16,212 research outputs found

    Pollen morphology of four succulent species of Euphorbia (Euphorbiaceae)

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    The pol l en morphology of four succul ent spec i es of Euphorbia L. from the IvoFy Coast (E. ingens, E. kamerunica , E. milii and E. unispina ) , were stud ied for the first time using light and scann i ng electron microscopy . In general the pol l en i s isopol ar , oblate spheroidal, medium size , t ricolpora te. Exine columel late , character is tic of angiosperms pollen . Differences in pol l en characters between taxa were observed. Exine and aperture features are recognized here as practica! taxonomic use in the delimi tation of taxa. Based on the exine structure two types of pollen are recogni zed¡ tectate perforate and microreticul ate. Intraspecifc va riat i on was encountered.La morfología pol ínica de cuatro especies sucul entas de l género Euphorbia L. de Costa de Marfi l (E. ingens, E. kamerunica, E. milii y E. unispina) , fue estudiada por primera vez utilizando microscopía óptica y el ectrónica de barri do . En general, el pol en es isopolar, oblongoes f eroi dal , de tamaño mediano, tric'olporado . Exina con colume l as , característi co del pol en de angi ospermas. Se observaron diferencias en l os caracteres polini ces dentro de los taxones. Las caracterí sticas de la exina y de sus aperturas son reconocidas como caracteres taxonómicos en la delimitación de las especies . Basándose en la estructura de la exina se pudieron di stinguir dos tipos de polen: tectado- perforado y mi croperforado . Se encontró variaci ón intraespecífic

    Phyolin: Identifying a Linear Perfect Phylogeny in Single-Cell DNA Sequencing Data of Tumors

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    Cancer arises from an evolutionary process where somatic mutations occur and eventually give rise to clonal expansions. Modeling this evolutionary process as a phylogeny is useful for treatment decision-making as well as understanding evolutionary patterns across patients and cancer types. However, cancer phylogeny inference from single-cell DNA sequencing data of tumors is challenging due to limitations with sequencing technology and the complexity of the resulting problem. Therefore, as a first step some value might be obtained from correctly classifying the evolutionary process as either linear or branched. The biological implications of these two high-level patterns are different and understanding what cancer types and which patients have each of these trajectories could provide useful insight for both clinicians and researchers. Here, we introduce the Linear Perfect Phylogeny Flipping Problem as a means of testing a null model that the tree topology is linear and show that it is NP-hard. We develop Phyolin and, through both in silico experiments and real data application, show that it is an accurate, easy to use and a reasonably fast method for classifying an evolutionary trajectory as linear or branched

    Panel 9: Problem Framing: Emerging Issues in DSS Research

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    Decision support systems (DSS) are commonly understood to be interactive computer-based systems that are designed to help managers cope with ill-defined situations. In the past, most DSSs have helped decision makers deal with issues that have been relatively easy to structure. These have not always been the issues that have been of most interest to them. This panel will address various research issues related to isolating and structuring the problems in which effective problem framing accounts for a large part of the performance variance in problem solving. While the members of the panel agree that DSS must be extended in order to help managers formulate problems, they differ in their perceptions of the criticality of issues to be considered. Joyce Elam is convinced that initial research efforts should be directed toward methods and feasibility of supporting decision makers in the task of framing multiple problem representations. She believes that ill-defined situations require creative problem formulations. In other words, asking the right questions can be more important than answering them. She has found that problem formulation appears to grow in importance as the need for alternative solutions increases. She will argue that the key to creative thinking in ill-defined situations is the manager\u27s ability to develop and explore alternative problem formulations and that DSS must facilitate this process. Omar El Sawy believes that successful problem framing is critically dependent on initially enlarging the problem space through effective environmental scanning and multiple scenario generation, similar to what is practiced in futures research. He will discuss the features of DSS that have divergent rather than convergent support capabilities and are suitable for problem framing. He will address the types of DSS capabilities and underlying technologies that can be used to support How about? and What else? as well as the more traditional What if? Benn Konsynski\u27s position is that research into problem-framing DSS must begin with an investigation of dialogue management. He will propose an approach that begins by exploring the human computer dialogue through which decision makers frame problems. Convinced that, for the most part, DSS dialogues are static and offer little help in structuring problems, he will discuss the proper apportionment of the cognitive responsibilities between manager and system. Charles Stabell suggests that, in order to develop more effective support for problem framing, we need to have a better understanding of how managers frame problems. In particular, he believes that to develop active support for problem framing, we need to consider and understand under what conditions, in what context, and for what purpose a manager might choose to use such a tool. He will address the issue by reviewing some ongoing research on key determinants of problem framing. In particular, he will discuss the operational code approach to studying managerial choice behavior; the approach considers the manager\u27s fundamental beliefs about life in organizations, the role of managers, and the basis for effective decision making. Sue Weber believes that we can best help managers frame problems in ill-structured situations by providing them with pattern- matching tools. These tools would help a manager gradually to accumulate patterns, extract the invariant features from these patterns, and map patterns and relations. Recognizing and then accepting a new problem formulation often requires considerable time and practice. Consequently, she calls for a problem-framing DSS that would support a manager in storing, retrieving, and modifying different mappings over many sessions until understanding and confidence in the formulation is developed

