175 research outputs found
A family case of fertile human 45,X,psu dic(15;Y) males
We report on a familial case including four male probands from three generations with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a female phenotype and only rarely with maleness, due to translocation of small Y chromosomal fragments to autosomes. These male patients are commonly infertile because of missing azoospermia factor regions from the Y long arm. In our familial case we found a pseudodicentric translocation chromosome, that contains almost the entire chromosomes 15 and Y. The translocation took place in an unknown male ancestor of our probands and has no apparent effect on fertility and phenotype of the carrier. FISH analysis demonstrated the deletion of the pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the nucleolus organizing region (NOR) from chromosome 15. The formation of the psu dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12) is as likely as the formation of Yqs. Nevertheless, it has not been described yet. This can be explained by the dicentricity of this translocation chromosome that usually leads to mitotic instability and meiotic imbalances. A second event, a stable inactivation of one of the two centromeres is obligatory to enable the transmission of the translocation chromosome and thus a stably reduced chromosome number from father to every son in this family
Cell shape analysis of random tessellations based on Minkowski tensors
To which degree are shape indices of individual cells of a tessellation
characteristic for the stochastic process that generates them? Within the
context of stochastic geometry and the physics of disordered materials, this
corresponds to the question of relationships between different stochastic
models. In the context of image analysis of synthetic and biological materials,
this question is central to the problem of inferring information about
formation processes from spatial measurements of resulting random structures.
We address this question by a theory-based simulation study of shape indices
derived from Minkowski tensors for a variety of tessellation models. We focus
on the relationship between two indices: an isoperimetric ratio of the
empirical averages of cell volume and area and the cell elongation quantified
by eigenvalue ratios of interfacial Minkowski tensors. Simulation data for
these quantities, as well as for distributions thereof and for correlations of
cell shape and volume, are presented for Voronoi mosaics of the Poisson point
process, determinantal and permanental point processes, and Gibbs hard-core and
random sequential absorption processes as well as for Laguerre tessellations of
polydisperse spheres and STIT- and Poisson hyperplane tessellations. These data
are complemented by mechanically stable crystalline sphere and disordered
ellipsoid packings and area-minimising foam models. We find that shape indices
of individual cells are not sufficient to unambiguously identify the generating
process even amongst this limited set of processes. However, we identify
significant differences of the shape indices between many of these tessellation
models. Given a realization of a tessellation, these shape indices can narrow
the choice of possible generating processes, providing a powerful tool which
can be further strengthened by density-resolved volume-shape correlations.Comment: Chapter of the forthcoming book "Tensor Valuations and their
Applications in Stochastic Geometry and Imaging" in Lecture Notes in
Mathematics edited by Markus Kiderlen and Eva B. Vedel Jense
The shared socioeconomic pathways and their energy, land use, and greenhouse gas emissions implications: An overview
This paper presents the overview of the Shared Socioeconomic Pathways (SSPs) and their energy, land use, and emissions implications. The SSPs are part of a new scenario framework, established by the climate change research community in order to facilitate the integrated analysis of future climate impacts, vulnerabilities, adaptation, and mitigation. The pathways were developed over the last years as a joint community effort and describe plausible major global developments that together would lead in the future to different challenges for mitigation and adaptation to climate change. The SSPs are based on five narratives describing alternative socio-economic developments, including sustainable development, regional rivalry, inequality, fossil-fueled development, and a middle-of-the-road development. The long-term demographic and economic projections of the SSPs depict a wide uncertainty range consistent with the scenario literature. A multi-model approach was used for the elaboration of the energy, land-use and the emissions trajectories of SSP-based scenarios. The baseline scenarios lead to global energy consumption of 500-1100 EJ in 2100, and feature vastly different land-use dynamics, ranging from a possible reduction in cropland area up to a massive expansion by more than 700 million hectares by 2100. The associated annual CO2 emissions of the baseline scenarios range from about 25 GtCO2 to more than 120 GtCO2 per year by 2100. With respect to mitigation, we find that associated costs strongly depend on three factors: 