126 research outputs found

    (2-Hydroxy­phenyl­imido-κN)(methano­lato-κO)[2-(2-oxidobenzyl­ideneamino)phenolato-κ2 O,N,O′](triphenyl­phosphine-κP)rhenium(V)

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    In the neutral title compound, [Re(C6H5NO)(C13H9NO2)(CH3O)(C18H15P)], an 18-valence-electron complex, the ReV ion lies in an octa­hedral coordination geometry with the tridentate dianionic Schiff base 2-(2-oxidobenzyl­idene­amino)phenolate ligand occupying three equatorial coordination sites, and with the triphenyl­phosphine ligand situated trans to the imine N atom. The ReV coordination is completed with a methano­late ligand and a 2-hydroxy­phenyl­imido(2-) ligand. There are two molecules in the asymmetric unit. The crystal structure involves O—H⋯O and C—H⋯O hydrogen bonds. One N and one C atom are disordered over two positions; the site occupancy factors are ca 0.7 and 0.3

    A polynomial bound for untangling geometric planar graphs

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    To untangle a geometric graph means to move some of the vertices so that the resulting geometric graph has no crossings. Pach and Tardos [Discrete Comput. Geom., 2002] asked if every n-vertex geometric planar graph can be untangled while keeping at least n^\epsilon vertices fixed. We answer this question in the affirmative with \epsilon=1/4. The previous best known bound was \Omega((\log n / \log\log n)^{1/2}). We also consider untangling geometric trees. It is known that every n-vertex geometric tree can be untangled while keeping at least (n/3)^{1/2} vertices fixed, while the best upper bound was O(n\log n)^{2/3}. We answer a question of Spillner and Wolff [arXiv:0709.0170 2007] by closing this gap for untangling trees. In particular, we show that for infinitely many values of n, there is an n-vertex geometric tree that cannot be untangled while keeping more than 3(n^{1/2}-1) vertices fixed. Moreover, we improve the lower bound to (n/2)^{1/2}.Comment: 14 pages, 7 figure

    Microbial expression systems for membrane proteins

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    Despite many high-profile successes, recombinant membrane protein production remains a technical challenge; it is still the case that many fewer membrane protein structures have been published than those of soluble proteins. However, progress is being made because empirical methods have been developed to produce the required quantity and quality of these challenging targets. This review focuses on the microbial expression systems that are a key source of recombinant prokaryotic and eukaryotic membrane proteins for structural studies. We provide an overview of the host strains, tags and promoters that, in our experience, are most likely to yield protein suitable for structural and functional characterization. We also catalogue the detergents used for solubilization and crystallization studies of these proteins. Here, we emphasize a combination of practical methods, not necessarily high-throughput, which can be implemented in any laboratory equipped for recombinant DNA technology and microbial cell culture

    Assessment of pre-clinical liver models based on their ability to predict the liver-tropism of AAV vectors

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    The liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors (rAAV). Multiple clinical trials have been undertaken for this target in the past 15 years, however we are still to see market approval of the first liver-targeted AAV-based gene therapy. Inefficient expression of the therapeutic transgene, vector-induced liver toxicity and capsid, and/or transgene-mediated immune responses reported at high vector doses are the main challenges to date. One of the contributing factors to the insufficient clinical outcomes, despite highly encouraging preclinical data, is the lack of robust, biologically- and clinically-predictive preclinical models. To this end, this study reports findings of a functional evaluation of six AAV vectors in twelve preclinical models of the human liver, with the aim to uncover which combination of models is the most relevant for the identification of AAV capsid variant for safe and efficient transgene delivery to primary human hepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepatocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses of each system. This should allow the development of novel gene therapies targeting the human liver

    Activation of PyMT in β Cells Induces Irreversible Hyperplasia, but Oncogene-Dependent Acinar Cell Carcinomas When Activated in Pancreatic Progenitors

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    It is unclear whether the cellular origin of various forms of pancreatic cancer involves transformation or transdifferentiation of different target cells or whether tumors arise from common precursors, with tumor types determined by the specific genetic alterations. Previous studies suggested that pancreatic ductal carcinomas might be induced by polyoma middle T antigen (PyMT) expressed in non-ductal cells. To ask whether PyMT transforms and transdifferentiates endocrine cells toward exocrine tumor phenotypes, we generated transgenic mice that carry tetracycline-inducible PyMT and a linked luciferase reporter. Induction of PyMT in β cells causes β-cell hyperplastic lesions that do not progress to malignant neoplasms. When PyMT is de-induced, β cell proliferation and growth cease; however, regression does not occur, suggesting that continued production of PyMT is not required to maintain the viable expanded β cell population. In contrast, induction of PyMT in early pancreatic progenitor cells under the control of Pdx1 produces acinar cell carcinomas and β-cell hyperplasia. The survival of acinar tumor cells is dependent on continued expression of PyMT. Our findings indicate that PyMT can induce exocrine tumors from pancreatic progenitor cells, but cells in the β cell lineage are not transdifferentiated toward exocrine cell types by PyMT; instead, they undergo oncogene-dependent hyperplastic growth, but do not require PyMT for survival

    Linear Extensions and Comparable Pairs in Partial Orders

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    We study the number of linear extensions of a partial order with a given proportion of comparable pairs of elements, and estimate the maximum and minimum possible numbers. We also show that a random interval partial order on nn elements has close to a third of the pairs comparable with high probability, and the number of linear extensions is n!2Θ(n)n! \, 2^{-\Theta(n)} with high probability
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