    Vitamin H-regulated transgene expression in mammalian cells

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    Although adjustable transgene expression systems are considered essential for future therapeutic and biopharmaceutical manufacturing applications, the currently available transcription control modalities all require side-effect-prone inducers such as immunosupressants, hormones and antibiotics for fine-tuning. We have designed a novel mammalian transcription-control system, which is reversibly fine-tuned by non-toxic vitamin H (also referred to as biotin). Ligation of vitamin H, by engineered Escherichia coli biotin ligase (BirA), to a synthetic biotinylation signal fused to the tetracycline-dependent transactivator (tTA), enables heterodimerization of tTA to a streptavidin-linked transrepressor domain (KRAB), thereby abolishing tTA-mediated transactivation of specific target promoters. As heterodimerization of tTA to KRAB is ultimately conditional upon the presence of vitamin H, the system is vitamin H responsive. Transgenic Chinese hamster ovary cells, engineered for vitamin H-responsive gene expression, showed high-level, adjustable and reversible production of a human model glycoprotein in bench-scale culture systems, bioreactor-based biopharmaceutical manufacturing scenarios, and after implantation into mice. The vitamin H-responsive expression systems showed unique band pass filter-like regulation features characterized by high-level expression at low (0-2 nM biotin), maximum repression at intermediate (100-1000 nM biotin), and high-level expression at increased (>100 000 nM biotin) biotin concentrations. Sequential ON-to-OFF-to-ON, ON-to-OFF and OFF-to-ON expression profiles with graded expression transitions can all be achieved by simply increasing the level of a single inducer molecule without exchanging the culture medium. These novel expression characteristics mediated by an FDA-licensed inducer may foster advances in therapeutic cell engineering and manufacturing of difficult-to-produce protein therapeutic

    Vitamin H-regulated transgene expression in mammalian cells

    Get PDF
    Although adjustable transgene expression systems are considered essential for future therapeutic and biopharmaceutical manufacturing applications, the currently available transcription control modalities all require side-effect-prone inducers such as immunosupressants, hormones and antibiotics for fine-tuning. We have designed a novel mammalian transcription-control system, which is reversibly fine-tuned by non-toxic vitamin H (also referred to as biotin). Ligation of vitamin H, by engineered Escherichia coli biotin ligase (BirA), to a synthetic biotinylation signal fused to the tetracycline-dependent transactivator (tTA), enables heterodimerization of tTA to a streptavidin-linked transrepressor domain (KRAB), thereby abolishing tTA-mediated transactivation of specific target promoters. As heterodimerization of tTA to KRAB is ultimately conditional upon the presence of vitamin H, the system is vitamin H responsive. Transgenic Chinese hamster ovary cells, engineered for vitamin H-responsive gene expression, showed high-level, adjustable and reversible production of a human model glycoprotein in bench-scale culture systems, bioreactor-based biopharmaceutical manufacturing scenarios, and after implantation into mice. The vitamin H-responsive expression systems showed unique band pass filter-like regulation features characterized by high-level expression at low (0–2 nM biotin), maximum repression at intermediate (100–1000 nM biotin), and high-level expression at increased (>100 000 nM biotin) biotin concentrations. Sequential ON-to-OFF-to-ON, ON-to-OFF and OFF-to-ON expression profiles with graded expression transitions can all be achieved by simply increasing the level of a single inducer molecule without exchanging the culture medium. These novel expression characteristics mediated by an FDA-licensed inducer may foster advances in therapeutic cell engineering and manufacturing of difficult-to-produce protein therapeutics

    Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions

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    The integrin heterodimer CD11b/CD18 (alpha M beta 2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive! and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet alpha llb beta 3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac,mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro,indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs

    A novel mammalian expression system derived from components coordinating nicotine degradation in arthrobacter nicotinovorans pAO1

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    We describe the design and detailed characterization of 6-hydroxy-nicotine (6HNic)-adjustable transgene expression (NICE) systems engineered for lentiviral transduction and in vivo modulation of angiogenic responses. Arthrobacter nicotinovorans pAO1 encodes a unique catabolic machinery on its plasmid pAO1, which enables this Gram-positive soil bacterium to use the tobacco alkaloid nicotine as the exclusive carbon source. The 6HNic-responsive repressor-operator (HdnoR-ONIC) interaction, controlling 6HNic oxidase production in A.nicotinovorans pAO1, was engineered for generic 6HNic-adjustable transgene expression in mammalian cells. HdnoR fused to different transactivation domains retained its ONIC-binding capacity in mammalian cells and reversibly adjusted transgene transcription from chimeric ONIC-containing promoters (PNIC; ONIC fused to a minimal eukaryotic promoter [Pmin]) in a 6HNic-responsive manner. The combination of transactivators containing various transactivation domains with promoters differing in the number of operator modules as well as in their relative inter-ONIC and/or ONIC-Pmin spacing revealed steric constraints influencing overall NICE regulation performance in mammalian cells. Mice implanted with microencapsulated cells engineered for NICE-controlled expression of the human glycoprotein secreted placental alkaline phosphatase (SEAP) showed high SEAP serum levels in the absence of regulating 6HNic. 6HNic was unable to modulate SEAP expression, suggesting that this nicotine derivative exhibits control-incompatible pharmacokinetics in mice. However, chicken embryos transduced with HIV-1-derived self-inactivating lentiviral particles transgenic for NICE-adjustable expression of the human vascular endothelial growth factor 121 (VEGF121) showed graded 6HNic response following administration of different 6HNic concentrations. Owing to the clinically inert and highly water-soluble compound 6HNic, NICE-adjustable transgene control systems may become a welcome alternative to available drug-responsive homologs in basic research, therapeutic cell engineering and biopharmaceutical manufacturin

    Scoping the evolution of corporate social responsibility (CSR) research in the sustainable development goals (SDGS) era

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    © 2020 by the authors. Amidst a contemporary culture of climate awareness, unprecedented levels of transparency and visibility are forcing industrial organizations to broaden their value chains and deepen the impacts of Corporate Social Responsibility (CSR) initiatives. While it may be common knowledge that the 2030 agenda cannot be achieved on a business-as-usual trajectory, this study seeks to determine to what ends the United Nations Sustainable Development Goals (SDGs) have impacted CSR research. Highlighting linkages and interdependencies between the SDGs and evolution of CSR practice, this paper analyzes a final sample of 56 relevant journal articles from the period 2015-2020. With the intent of bridging policy and practice, thematic coding analysis has supported the identification and interpretation of key emergent research themes. Using threedescriptive categorical classifications (i.e., single-dimension, bi-combination of dimensions, sustainability dimension), the results of this paper provide an in-depth discussion into strategic community, company, consumer, investor, and employee foci. Furthermore, the analysis provides a timely and descriptive overview of how CSR research has approached the SDGs and which ones are being prioritized. By deepening the understanding of potential synergies between business strategy, global climate agendas and the common good, this paper contributes to an increased comprehension of how CSR and financial performance can be improved over the long-term

    The Complexity of Recognizing Geometric Hypergraphs

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    As set systems, hypergraphs are omnipresent and have various representations ranging from Euler and Venn diagrams to contact representations. In a geometric representation of a hypergraph H=(V,E)H=(V,E), each vertex vVv\in V is associated with a point pvRdp_v\in \mathbb{R}^d and each hyperedge eEe\in E is associated with a connected set seRds_e\subset \mathbb{R}^d such that {pvvV}se={pvve}\{p_v\mid v\in V\}\cap s_e=\{p_v\mid v\in e\} for all eEe\in E. We say that a given hypergraph HH is representable by some (infinite) family FF of sets in Rd\mathbb{R}^d, if there exist PRdP\subset \mathbb{R}^d and SFS \subseteq F such that (P,S)(P,S) is a geometric representation of HH. For a family F, we define RECOGNITION(F) as the problem to determine if a given hypergraph is representable by F. It is known that the RECOGNITION problem is R\exists\mathbb{R}-hard for halfspaces in Rd\mathbb{R}^d. We study the families of translates of balls and ellipsoids in Rd\mathbb{R}^d, as well as of other convex sets, and show that their RECOGNITION problems are also R\exists\mathbb{R}-complete. This means that these recognition problems are equivalent to deciding whether a multivariate system of polynomial equations with integer coefficients has a real solution.Comment: Appears in the Proceedings of the 31st International Symposium on Graph Drawing and Network Visualization (GD 2023) 17 pages, 11 figure

    A novel mammalian expression system derived from components coordinating nicotine degradation in arthrobacter nicotinovorans pAO1

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    We describe the design and detailed characterization of 6-hydroxy-nicotine (6HNic)-adjustable transgene expression (NICE) systems engineered for lentiviral transduction and in vivo modulation of angiogenic responses. Arthrobacter nicotinovorans pAO1 encodes a unique catabolic machinery on its plasmid pAO1, which enables this Gram-positive soil bacterium to use the tobacco alkaloid nicotine as the exclusive carbon source. The 6HNic-responsive repressor-operator (HdnoR-O(NIC)) interaction, controlling 6HNic oxidase production in A.nicotinovorans pAO1, was engineered for generic 6HNic-adjustable transgene expression in mammalian cells. HdnoR fused to different transactivation domains retained its O(NIC)-binding capacity in mammalian cells and reversibly adjusted transgene transcription from chimeric O(NIC)-containing promoters (P(NIC); O(NIC) fused to a minimal eukaryotic promoter [P(min)]) in a 6HNic-responsive manner. The combination of transactivators containing various transactivation domains with promoters differing in the number of operator modules as well as in their relative inter-O(NIC) and/or O(NIC)-P(min) spacing revealed steric constraints influencing overall NICE regulation performance in mammalian cells. Mice implanted with microencapsulated cells engineered for NICE-controlled expression of the human glycoprotein secreted placental alkaline phosphatase (SEAP) showed high SEAP serum levels in the absence of regulating 6HNic. 6HNic was unable to modulate SEAP expression, suggesting that this nicotine derivative exhibits control-incompatible pharmacokinetics in mice. However, chicken embryos transduced with HIV-1-derived self-inactivating lentiviral particles transgenic for NICE-adjustable expression of the human vascular endothelial growth factor 121 (VEGF(121)) showed graded 6HNic response following administration of different 6HNic concentrations. Owing to the clinically inert and highly water-soluble compound 6HNic, NICE-adjustable transgene control systems may become a welcome alternative to available drug-responsive homologs in basic research, therapeutic cell engineering and biopharmaceutical manufacturing
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