A semiconductor source of triggered entangled photon pairs?

The realisation of a triggered entangled photon source will be of great importance in quantum information, including for quantum key distribution and quantum computation. We show here that: 1) the source reported in ``A semiconductor source of triggered entangled photon pairs''[1. Stevenson et al., Nature 439, 179 (2006)]} is not entangled; 2) the entanglement indicators used in Ref. 1 are inappropriate, relying on assumptions invalidated by their own data; and 3) even after simulating subtraction of the significant quantity of background noise, their source has insignificant entanglement.Comment: 5 pages in pre-print format, 1 tabl

Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

<p>Abstract</p> <p>Background</p> <p>We propose a simple new method for estimating progression of a chronic disease with multi-state properties by unifying the prevalence pool concept with the Markov process model.</p> <p>Methods</p> <p>Estimation of progression rates in the multi-state model is performed using the E-M algorithm. This approach is applied to data on Type 2 diabetes screening.</p> <p>Results</p> <p>Good convergence of estimations is demonstrated. In contrast to previous Markov models, the major advantage of our proposed method is that integrating the prevalence pool equation (that the numbers entering the prevalence pool is equal to the number leaving it) into the likelihood function not only simplifies the likelihood function but makes estimation of parameters stable.</p> <p>Conclusion</p> <p>This approach may be useful in quantifying the progression of a variety of chronic diseases.</p

Phenotypic features and genetic characterization of male breast cancer families: identification of two recurrent BRCA2 mutations in north-east of Italy

BACKGROUND: Breast cancer in men is an infrequent occurrence, accounting for ~1% of all breast tumors with an incidence of about 1:100,000. The relative rarity of male breast cancer (MBC) limits our understanding of the epidemiologic, genetic and clinical features of this tumor. METHODS: From 1997 to 2003, 10 MBC patients were referred to our Institute for genetic counselling and BRCA1/2 testing. Here we report on the genetic and phenotypic characterization of 10 families with MBC from the North East of Italy. In particular, we wished to assess the occurrence of specific cancer types in relatives of MBC probands in families with and without BRCA2 predisposing mutations. Moreover, families with recurrent BRCA2 mutations were also characterized by haplotype analysis using 5 BRCA2-linked dinucleotide repeat markers and 8 intragenic BRCA2 polymorphisms. RESULTS: Two pathogenic mutations in the BRCA2 gene were observed: the 9106C>T (Q2960X) and the IVS16-2A>G (splicing) mutations, each in 2 cases. A BRCA1 mutation of uncertain significance 4590C>G (P1491A) was also observed. In families with BRCA2 mutations, female breast cancer was more frequent in the first and second-degree relatives compared to the families with wild type BRCA1/2 (31.9% vs. 8.0% p = 0.001). Reconstruction of the chromosome phasing in three families and the analysis of three isolated cases with the IVS16-2A>G BRCA2 mutation identified the same haplotype associated with MBC, supporting the possibility that this founder mutation previously detected in Slovenian families is also present in the North East of our Country. Moreover, analysis of one family with the 9106C>T BRCA2 mutation allowed the identification of common haplotypes for both microsatellite and intragenic polymorphisms segregating with the mutation. Three isolated cases with the same mutation shared the same intragenic polymorphisms and three 5' microsatellite markers, but showed a different haplotype for 3' markers, which were common to all three cases. CONCLUSION: The 9106C>T and the IVS16-2A>G mutations constitute recurrent BRCA2 mutations in MBC cases from the North-East of Italy and may be associated with a founder effect. Knowledge of these two recurrent BRCA2 mutations predisposing to MBC may facilitate the analyses aimed at the identification of mutation carriers in our geographic area

MISHIMA - a new method for high speed multiple alignment of nucleotide sequences of bacterial genome scale data

