Evidence for a Galactic gamma ray halo

We present quantitative statistical evidence for a $\gamma$-ray emission halo surrounding the Galaxy. Maps of the emission are derived. EGRET data were analyzed in a wavelet-based non-parametric hypothesis testing framework, using a model of expected diffuse (Galactic + isotropic) emission as a null hypothesis. The results show a statistically significant large scale halo surrounding the center of the Milky Way as seen from Earth. The halo flux at high latitudes is somewhat smaller than the isotropic gamma-ray flux at the same energy, though of the same order (O(10^(-7)--10^(-6)) ph/cm^2/s/sr above 1 GeV).Comment: Final version accepted for publication in New Astronomy. Some additional results/discussion included, along with entirely revised figures. 19 pages, 15 figures, AASTeX. Better quality figs (PS and JPEG) are available at http://tigre.ucr.edu/halo/paper.htm

Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

Metals in Catalysis, Biomimetics & Inorganic Material

Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo

Histone deacetylation and DNA methylation have a central role in the control of gene expression in tumours, including transcriptional repression of tumour suppressor genes and genes involved in sensitivity to chemotherapy. Treatment of cisplatin-resistant cell lines with an inhibitor of DNA methyltransferases, 2-deoxy-5′azacytidine (decitabine), results in partial reversal of DNA methylation, re-expression of epigenetically silenced genes including hMLH1 and sensitisation to cisplatin both in vitro and in vivo. We have investigated whether the combination of decitabine and a clinically relevant inhibitor of histone deacetylase activity (belinostat, PXD101) can further increase the re-expression of genes epigenetically silenced by DNA methylation and enhance chemo-sensitisation in vivo at well-tolerated doses. The cisplatin-resistant human ovarian cell line A2780/cp70 has the hMLH1 gene methylated and is resistant to cisplatin both in vitro and when grown as a xenograft in mice. Treatment of A2780/cp70 with decitabine and belinostat results in a marked increase in expression of epigenetically silenced MLH1 and MAGE-A1 both in vitro and in vivo when compared with decitabine alone. The combination greatly enhanced the effects of decitabine alone on the cisplatin sensitivity of xenografts. As the dose of decitabine that can be given to patients and hence the maximum pharmacodynamic effect as a demethylating agent is limited by toxicity and eventual re-methylation of genes, we suggest that the combination of decitabine and belinostat could have a role in the efficacy of chemotherapy in tumours that have acquired drug resistance due to DNA methylation and gene silencing

Spatial Modulation or Spatial Multiplexing for mmWave Communications?

In this paper, two large scale (LS)–multiple–input multiple–output (MIMO) systems and their performance over 3D statistical outdoor millimeter wave (mmWave) channel model are considered and thoroughly analyzed. Namely, spatial multiplexing (SMX) and spatial modulation (SM) systems are considered. The performance of both systems in terms of average bit error ratio (ABER) and channel capacity are derived and studied. Obtained results divulge that SM can achieve higher theoretical capacity than SMX system. Further, SMX system is shown to offer better ABER and mutual information performance as compared to SM system for the same system configuration. Yet, SM demonstrate significant energy efficiency (EE) enhancement for large scale number of transmit antennas.© 2019 Springer. ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering.fi=vertaisarvioitu|en=peerReviewed

Linking jet emission and X-ray properties in the peculiar neutron star X-ray binary Circinus X-1

We present the results of simultaneous X-ray and radio observations of the peculiar Z-type neutron star X-ray binary Cir X-1, observed with the Rossi X-ray timing explorer satellite and the Australia Telescope Compact Array in 2000 October and 2002 December. We identify typical Z source behaviour in the power density spectra as well as characteristic Z patterns drawn in an X-ray hardness-intensity diagram. Power spectra typical of bright atoll sources have also been identified at orbital phases after the periastron passage, while orbital phases before the periastron passage are characterized by power spectra that are typical neither of Z nor of atoll sources. We investigate the coupling between the X-ray and the radio properties, focusing on three orbital phases when an enhancement of the radio flux density has been detected, to test the link between the inflow (X-ray) and the outflow (radio jet) to/from the compact object. In two out of three cases we associate the presence of the radio jet to a spectral transition in the X-rays, although the transition does not precede the radio flare, as detected in other Z sources. An analogous behaviour has recently been found in the black hole candidate GX 339-4. In the third case, the radio light curve shows a similar shape to the X-ray light curve. We discuss our results in the context of jet models, considering also black hole candidates.Comment: Accepted for publication in MNRA

Methylation-capture and Next-Generation sequencing of free circulating DNA from human plasma

Background Free circulating DNA (fcDNA) has many potential clinical applications, due to the non-invasive way in which it is collected. However, because of the low concentration of fcDNA in blood, genome-wide analysis carries many technical challenges that must be overcome before fcDNA studies can reach their full potential. There are currently no definitive standards for fcDNA collection, processing and whole-genome sequencing. We report novel detailed methodology for the capture of high-quality methylated fcDNA, library preparation and downstream genome-wide Next-Generation Sequencing. We also describe the effects of sample storage, processing and scaling on fcDNA recovery and quality. Results Use of serum versus plasma, and storage of blood prior to separation resulted in genomic DNA contamination, likely due to leukocyte lysis. Methylated fcDNA fragments were isolated from 5 donors using a methyl-binding protein-based protocol and appear as a discrete band of ~180 bases. This discrete band allows minimal sample loss at the size restriction step in library preparation for Next-Generation Sequencing, allowing for high-quality sequencing from minimal amounts of fcDNA. Following sequencing, we obtained 37×106-86×106 unique mappable reads, representing more than 50% of total mappable reads. The methylation status of 9 genomic regions as determined by DNA capture and sequencing was independently validated by clonal bisulphite sequencing. Conclusions Our optimized methods provide high-quality methylated fcDNA suitable for whole-genome sequencing, and allow good library complexity and accurate sequencing, despite using less than half of the recommended minimum input DNA

