Macromol. Biosci. 1/2013

Front Cover: Highly aligned 3D silk scaffolds using directional freezing in a custom designed chamber was demonstrated. The method is versatile and holds potential to produce complex, multicomponent aligned structures for various tissue engineering and biomedical applications, needing immediate cell alignment to mimic native tissue hierarchy and function. Further details can be found in the article by B. B. Mandal, E. S. Gil, B. Panilaitis, and D. L. Kaplan* on page 48 .

     

Self‐Organizing Alignment of Carbon Nanotubes in Thermoplastic Polyurethane

Summary: A simple compounding technique for the fabrication of polymer nanocomposites with single‐walled carbon nanotubes having exceptional alignment and improved mechanical properties is described. The aligned‐nanotube composite was prepared by dissolving single‐walled carbon nanotubes in a solution of thermoplastic polyurethane and tetrahydrofuran. Solvent‐polymer interactions that induce the orientation of soft chain segments during the swelling and moisture curing stage are believed to serve as a driving force for the macroscopic alignment of the carbon nanotubes.

Alignment of single‐walled carbon nanotubes in thermoplastic polyurethane during polar solvent exposure.     

Laminar Silk Scaffolds for Aligned Tissue Fabrication

3D‐biomaterial scaffolds with aligned architecture are of vital importance in tissue regeneration. A generic method is demonstrated to produce aligned biomaterial scaffolds using the physics of directional ice freezing. Homogeneously aligned 3D silk scaffolds with high porosity and alignment are prepared. The method can be adapted to a wide range of polymers and is devoid of any chemical reactions, thus avoiding potential complications associated with by‐products. Mechanical properties and cellular responses with chondrocytes and bone‐marrow‐derived hMSCs are studied, assessing survival, proliferation, and differentiation. In vivo tests suggest biocompatibility of the matrices for future tissue engineering applications, specifically in areas where high cellular alignment is needed.

     

Patterned Silk Film Scaffolds for Aligned Lamellar Bone Tissue Engineering

The alignment and osteogenic differentiation of MSCs on patterned silk films (PF) is investigated as a bottom‐up approach toward engineering bone lamellae. Screening PF with various groove dimensions shows that cell alignment is mediated by both the pattern width and depth. MSCs are differentiated in osteogenic medium for four weeks on flat films and on the PF that produce the best alignment. The PF support osteogenic differentiation while also inducing lamellar alignment of cells and matrix deposition. A secondary alignment effect is noted on the PF where a new layer of aligned cells grows over the first layer, but rotated obliquely to the underlying pattern. This layering and rotation of the MSCs resembles the cellular organization observed in native lamellar bone.

     

A novel fuzzy set based multifactor dimensionality reduction method for detecting gene–gene interaction

BackgroundGene-gene interaction (GGI) is one of the most popular approaches for finding the missing heritability of common complex traits in genetic association studies. The multifactor dimensionality reduction (MDR) method has been widely studied for detecting GGIs. In order to identify the best interaction model associated with disease susceptibility, MDR compares all possible genotype combinations in terms of their predictability of disease status from a simple binary high(H) and low(L) risk classification. However, this simple binary classification does not reflect the uncertainty of H/L classification.MethodsWe regard classifying H/L as equivalent to defining the degree of membership of two risk groups H/L. By adopting the fuzzy set theory, we propose Fuzzy MDR which takes into account the uncertainty of H/L classification. Fuzzy MDR allows the possibility of partial membership of H/L through a membership function which transforms the degree of uncertainty into a [0,1] scale. The best genotype combinations can be selected which maximizes a new fuzzy set based accuracy measure.ResultsTwo simulation studies are conducted to compare the power of the proposed Fuzzy MDR with that of MDR. Our results show that Fuzzy MDR has higher power than MDR. We illustrate the proposed Fuzzy MDR by analysing bipolar disorder (BD) trait of the WTCCC dataset to detect GGI associated with BD.ConclusionsWe propose a novel Fuzzy MDR method to detect gene–gene interaction by taking into account the uncertainly of H/L classification and show that it has higher power than MDR. Fuzzy MDR can be easily extended to handle continuous phenotypes as well. The program written in R for the proposed Fuzzy MDR is available at https://statgen.snu.ac.kr/software/FuzzyMDR.     