<p>Abstract</p> <p>Background</p> <p>Large nucleotide sequence datasets are becoming increasingly common objects of comparison. Complete bacterial genomes are reported almost everyday. This creates challenges for developing new multiple sequence alignment methods. Conventional multiple alignment methods are based on pairwise alignment and/or progressive alignment techniques. These approaches have performance problems when the number of sequences is large and when dealing with genome scale sequences.</p> <p>Results</p> <p>We present a new method of multiple sequence alignment, called MISHIMA (Method for Inferring Sequence History In terms of Multiple Alignment), that does not depend on pairwise sequence comparison. A new algorithm is used to quickly find rare oligonucleotide sequences shared by all sequences. Divide and conquer approach is then applied to break the sequences into fragments that can be aligned independently by an external alignment program. These partial alignments are assembled together to form a complete alignment of the original sequences.</p> <p>Conclusions</p> <p>MISHIMA provides improved performance compared to the commonly used multiple alignment methods. As an example, six complete genome sequences of bacteria species <it>Helicobacter pylori </it>(about 1.7 Mb each) were successfully aligned in about 6 hours using a single PC.</p

Enterovirus 71 3C Protease Cleaves a Novel Target CstF-64 and Inhibits Cellular Polyadenylation

Identification of novel cellular proteins as substrates to viral proteases would provide a new insight into the mechanism of cell–virus interplay. Eight nuclear proteins as potential targets for enterovirus 71 (EV71) 3C protease (3Cpro) cleavages were identified by 2D electrophoresis and MALDI-TOF analysis. Of these proteins, CstF-64, which is a critical factor for 3′ pre-mRNA processing in a cell nucleus, was selected for further study. A time-course study to monitor the expression levels of CstF-64 in EV71-infected cells also revealed that the reduction of CstF-64 during virus infection was correlated with the production of viral 3Cpro. CstF-64 was cleaved in vitro by 3Cpro but neither by mutant 3Cpro (in which the catalytic site was inactivated) nor by another EV71 protease 2Apro. Serial mutagenesis was performed in CstF-64, revealing that the 3Cpro cleavage sites are located at position 251 in the N-terminal P/G-rich domain and at multiple positions close to the C-terminus of CstF-64 (around position 500). An accumulation of unprocessed pre-mRNA and the depression of mature mRNA were observed in EV71-infected cells. An in vitro assay revealed the inhibition of the 3′-end pre-mRNA processing and polyadenylation in 3Cpro-treated nuclear extract, and this impairment was rescued by adding purified recombinant CstF-64 protein. In summing up the above results, we suggest that 3Cpro cleavage inactivates CstF-64 and impairs the host cell polyadenylation in vitro, as well as in virus-infected cells. This finding is, to our knowledge, the first to demonstrate that a picornavirus protein affects the polyadenylation of host mRNA

Viral non-coding RNA inhibits HNF4α expression in HCV associated hepatocellular carcinoma

BACKGROUND: Hepatitis C virus (HCV) infection is an established cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC); however, it is unclear if the virus plays a direct role in the development of HCC. Hepatocyte nuclear factor 4α (HNF4α) is critical determinant of epithelial architecture and hepatic development; depletion of HNF4α is correlated with oncogenic transformation. We explored the viral role in the inhibition of HNF4α expression, and consequent induction of tumor-promoting genes in HCV infection-associated HCC. METHODS: Western blot analysis was used to monitor the changes in expression levels of oncogenic proteins in liver tissues from HCV-infected humanized mice. The mechanism of HNF4α depletion was studied in HCV-infected human hepatocyte cultures in vitro. Targeting of HNF4α expression by viral non-coding RNA was examined by inhibition of Luciferase HNF4α 3’-UTR reporter. Modulation of invasive properties of HCV-infected cells was examined by Matrigel cell migration assay. RESULTS: Results show inhibition of HNF4α expression by targeting of HNF4α 3’-UTR by HCV-derived small non-coding RNA, vmr11. Vmr11 enhances the invasive properties of HCV-infected cells. Loss of HNF4α in HCV-infected liver tumors of humanized mice correlates with the induction of epithelial to mesenchymal transition (EMT) genes. CONCLUSIONS: We show depletion of HNF4α in liver tumors of HCV-infected humanized mice by HCV derived small non-coding RNA (vmr11) and resultant induction of EMT genes, which are critical determinants of tumor progression. These results suggest a direct viral role in the development of hepatocellular carcinoma