1) the policy assumptions, 2) the socio-economic narrative, and 3) the stringency of the target. The carbon price for reaching the target of 2.6 W/m2 differs in our analysis thus by about a factor of three across the SSP scenarios. Moreover, many models could not reach this target from the SSPs with high mitigation challenges. While the SSPs were designed to represent different mitigation and adaptation challenges, the resulting narratives and quantifications span a wide range of different futures broadly representative of the current literature. This allows their subsequent use and development in new assessments and research projects. Critical next steps for the community scenario process will, among others, involve regional and sectorial extensions, further elaboration of the adaptation and impacts dimension, as well as employing the SSP scenarios with the new generation of earth system models as part of the 6th climate model intercomparison project (CMIP6)
AO-10-IBER-16 - Ground based radiation field simulation of the MATROSHKA experiment: Physical and Biological Experiments for Radiation Risk Assessment - PART II
Enhanced anti-HIV-1 activity of G-quadruplexes comprising locked nucleic acids and intercalating nucleic acids
Two G-quadruplex forming sequences, 5âČ-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating nucleic acid, TINA). Incorporation of LNA or INA/TINA monomers provide as much as 8-fold improvement of anti-HIV-1 activity. We demonstrate for the first time a detailed analysis of the effect the incorporation of INA/TINA monomers in quadruplex forming oligonucleotides (QFOs) and the effect of LNA monomers in the context of biologically active QFOs. In addition, recent literature reports and our own studies on the gel retardation of the phosphodiester analogue of T30177 led to the conclusion that this sequence forms a parallel, dimeric G-quadruplex. Introduction of the 5âČ-phosphate inhibits dimerisation of this G-quadruplex as a result of negative chargeâcharge repulsion. Contrary to that, we found that attachment of the 5âČ-O-DMT-group produced a more active 17-mer sequence that showed signs of aggregationâforming multimeric G-quadruplex species in solution. Many of the antiviral QFOs in the present study formed more thermally stable G-quadruplexes and also high-order G-quadruplex structures which might be responsible for the increased antiviral activity observed
Abel Symposia
Discrete Morse theory has recently lead to new developments in the theory of random geometric complexes. This article surveys the methods and results obtained with this new approach, and discusses some of its shortcomings. It uses simulations to illustrate the results and to form conjectures, getting numerical estimates for combinatorial, topological, and geometric properties of weighted and unweighted Delaunay mosaics, their dual Voronoi tessellations, and the Alpha and Wrap complexes contained in the mosaics
p53 Gene Repair with Zinc Finger Nucleases Optimised by Yeast 1-Hybrid and Validated by Solexa Sequencing
The tumor suppressor gene p53 is mutated or deleted in over 50% of human tumors. As functional p53 plays a pivotal role in protecting against cancer development, several strategies for restoring wild-type (wt) p53 function have been investigated. In this study, we applied an approach using gene repair with zinc finger nucleases (ZFNs). We adapted a commercially-available yeast one-hybrid (Y1H) selection kit to allow rapid building and optimization of 4-finger constructs from randomized PCR libraries. We thus generated novel functional zinc finger nucleases against two DNA sites in the human p53 gene, near cancer mutation âhotspotsâ. The ZFNs were first validated using in vitro cleavage assays and in vivo episomal gene repair assays in HEK293T cells. Subsequently, the ZFNs were used to restore wt-p53 status in the SF268 human cancer cell line, via ZFN-induced homologous recombination. The frequency of gene repair and mutation by non-homologous end-joining was then ascertained in several cancer cell lines, using a deep sequencing strategy. Our Y1H system facilitates the generation and optimisation of novel, sequence-specific four- to six-finger peptides, and the p53-specific ZFN described here can be used to mutate or repair p53 in genomic loci
Computational Lipidology: Predicting Lipoprotein Density Profiles in Human Blood Plasma
Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond âbadâ and âgoodâ cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL), we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile) is calculated. As our main results, we (i) successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii) assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS), revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii) present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia
Abstracts of presentations on plant protection issues at the fifth international Mango Symposium Abstracts of presentations on plant protection issues at the Xth international congress of Virology: September 1-6, 1996 Dan Panorama Hotel, Tel Aviv, Israel August 11-16, 1996 Binyanei haoma, Jerusalem, Israel
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