of PARP, an enzyme directly involved in DNA repair. Results suggest that cells exposed to PD16866 undergo apoptosis. However, concomitant modes of cell death cannot be ruled out. The possible use of this drug for therapeutic purposes is discussed.</p
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