Tuning the Properties of Ester-Based Degradable Polymers by Inserting Epoxides into Poly(ϵ-caprolactone)

A series of ester-ether copolymers were obtained via the reaction between α,ω-dihydroxyl poly(ϵ-caprolactone) (PCL) and ethylene oxide (EO) or monosubstituted epoxides catalyzed by strong phosphazene bases. The two types of monomeric units were distributed in highly random manners due to the concurrence of epoxide ring-opening and fast transesterification reactions. The substituent of epoxide showed an interesting bidirectional effect on the enzymatic degradability of the copolymer. Compared with PCL, copolymers derived from EO exhibited enhanced hydrophilicity and decreased crystallinity which then resulted in higher degradability. For the copolymers derived from propylene oxide and 1,2-butylene oxide, the hydrophobic alkyl pendant groups also allowed lower crystallinity of the copolymers thus higher degradation rates. However, further enlarging the pendant groups by using styrene oxide or 2-ethylhexyl glycidyl ether caused a decrease in the degradation rate, which might be ascribed to the higher bulkiness hindering the contact of ester groups with lipase.     

Facile Recoding of Selenocysteine in Nature

Selenocysteine (Sec or U) is encoded by UGA, a stop codon reassigned by a Sec‐specific elongation factor and a distinctive RNA structure. To discover possible code variations in extant organisms we analyzed 6.4 trillion base pairs of metagenomic sequences and 24 903 microbial genomes for tRNA^Sec species. As expected, UGA is the predominant Sec codon in use. We also found tRNA^Sec species that recognize the stop codons UAG and UAA, and ten sense codons. Selenoprotein synthesis programmed by UAG in Geodermatophilus and Blastococcus, and by the Cys codon UGU in Aeromonas salmonicida was confirmed by metabolic labeling with ⁷⁵Se or mass spectrometry. Other tRNA^Sec species with different anticodons enabled E. coli to synthesize active formate dehydrogenase H, a selenoenzyme. This illustrates the ease by which the genetic code may evolve new coding schemes, possibly aiding organisms to adapt to changing environments, and show the genetic code is much more flexible than previously thought.     

Random differences in Szemerédi’s theorem and related results

We extend the interior gradient estimate due to Korevaar-Simon for solutions of the mean curvature equation from the case of euclidean graphs to the general case of Killing graphs. Our main application is the proof of existence of Killing graphs with prescribed mean curvature function for continuous boundary data, thus extending a result due to Dajczer, Hinojosa, and Lira. In addition, we prove the existence and uniqueness of radial graphs in hyperbolic space with prescribed mean curvature function and asymptotic boundary data at infinity.     

Water solubility, antioxidant activity and cytochrome C binding of four families of exohedral adducts of C60 and C70

Over the past decade, surface-modified, water soluble fullerenes have been shown by many different investigators to exhibit strong antioxidant activity against reactive oxygen species (ROS) in vitro and to protect cells and tissues from oxidative injury and cell death in vivo. Nevertheless, progress in developing fullerenes as bona fide drug candidates has been hampered by three development issues: 1) lack of methods for scalable synthesis; 2) inability to produce highly purified, single-species regioisomers compatible with pharmaceutical applications; and 3) inadequate understanding of structure-function relationships with respect to various surface modifications (e.g., anionic versus cationic versus charge-neutral polarity). To address these challenges, we have designed and synthesized more than a dozen novel water soluble fullerenes that can be purified as single isomers and which we believe can be manufactured to scale at reasonable cost. These compounds differ in addition pattern, lipophilicity and number and type of charge and were examined for their water solubility, antioxidant activity against superoxide anions and binding of cytochrome C. Our results indicate that dendritic water soluble fullerene[60] monoadducts exhibit the highest degree of antioxidant activity against superoxide anions in vitro as compared with trismalonate-derived anionic fullerenes as well as cationic fullerenes of similar overall structure. Among the higher adducts, anionic derivatives have a higher antioxidant activity than comparable cationic compounds. To achieve sufficient water solubility without the aid of a surfactant or co-solvent at least three charges on the addends are required. Significantly, anionic in contrast to cationic fullerene adducts bind with high affinity to cytochrome C.     