Nucleotide identity and variability among different Pakistani hepatitis C virus isolates

<p>Abstract</p> <p>Background</p> <p>The variability within the hepatitis C virus (HCV) genome has formed the basis for several genotyping methods and used widely for HCV genotyping worldwide.</p> <p>Aim</p> <p>The aim of the present study was to determine percent nucleotide identity and variability in HCV isolates prevalent in different geographical regions of Pakistan.</p> <p>Methods</p> <p>Sequencing analysis of the 5'noncoding region (5'-NCR) of 100 HCV RNA-positive patients representing all the four provinces of Pakistan were carried out using ABI PRISM 3100 Genetic Analyzer.</p> <p>Results</p> <p>The results showed that type 3 is the predominant genotypes circulating in Pakistan, with an overall prevalence of 50%. Types 1 and 4 viruses were 9% and 6% respectively. The overall nucleotide similarity among different Pakistani isolates was 92.50% ± 0.50%. Pakistani isolates from different areas showed 7.5% ± 0.50% nucleotide variability in 5'NCR region. The percent nucleotide identity (PNI) was 98.11% ± 0.50% within Pakistani type 1 sequences, 98.10% ± 0.60% for type 3 sequences, and 99.80% ± 0.20% for type 4 sequences. The PNI between different genotypes was 93.90% ± 0.20% for type 1 and type 3, 94.80% ± 0.12% for type 1 and type 4, and 94.40% ± 0.22% for type 3 and type 4.</p> <p>Conclusion</p> <p>Genotype 3 is the most prevalent HCV genotype in Pakistan. Minimum and maximum percent nucleotide divergences were noted between genotype 1 and 4 and 1 and 3 respectively.</p

A Study of the Learnability of Relational Properties: Model Counting Meets Machine Learning (MCML)

This paper introduces the MCML approach for empirically studying the learnability of relational properties that can be expressed in the well-known software design language Alloy. A key novelty of MCML is quantification of the performance of and semantic differences among trained machine learning (ML) models, specifically decision trees, with respect to entire (bounded) input spaces, and not just for given training and test datasets (as is the common practice). MCML reduces the quantification problems to the classic complexity theory problem of model counting, and employs state-of-the-art model counters. The results show that relatively simple ML models can achieve surprisingly high performance (accuracy and F1-score) when evaluated in the common setting of using training and test datasets - even when the training dataset is much smaller than the test dataset - indicating the seeming simplicity of learning relational properties. However, MCML metrics based on model counting show that the performance can degrade substantially when tested against the entire (bounded) input space, indicating the high complexity of precisely learning these properties, and the usefulness of model counting in quantifying the true performance

Analogy-Making as a Core Primitive in the Software Engineering Toolbox

An analogy is an identification of structural similarities and correspondences between two objects. Computational models of analogy making have been studied extensively in the field of cognitive science to better understand high-level human cognition. For instance, Melanie Mitchell and Douglas Hofstadter sought to better understand high-level perception by developing the Copycat algorithm for completing analogies between letter sequences. In this paper, we argue that analogy making should be seen as a core primitive in software engineering. We motivate this argument by showing how complex software engineering problems such as program understanding and source-code transformation learning can be reduced to an instance of the analogy-making problem. We demonstrate this idea using Sifter, a new analogy-making algorithm suitable for software engineering applications that adapts and extends ideas from Copycat. In particular, Sifter reduces analogy-making to searching for a sequence of update rule applications. Sifter uses a novel representation for mathematical structures capable of effectively representing the wide variety of information embedded in software. We conclude by listing major areas of future work for Sifter and analogy-making in software engineering.Comment: Conference paper at SPLASH 'Onward!' 2020. Code is available at https://github.com/95616ARG/sifte

A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer

To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we compared the microsatellite instability (MSI) by the amplification of 10 microsatellite loci and immunohistochemical detection of hMSH2 and hMLH1 expression between the primary resected tumours and the secondary resected residual tumours after 5 or 6 courses of CDDP-based chemotherapy in the 24 cases of ovarian cancer. Of the 24 primary resected tumours, 9 (37.5%) showed MSI (7 cases of MSI-L, 2 cases of MSI-H), while 15 (72.5%) were microsatellite stable tumours (MSS). The primary tumours also had MSI in the residual tumours after CDDP-based chemotherapy. However, all of the cases with MSS in the primary resected tumours exhibited MSI (2 cases were MSI-L, and 13 cases were MSI-H) in the residual tumours after CDDP-based chemotherapy (P< 0.001). Furthermore, 11 (73.3%) of these cases which changed from MSS to MSI also had a change in the expression of hMLH1 from positive to undetectable (P< 0.001). Our data suggest that tumour MSI changes during CDDP-based chemotherapy, and that the loss of hMLH1 expression is one of the factors that has the greatest effect on this transformation. © 2001 Cancer Research Campaignhttp://www.bjcancer.co