Slider—maximum use of probability information for alignment of short sequence reads and SNP detection

Motivation: A plethora of alignment tools have been created that are designed to best fit different types of alignment conditions. While some of these are made for aligning Illumina Sequence Analyzer reads, none of these are fully utilizing its probability (prb) output. In this article, we will introduce a new alignment approach (Slider) that reduces the alignment problem space by utilizing each read base's probabilities given in the prb files

Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease

Copyright @ 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.Background: α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients. Methods: We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-γ. Results: Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child–Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child–Pugh A score and in 46% with a B or C score. Conclusion: These results suggest that anti-AFP Th1 responses are more likely to be present in patients who are in an early stage of disease (for both tumour stage and liver cirrhosis), whereas anti-AFP Tc1 responses are more likely to be present in patients with late-stage liver cirrhosis. Therefore, these data provide valuable information for the design of vaccination strategies against HCC.Association for International Cancer Research and Polkemmet Fund, London Clinic

Transferrin receptor 2 (TfR2) and HFE mutational analysis in non‐C282Y iron overload: identification of a novel TfR2 mutation

Blood. 2002 Aug 1;100(3):1075-7. Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation. Mattman A, Huntsman D, Lockitch G, Langlois S, Buskard N, Ralston D, Butterfield Y, Rodrigues P, Jones S, Porto G, Marra M, De Sousa M, Vatcher G. SourceGenes, Elements, and Metabolism Program, Children and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada. Abstract Hereditary hemochromatosis (HH) is classically associated with a Cys282Tyr (C282Y) mutation of the HFE gene. Non-C282Y HH is a heterogeneous group accounting for 15% of HH in Northern Europe. Pathogenic mutations of the transferrin receptor 2 (TfR2) gene have been identified in 4 Italian pedigrees with the latter syndrome. The goal of this study was to perform a mutational analysis of the TfR2 and HFE genes in a cohort of non-C282Y iron overload patients of mixed ethnic backgrounds. Several sequence variants were identified within the TfR2 gene, including a homozygous missense change in exon 17, c2069 A-->C, which changes a glutamine to a proline residue at position 690. This putative mutation was found in a severely affected Portuguese man and 2 family members with the same genotype. In summary, pathologic TfR2 mutations are present outside of Italy, accounting for a small proportion of non-C282Y HH

'The Brick' is not a brick : A comprehensive study of the structure and dynamics of the Central Molecular Zone cloud G0.253+0.016

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society.In this paper we provide a comprehensive description of the internal dynamics of G0.253+0.016 (a.k.a. 'the Brick'); one of the most massive and dense molecular clouds in the Galaxy to lack signatures of widespread star formation. As a potential host to a future generation of high-mass stars, understanding largely quiescent molecular clouds like G0.253+0.016 is of critical importance. In this paper, we reanalyse Atacama Large Millimeter Array cycle 0 HNCO $J=4(0,4)-3(0,3)$ data at 3 mm, using two new pieces of software which we make available to the community. First, scousepy, a Python implementation of the spectral line fitting algorithm scouse. Secondly, acorns (Agglomerative Clustering for ORganising Nested Structures), a hierarchical n-dimensional clustering algorithm designed for use with discrete spectroscopic data. Together, these tools provide an unbiased measurement of the line of sight velocity dispersion in this cloud, $\sigma_{v_{los}, {\rm 1D}}=4.4\pm2.1$ kms$^{-1}$, which is somewhat larger than predicted by velocity dispersion-size relations for the Central Molecular Zone (CMZ). The dispersion of centroid velocities in the plane of the sky are comparable, yielding $\sigma_{v_{los}, {\rm 1D}}/\sigma_{v_{pos}, {\rm 1D}}\sim1.2\pm0.3$. This isotropy may indicate that the line-of-sight extent of the cloud is approximately equivalent to that in the plane of the sky. Combining our kinematic decomposition with radiative transfer modelling we conclude that G0.253+0.016 is not a single, coherent, and centrally-condensed molecular cloud; 'the Brick' is not a \emph{brick}. Instead, G0.253+0.016 is a dynamically complex and hierarchically-structured molecular cloud whose morphology is consistent with the influence of the orbital dynamics and shear in the CMZ.Peer reviewedFinal Accepted Versio

The biodiversity benefit of native forests and mixed-species plantations over monoculture plantations

Aim: China's Grain for Green Program (GFGP) is the largest reforestation programme in the world and has been operating since 1999. The GFGP has promoted the establishment of tree plantations over the restoration of diverse native forests. In a previous study, we showed that native forests support a higher species richness and abundance of birds and bees than do GFGP plantations and that mixed-species GFGP plantations support a higher level of bird (but not bee) diversity than do any individual GFGP monocultures (although still below that of native forests). Here, we use metabarcoding of arthropod diversity to test the generality of these results. Location: Sichuan, China. Methods: We sampled arthropod communities using pan traps in the land cover types concerned under the GFGP. These land use types include croplands (the land cover being reforested under the GFGP), native forests (the reference ecosystem as the benchmark for the GFGP’s biodiversity effects) and the dominant GFGP reforestation outcomes: monoculture and mixed-species plantations. We used COI-amplicon sequencing (“metabarcoding”) of the arthropod samples to quantify and assess the arthropod community profiles associated with each land cover type. Results: Native forests support the highest overall levels of arthropod species diversity, followed by mixed-species plantations, followed by bamboo and other monocultures. Also, the arthropod community in native forests shares more species with mixed-species plantations than it does with any of the monocultures. Together, these results broadly corroborate our previous conclusions on birds and bees but show a higher arthropod biodiversity value of mixed-species plantations than previously indicated by bees alone. Main conclusion: In our previous study, we recommended that GFGP should prioritize the conservation and restoration of native forests. Also, where plantations are to be used, we recommended that the GFGP should promote mixed-species arrangements over monocultures. Both these recommendations should result in more effective protection of terrestrial biodiversity, which is an important objective of China's land-sustainability spending. The results of this study strengthen these recommendations because our policy prescriptions are now also based on a dataset that includes over 500 species-resolution taxa, ranging across the Arthropoda