Embedding by pseudo atoms,and the topologically determined one-electronic energy levels

It is shown that the embedding of covalent clusters with the help of pseudo atoms and thefullerene electronic structure of amorphous carbon can be studied by the same formalism. Tight-binding model calculations were done for silicon clusters. It was found that the covalent clusters often have topologically determined energy levels that are cleared out from the spectrum in the presence of embedding.     

Synthesis and Alignment of Iron Oxide Nanoparticles in a Regenerated Cellulose Film

Summary: A polymer‐iron oxide nanocomposite film has been successfully synthesized by using a microporous regenerated cellulose film as template and aqueous ferrous chloride as precursor. The nanocomposite film was investigated with XRD, XPS, SEM, TEM, and VSM. The nanoparticles synthesized in situ were disk‐shaped with a mean diameter of ≈24 and thicknesses of 2.5–3.5 nm. For the first time, the nanodisks were well aligned in the cellulose matrix to form an ordered multibilayer structure by the shrinkage of the hybrid film while drying. The nanocomposite film displayed anisotropic magnetic properties as a result of the alignment of magnetic nanodisks. This work provides a novel and facile method for template synthesis of nanoparticles and aligned nanocomposites.

TEM image of the air‐dried nanocomposite film; slice perpendicular to the film plane.     

Classification of topologically chiral molecules

Graphs are partitioned into six classes from the perspective of chirality, depending on whether they are topologically achiral, whether there is at least one topologically achiral embedding, whether there is at least one rigidly achiral embedding, and whether there is at least one rigidly achiral presentation. Three of these classes are well represented by a variety of chemical structures: topologically chiral molecular graphs with no topologically achiral embeddings, topologically chiral molecular graphs with at least one rigidly achiral embedding, and topologically achiral molecular graphs with at least one rigidly achiral presentation. Known representatives of these three classes are described. Various meanings associated with the concepts molecular graph and intrinsic chirality are critically discussed. Previous arrangements of molecular graphs and molecules in a hierarchical order, ranging from the most to the least chiral, are interpreted in terms of the graph's and molecule's chiral persistence.     

Physical Continuity and Vertical Alignment of Block Copolymer Domains by Kinetically Controlled Electrospray Deposition

The fabrication of block copolymer (BCP) thin films is reported with vertically aligned cylindrical domains using continuous electrospray deposition onto bare wafer surfaces. The out‐of‐plane orientation of hexagonally packed styrene cylinders is achieved in the “fast‐wet” deposition regime in which rapid evaporation of the solvent in deposited droplets of polymer solution drives the vertical alignment of the self‐assembled structure. Thermally activated crosslinking of the polybutadiene matrix provides kinetic control of the morphology, freezing the vertical alignment and preventing relaxation of the system to its preferred parallel orientation on the nontreated substrate. Physically continuous vertically oriented domains can be achieved over several micrometers of film thickness. The ability of electrospray deposition to fabricate well‐ordered and aligned BCP films on nontreated substrates, the low amount of material used relative to spin‐coating, and the continuous nature of the deposition may open up new opportunities for BCP thin films.

     

Syntheses with heterocyclic β-enaminonitriles: An expeditious synthetic approach to polyfunctionally substituted 5-phenylsulfonylthiophenes and their fused derivatives

Summary Phenylsulfonylacetophenones1 react with a mixture of elemental sulfur and malononitrile to yield the corresponding 2-amino-4-aryl-5-phenylsulfonylthiophene-3-carbonitriles2. Compound2a could be annelated to the corresponding thieno[2,3-d]pyrimidine and thieno[2,3-c]-pyrazole derivatives3 and5 upon reaction with nitrogen nucleophiles (cyanamide and hydroxylamine hydrochloride), respectively. The applicability and synthetic potency of5 to develop a facile convenient route to the polyfunctionally substituted thieno[2,3:3,4]pyrazolo[1,5-a]pyrimidines8, 14, 17, 20, and21 is reported. Chemical and spectroscopic evidences for the structures of the new compounds are presented.