The SunPy Project: Open Source Development and Status of the Version 1.0 Core Package

The goal of the SunPy project is to facilitate and promote the use and development of community-led, free, and open source data analysis software for solar physics based on the scientific Python environment. The project achieves this goal by developing and maintaining the sunpy core package and supporting an ecosystem of affiliated packages. This paper describes the first official stable release (version 1.0) of the core package, as well as the project organization and infrastructure. This paper concludes with a discussion of the future of the SunPy project

SNAI2/Slug promotes growth and invasion in human gliomas

<p>Abstract</p> <p>Background</p> <p>Numerous factors that contribute to malignant glioma invasion have been identified, but the upstream genes coordinating this process are poorly known.</p> <p>Methods</p> <p>To identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles of primary human glioblastomas to develop an expression-based rank ordering of 30 transcription factors that have previously been implicated in the regulation of invasion and metastasis in cancer.</p> <p>Results</p> <p>Using this approach, we identified the oncogenic transcriptional repressor, <it>SNAI2</it>/Slug, among the upper tenth percentile of invasion-related transcription factors overexpressed in glioblastomas. <it>SNAI2 </it>mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells. Overexpression of <it>SNAI2/</it>Slug increased glioblastoma cell proliferation and invasion <it>in vitro </it>and promoted angiogenesis and glioblastoma growth <it>in vivo</it>. Importantly, knockdown of endogenous <it>SNAI2</it>/Slug in glioblastoma cells decreased invasion and increased survival in a mouse intracranial human glioblastoma transplantation model.</p> <p>Conclusion</p> <p>This genome-scale approach has thus identified <it>SNAI2</it>/Slug as a regulator of growth and invasion in human gliomas.</p

Tidal and groundwater fluxes to a shallow, microtidal estuary : constraining inputs through field observations and hydrodynamic modeling

This paper is not subject to U.S. copyright. The definitive version was published in Estuaries and Coasts 35 (2012): 1285-1298, doi:10.1007/s12237-012-9515-x.Increased nutrient loading to estuaries has led to eutrophication, degraded water quality, and ecological transformations. Quantifying nutrient loads in systems with significant groundwater input can be difficult due to the challenge of measuring groundwater fluxes. We quantified tidal and freshwater fluxes over an 8-week period at the entrance of West Falmouth Harbor, Massachusetts, a eutrophic, groundwater-fed estuary. Fluxes were estimated from velocity and salinity measurements and a total exchange flow (TEF) methodology. Intermittent cross-sectional measurements of velocity and salinity were used to convert point measurements to cross-sectionally averaged values over the entire deployment (index relationships). The estimated mean freshwater flux (0.19 m3/s) for the 8-week period was mainly due to groundwater input (0.21 m3/s) with contributions from precipitation to the estuary surface (0.026 m3/s) and removal by evaporation (0.048 m3/s). Spring–neap variations in freshwater export that appeared in shorter-term averages were mostly artifacts of the index relationships. Hydrodynamic modeling with steady groundwater input demonstrated that while the TEF methodology resolves the freshwater flux signal, calibration of the index– salinity relationships during spring tide conditions only was responsible for most of the spring–neap signal. The mean freshwater flux over the entire period estimated from the combination of the index-velocity, index–salinity, and TEF calculations were consistent with the model, suggesting that this methodology is a reliable way of estimating freshwater fluxes in the estuary over timescales greater than the spring– neap cycle. Combining this type of field campaign with hydrodynamic modeling provides guidance for estimating both magnitude of groundwater input and estuarine storage of freshwater and sets the stage for robust estimation of the nutrient load in groundwater.Funding was provided by the USGS Coastal and Marine Geology Program and by National Science Foundation Award #0420575 from the Biocomplexity/Coupled Biogeochemical Cycles Program