An algebraic description of screw dislocations in SC and BCC crystal lattices

We give an algebraic description of screw dislocations in a crystal, especially simple cubic (SC) and body centered cubic (BCC) crystals, using free abelian groups and fibering structures. We also show that the strain energy of a screw dislocation based on the spring model is expressed by the Epstein-Hurwitz zeta function approximately.Comment: 41 pages, 7 figure

Mobilization of arachidonic acid between diacyl and ether phospholipids in rabbit alveolar macrophages

AbstractThe metabolism of 20:4 (arachidonic acid) in alkenylacyl, alkylacyl and diacyl lipid classes in choline glycerophospholipids (CGP) and ethanolamine glycerophospholipids (EGP) in rabbit alveolar macrophages was examined. [3H]20:4 was very rapidly incorporated into diacyl glycerophosphocholine (GPC). After the removal of free 20:4, the radioactivity was gradually lost from diacyl GPC. Concomitantly, the radioactivities in alkylacyl GPC and alkenylacyl glycerophosphoethanolamine (GPE) were increased, indicating that 20:4 was mobilized from diacyl GPC to alkylacyl GPC and alkenylacyl GPE. The mobilization was considered to be a 20:4-specific event. The gradual accumulation of 20:4 in ether phospholipids leads to a high abundance of 20:4 in these lipids. These results suggest metabolic relationships between 20:4 and ether phospholipids, including platelet-activating factor (PAF)

Integrin Targeted Delivery of Gene Therapeutics

Integrins have become key targets for molecular imaging and for selective delivery of anti-cancer agents. Here we review recent work concerning the targeted delivery of antisense and siRNA oligonucleotides via integrins. A variety of approaches have been used to link oligonucleotides to ligands capable of binding integrins with high specificity and affinity. This includes direct chemical conjugation, incorporating oligonucleotides into lipoplexes, and use of various polymeric nanocarriers including dendrimers. The ligand-oligonucleotide conjugate or complex associates selectively with the integrin, followed by internalization into endosomes and trafficking through subcellular compartments. Escape of antisense or siRNA from the endosome to the cytosol and nucleus may come about through endogenous trafficking mechanisms, or because of membrane disrupting capabilities built into the conjugate or complex. Thus a variety of useful strategies are available for using integrins to enhance the pharmacological efficacy of therapeutic oligonucleotides

An O(n 1 2 +ɛ)-Space and Polynomial-Time Algorithm for Directed Planar Reachability

Abstract—We show that the reachability problem over directed planar graphs can be solved simultaneously in polynomial time and approximately O ( √ n) space. In contrast, the best space bound known for the reachability problem on general directed graphs with polynomial running time is O(n/2 √ log n Keywords-reachability, directed planar graph, sublinear space, polynomial time I

Epigenetic Landscape of Interacting Cells: A Model Simulation for Developmental Process

We propose a physical model for developmental process at cellular level to discuss the mechanism of epigenetic landscape. In our simplified model, a minimal model, the network of the interaction among cells generates the landscape epigenetically and the differentiation in developmental process is understood as a self-organization. The effect of the regulation by gene expression which is a key ingredient in development is renormalized into the interaction and the environment. At earlier stage of the development the energy landscape of the model is rugged with small amplitude. The state of cells in such a landscape is susceptible to fluctuations and not uniquely determined. These cells are regarded as stem cells. At later stage of the development the landscape has a funnel-like structure corresponding to the canalization in differentiation. The rewinding or stability of the differentiation is also demonstrated by substituting test cells into the time sequence of the model development.Comment: The discussion, in terms of our model, on the recently reported context-dependent behavior of STAP cells [Nature 505, 641-647 (2014)] has been added in Appendi

Cellular Uptake and Intracellular Trafficking of Antisense and siRNA Oligonucleotides

Significant progress is being made concerning the development of oligonucleotides as therapeutic agents. Studies with antisense, siRNA, and other forms of oligonucleotides have shown promise in cellular and animal models and in some clinical studies. Nonetheless our understanding of how oligonucleotides function in cells and tissues is really quite limited. One major issue concerns the modes of uptake and intracellular trafficking of oligonucleotides, whether as ‘free’ molecules, or linked to various delivery moieties such as nanoparticles or targeting ligands. In this review we examine the recent literature on oligonucleotide internalization and subcellular trafficking in the context of current insights into the basic machinery for endocytosis and intracellular vesicular traffic

The Chemistry and Biology of Oligonucleotide Conjugates

Short DNA or RNA oligonucleotides have tremendous potential as therapeutic agents. Because of their ability to engage in Watson-Crick base pairing they can interact with messenger mRNA or pre-mRNA targets with high selectivity and thus offer the possibility of precise manipulation of gene expression. This possibility has engendered extensive efforts to develop oligonucleotides as drugs, with many candidates already in clinical trials. However, a major impediment to the maturation of oligonucleotide-based therapeutics is the fact that these relatively large and usually highly charged molecules have great difficulty crossing cellular membranes and thus in penetrating to their sites of action in the cytosol or nucleus. In this Account we first summarize some basic aspects of the biology of antisense and siRNA oligonucleotides and then discuss chemical conjugation as an approach to improving the intracellular delivery and therapeutic potential of these agents. Our emphasis will be on the pharmacological ramifications of oligonucleotide conjugates rather than the details of conjugation chemistry. One important approach has been conjugation with ligands designed to bind to particular receptors and thus provide specificity to the interaction of cells with oligonucleotides. Another approach has been to couple antisense or siRNA with agents such as cell penetrating peptides that are designed to provoke escape of the conjugate from intracellular vesicular compartments. Both of these approaches have enjoyed some success. However, there remains much to be learned before oligonucleotide conjugates can find an important place in human therapeutics