Synthesis and solution behavior of carbon nanotubes decorated with amphiphilic block polyelectrolytes

The aqueous solubilization of carbon nanotubes (CNTs) with the aid of a block copolymer possessing one polyelectrolyte block (namely polystyrene-b-sodium (sulfamate/carboxylate polyisoprene)) is reported. The solubilization protocol, based on the co-dissolution of the copolymer and the CNTs, leads to the formation of supramolecular assemblies on the side walls of the tubes. Electron microscopy as well as infrared spectroscopy and thermogravimetric analysis were employed as meaningful probes to identify the adsorption of the polymer onto the surface of CNTs and the composition of the final hybrid material. Viscosity measurements on solutions of the copolymer decorated CNTs indicate that the polyelectrolyte effect, which is observed in the case of net polymers, is preserved in a lesser extent in the case of the copolymer/CNTs dispersions.     

Second SH3 domain of ponsin solved from powder diffraction

Determination of protein crystal structures is dependent on the growth of high-quality single crystals, a process that is not always successful. Optimum crystallization conditions must be systematically sought for, and microcrystalline powders are frequently obtained in failed attempts to grow the desired crystal. In materials science, structures of samples ranging from ceramics, pharmaceuticals, zeolites, etc., can nowadays be solved, almost routinely, from powdered samples, and there seems to be no fundamental reason, except the sheer size and complexity of the structures involved, why powder diffraction should not be employed to solve structures of small proteins. Indeed, recent work has shown that the high-quality powder diffraction data can be used in the study of protein crystal structures. We report the solution, model building, and refinement of a 67-residue protein domain crystal structure, with a cell volume of 64 879 A3, from powder diffraction. The second SH3 domain of ponsin, a protein of high biological significance due to its role in cellular processes, is determined and refined to resolution limits comparable to single-crystal techniques. Our results demonstrate the power and future applicability of the powder technique in structural biology.     

Bergman polynomials on an archipelago: Estimates, zeros and shape reconstruction

Growth estimates of complex orthogonal polynomials with respect to the area measure supported by a disjoint union of planar Jordan domains (called, in short, an archipelago) are obtained by a combination of methods of potential theory and rational approximation theory. The study of the asymptotic behavior of the roots of these polynomials reveals a surprisingly rich geometry, which reflects three characteristics: the relative position of an island in the archipelago, the analytic continuation picture of the Schwarz function of every individual boundary and the singular points of the exterior Green function. By way of explicit example, fine asymptotics are obtained for the lemniscate archipelago |z^m−1|<r^m, 0<r<1, which consists of m islands. The asymptotic analysis of the Christoffel functions associated to the same orthogonal polynomials leads to a very accurate reconstruction algorithm of the shape of the archipelago, knowing only finitely many of its power moments. This work naturally complements a 1969 study by H. Widom of Szegő orthogonal polynomials on an archipelago and the more recent asymptotic analysis of Bergman orthogonal polynomials unveiled by the last two authors and their collaborators.     

A Hardy field extension of Szemerédi's theorem

In 1975 Szemerédi proved that a set of integers of positive upper density contains arbitrarily long arithmetic progressions. Bergelson and Leibman showed in 1996 that the common difference of the arithmetic progression can be a square, a cube, or more generally of the form p(n) where p(n) is any integer polynomial with zero constant term. We produce a variety of new results of this type related to sequences that are not polynomial. We show that the common difference of the progression in Szemerédi's theorem can be of the form [nδ] where δ is any positive real number and [x] denotes the integer part of x. More generally, the common difference can be of the form [a(n)] where a(x) is any function that is a member of a Hardy field and satisfies a(x)/xk→∞ and a(x)/xk+1→0 for some non-negative integer k. The proof combines a new structural result for Hardy sequences, techniques from ergodic theory, and some recent equidistribution results of sequences on nilmanifolds.     

An argument-based approach to reasoning with clinical knowledge

Better use of biomedical knowledge is an increasingly pressing concern for tackling challenging diseases and for generally improving the quality of healthcare. The quantity of biomedical knowledge is enormous and it is rapidly increasing. Furthermore, in many areas it is incomplete and inconsistent. The development of techniques for representing and reasoning with biomedical knowledge is therefore a timely and potentially valuable goal. In this paper, we focus on an important and common type of biomedical knowledge that has been obtained from clinical trials and studies. We aim for (1) a simple language for representing the results of clinical trials and studies; (2) transparent reasoning with that knowledge that is intuitive and understandable to users; and (3) simple computation mechanisms with this knowledge in order to facilitate the development of viable implementations. Our approach is to propose a logical language that is tailored to the needs of representing and reasoning with the results of clinical trials and studies. Using this logical language, we generate arguments and counterarguments for the relative merits of treatments. In this way, the incompleteness and inconsistency in the knowledge is analysed via argumentation. In addition to motivating and formalising the logical and argumentation aspects of the framework, we provide algorithms and computational complexity results.