Realism and Objectivism in Quantum Mechanics

The present study attempts to provide a consistent and coherent account of what the world could be like, given the conceptual framework and results of contemporary quantum theory. It is suggested that standard quantum mechanics can, and indeed should, be understood as a realist theory within its domain of application. It is pointed out, however, that a viable realist interpretation of quantum theory requires the abandonment or radical revision of the classical conception of physical reality and its traditional philosophical presuppositions. It is argued, in this direction, that the conceptualization of the nature of reality, as arising out of our most basic physical theory, calls for a kind of contextual realism. Within the domain of quantum mechanics, knowledge of 'reality in itself', 'the real such as it truly is' independent of the way it is contextualized, is impossible in principle. In this connection, the meaning of objectivity in quantum mechanics is analyzed, whilst the important question concerning the nature of quantum objects is explored.Comment: 20 pages. arXiv admin note: substantial text overlap with arXiv:0811.3696, arXiv:quant-ph/0502099, arXiv:0904.2702, arXiv:0904.2859, arXiv:0905.013

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

Kochen-Specker Vectors

We give a constructive and exhaustive definition of Kochen-Specker (KS) vectors in a Hilbert space of any dimension as well as of all the remaining vectors of the space. KS vectors are elements of any set of orthonormal states, i.e., vectors in n-dim Hilbert space, H^n, n>3 to which it is impossible to assign 1s and 0s in such a way that no two mutually orthogonal vectors from the set are both assigned 1 and that not all mutually orthogonal vectors are assigned 0. Our constructive definition of such KS vectors is based on algorithms that generate MMP diagrams corresponding to blocks of orthogonal vectors in R^n, on algorithms that single out those diagrams on which algebraic 0-1 states cannot be defined, and on algorithms that solve nonlinear equations describing the orthogonalities of the vectors by means of statistically polynomially complex interval analysis and self-teaching programs. The algorithms are limited neither by the number of dimensions nor by the number of vectors. To demonstrate the power of the algorithms, all 4-dim KS vector systems containing up to 24 vectors were generated and described, all 3-dim vector systems containing up to 30 vectors were scanned, and several general properties of KS vectors were found.Comment: 19 pages, 6 figures, title changed, introduction thoroughly rewritten, n-dim rotation of KS vectors defined, original Kochen-Specker 192 (117) vector system translated into MMP diagram notation with a new graphical representation, results on Tkadlec's dual diagrams added, several other new results added, journal version: to be published in J. Phys. A, 38 (2005). Web page: http://m3k.grad.hr/pavici

‘The Brick’ is not a brick: a comprehensive study of the structure and dynamics of the central molecular zone cloud G0.253+0.016

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society © 2019 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.In this paper we provide a comprehensive description of the internal dynamics of G0.253+0.016 (a.k.a. ‘the Brick’); one of the most massive and dense molecular clouds in the Galaxy to lack signatures of widespread star formation. As a potential host to a future generation of high-mass stars, understanding largely quiescent molecular clouds like G0.253+0.016 is of critical importance. In this paper, we reanalyse Atacama Large Millimeter Array cycle 0 HNCO J = 4(0, 4) − 3(0, 3) data at 3 mm, using two new pieces of software that we make available to the community. First, SCOUSEPY, a Python implementation of the spectral line fitting algorithm SCOUSE. Secondly, ACORNS (Agglomerative Clustering for ORganising Nested Structures), a hierarchical n-dimensional clustering algorithm designed for use with discrete spectroscopic data. Together, these tools provide an unbiased measurement of the line-of-sight velocity dispersion in this cloud, σvlos,1D=4.4±2.1 km s−1, which is somewhat larger than predicted by velocity dispersion-size relations for the central molecular zone (CMZ). The dispersion of centroid velocities in the plane of the sky are comparable, yielding σvlos,1D/σvpos,1D∼1.2±0.3⁠. This isotropy may indicate that the line-of-sight extent of the cloud is approximately equivalent to that in the plane of the sky. Combining our kinematic decomposition with radiative transfer modelling, we conclude that G0.253+0.016 is not a single, coherent, and centrally condensed molecular cloud; ‘the Brick’ is not a brick. Instead, G0.253+0.016 is a dynamically complex and hierarchically structured molecular cloud whose morphology is consistent with the influence of the orbital dynamics and shear in the CMZ

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation