Modulation of Living Cell Behavior with Ultra‐Low Fouling Polymer Brush Interfaces

Ultra‐low fouling and functionalizable coatings represent emerging surface platforms for various analytical and biomedical applications such as those involving examination of cellular interactions in their native environments. Ultra‐low fouling surface platforms as advanced interfaces enabling modulation of behavior of living cells via tuning surface physicochemical properties are presented and studied. The state‐of‐art ultra‐low fouling surface‐grafted polymer brushes of zwitterionic poly(carboxybetaine acrylamide), nonionic poly(N‐(2‐hydroxypropyl)methacrylamide), and random copolymers of carboxybetaine methacrylamide (CBMAA) and HPMAA [p(CBMAA‐co‐HPMAA)] with tunable molar contents of CBMAA and HPMAA are employed. Using a model Huh7 cell line, a systematic study of surface wettability, swelling, and charge effects on the cell growth, shape, and cytoskeleton distribution is performed. This study reveals that ultra‐low fouling interfaces with a high content of zwitterionic moieties (>65 mol%) modulate cell behavior in a distinctly different way compared to coatings with a high content of nonionic HPMAA. These differences are attributed mostly to the surface hydration capabilities. The results demonstrate a high potential of carboxybetaine‐rich ultra‐low fouling surfaces with high hydration capabilities and minimum background signal interferences to create next‐generation bioresponsive interfaces for advanced studies of living objects.     

A new approach to construction of isoindolo[1,2-a]isoquinoline alkaloids Nuevamine, Jamtine, and Hirsutine via IMDAF reaction

The interaction between 1-furyl-1,2,3,4-tetrahydroisoquinolines and unsaturated acids derivatives (acryloyl, methacryloyl, and crotonoyl chloride, maleic and citraconic anhydride) was studied. It was shown that the reaction proceeds via amide formation and subsequent intramolecular Diels-Alder reaction of the furan (IMDAF). The [4+2] cycloaddition proceeded under mild reaction conditions (25-80 °C) and afforded only the exo-adduct in a high yield. With this method, a new approach to the isoindolo[1,2-a]isoquinoline system, the basic structural element of alkaloids Jamtine, Hirsutine, and Nuevamine, is proposed.     

Direct assembly of polyarenes via C-C coupling Using PIFA/BF3·Et2O

Direct oxidative Kita-type coupling between naphthalene and substituted benzenes was found to proceed via four-component coupling, leading to a linear tetraarene with a binaphthalene core. The methodology was extendable to the coupling of unfunctionalized 1,1'-binaphthalene with mesitylene to give a linear hexaarene product in a remarkably chemoselective manner in 87% yield. The method represents an attractive alternative to the traditional syntheses of related oligonaphthalene products via a sequence of metal-catalyzed cross-coupling steps.     

Identification and specificity profiling of protein prenyltransferase inhibitors using new fluorescent phosphoisoprenoids

Posttranslational modification of proteins with farnesyl and geranylgeranyl isoprenoids is a widespread phenomenon in eukaryotic organisms. Isoprenylation is conferred by three protein prenyltransferases: farnesyl transferase (FTase), geranylgeranyl transferase type-I (GGTase-I), and Rab geranylgeranyltransferase (RabGGTase). Inhibitors of these enzymes have emerged as promising therapeutic compounds for treatment of cancer, viral and parasite originated diseases, as well as osteoporosis. However, no generic nonradioactive protein prenyltransferase assay has been reported to date, complicating identification of enzyme-specific inhibitors. We have addressed this issue by developing two fluorescent analogues of farnesyl and geranylgeranyl pyrophosphates {3,7-dimethyl-8-(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-octa-2,6-diene-1}pyrophosphate (NBD-GPP) and {3,7,11-trimethyl-12-(7-nitro-benzo[1,2,5]oxadiazo-4-ylamino)-dodeca-2,6,10-trien-1} pyrophosphate (NBD-FPP), respectively. We demonstrate that these compounds can serve as efficient lipid donors for prenyltransferases. Using these fluorescent lipids, we have developed two simple (SDS-PAGE and bead-based) in vitro prenylation assays applicable to all prenyltransferases. Using the SDS-PAGE assay, we found that, in contrast to previous reports, the tyrosine phosphatase PRL-3 may possibly be a dual substrate for both FTase and GGTase-I. The on-bead prenylation assay was used to identify prenyltransferase inhibitors that displayed nanomolar affinity for RabGGTase and FTase. Detailed analysis of the two inhibitors revealed a complex inhibition mechanism in which their association with the peptide binding site of the enzyme reduces the enzyme's affinity for lipid and peptide substrates without competing directly with their binding. Finally, we demonstrate that the developed fluorescent isoprenoids can directly and efficiently penetrate into mammalian cells and be incorporated in vivo into small GTPases.     

Frank–Condon principle and adjustment of optical waveguides with nonhomogeneous refractive indices

The adjustment of two different selfocs is considered using both exact formulas for the mode-connection coefficients expressed in terms of Hermite polynomials of several variables and a qualitative approach based on the Frank–Condon principle. Several examples of the refractive-index dependence are studied and illustrative plots for these examples are presented. The connection with the tomographic approach to quantum states of a two-dimensional oscillator and the Frank–Condon factors is established.     

Decomposing Graphs into Long Paths

It is known that the edge set of a 2-edge-connected 3-regular graph can be decomposed into paths of length 3. W. Li asked whether the edge set of every 2-edge-connected graph can be decomposed into paths of length at least 3. The graphs C ₃, C ₄, C ₅, and K ₄−e have no such decompositions. We construct an infinite sequence {F _i } _i=0 ^∞ of nondecomposable graphs. On the other hand, we prove that every other 2-edge-connected graph has a desired decomposition. This revised version was published online in June 2006 with corrections to the Cover Date.     

Topological Model Categories Generated by Finite Complexes

 Our main result states that for each finite complex L the category TOP of topological spaces possesses a model category structure (in the sense of Quillen) whose weak equivalences are precisely maps which induce isomorphisms of all [L]-homotopy groups. The concept of [L]-homotopy has earlier been introduced by the first author and is based on Dranishnikov’s notion of extension dimension. As a corollary we obtain an algebraic characterization of [L]-homotopy equivalences between [L]-complexes. This result extends two classical theorems of J. H. C. Whitehead. One of them – describing homotopy equivalences between CW-complexes as maps inducing isomorphisms of all homotopy groups – is obtained by letting L = {point}. The other – describing n-homotopy equivalences between at most (n+1)-dimensional CW-complexes as maps inducing isomorphisms of k-dimensional homotopy groups with k ⩽ n – by letting L = S ⁿ⁺¹ , n ⩾ 0.     

A fast algorithm for equitable coloring

A proper vertex coloring of a graph is equitable if the sizes of color classes differ by at most one. The celebrated Hajnal-Szemerédi Theorem states: For every positive integer r, every graph with maximum degree at most r has an equitable coloring with r+1 colors. We show that this coloring can be obtained in O(rn ²) time, where n is the number of vertices.     

Ore-type conditions implying 2-factors consisting of short cycles

For every graph G, let . The main result of the paper says that every n-vertex graph G with contains each spanning subgraph H all whose components are isomorphic to graphs in . This generalizes the earlier results of Justesen, Enomoto, and Wang, and is a step towards an Ore-type analogue of the Bollobás-Eldridge-Catlin Conjecture.