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Synthesen mit heterocyclischen -Enaminonitrilen: Ein rascher synthetischer Zugang zu polyfunktionell substituierten 5-Phenylsulfonylthiophenen und ihren kondensierten Derivaten

Zusammenfassung Die Phenylsulfonylacetophenone1 reagieren mit einem Gemisch aus elementarem Schwefel und Malonsäurenitril zu den entsprechenden 2-Amino-4-aryl-5-phenylsulfonylthiophen-3-carbonitrilen2. Durch Umsetzung mit Stickstoffnucleophilen wie Cyanamid und Hydroxylaminhydrochlorid konnten aus Verbindung2a die entsprechenden Thieno[2,3-d]pyrimidin- und Thieno[2,3-c]pyrazolderivate erhalten werden. Das synthetische Potential und die Anwendbarkeit von5 zur Synthese polyfunktionell substituierter Thieno[2,3:3,4]pyrazolo[1,5-a]pyrimidine (8,14,17,20,21) werden beschrieben. Die Strukturen der neuen Verbindungen wurden durch chemische und spektroskopische Methoden abgesichert.

     

Formation of Highly Aligned Collagen Nanofibers by Continuous Cyclic Stretch of a Collagen Hydrogel Sheet

A collagen sheet with highly aligned collagen fibers is fabricated by continuous cyclic stretch. The rearrangement of the collagen fibers depends on the different process parameters of the cyclic stretch, including magnitude, frequency, and period of stretch. The collagen fibers are aligned perpendicularly to the direction of the stretch. Corneal stromal cells and smooth muscle cells cultivated on the highly aligned collagen sheet show alignment along the collagen fibers without the stretch during culture. Thus, the sheet can be a suitable scaffold for use in regenerative medicine.

     

Gene network coherence based on prior knowledge using direct and indirect relationships

Gene networks (GNs) have become one of the most important approaches for modeling biological processes. They are very useful to understand the different complex biological processes that may occur in living organisms. Currently, one of the biggest challenge in any study related with GN is to assure the quality of these GNs. In this sense, recent works use artificial data sets or a direct comparison with prior biological knowledge. However, these approaches are not entirely accurate as they only take into account direct gene–gene interactions for validation, leaving aside the weak (indirect) relationships.We propose a new measure, named gene network coherence (GNC), to rate the coherence of an input network according to different biological databases. In this sense, the measure considers not only the direct gene–gene relationships but also the indirect ones to perform a complete and fairer evaluation of the input network. Hence, our approach is able to use the whole information stored in the networks. A GNC JAVA-based implementation is available at: http://fgomezvela.github.io/GNC/.The results achieved in this work show that GNC outperforms the classical approaches for assessing GNs by means of three different experiments using different biological databases and input networks. According to the results, we can conclude that the proposed measure, which considers the inherent information stored in the direct and indirect gene–gene relationships, offers a new robust solution to the problem of GNs biological validation.     

Development of a sugar-binding residue prediction system from protein sequences using support vector machine

Several methods have been proposed for protein–sugar binding site prediction using machine learning algorithms. However, they are not effective to learn various properties of binding site residues caused by various interactions between proteins and sugars. In this study, we classified sugars into acidic and nonacidic sugars and showed that their binding sites have different amino acid occurrence frequencies. By using this result, we developed sugar-binding residue predictors dedicated to the two classes of sugars: an acid sugar binding predictor and a nonacidic sugar binding predictor. We also developed a combination predictor which combines the results of the two predictors. We showed that when a sugar is known to be an acidic sugar, the acidic sugar binding predictor achieves the best performance, and showed that when a sugar is known to be a nonacidic sugar or is not known to be either of the two classes, the combination predictor achieves the best performance. Our method uses only amino acid sequences for prediction. Support vector machine was used as a machine learning algorithm and the position-specific scoring matrix created by the position-specific iterative basic local alignment search tool was used as the feature vector. We evaluated the performance of the predictors using five-fold cross-validation. We have launched our system, as an open source freeware tool on the GitHub repository (https://doi.org/10.5281/zenodo.61513).     

Well‐aligned Nano‐fiberous Membranes Based on Three‐pole Electrospinning with Channel Electrode

Three‐pole electrospinning devices integrated with a blade‐cage collector were developed to fabricate well‐aligned nano‐fiberous membranes. The proposed three‐pole configuration with a channel electrode can be a powerful tool in aligning nano‐fibers with regular diameter because the generated electric field can be accurately controlled without severe fluctuation in comparison with other methods. The three‐pole electrospinning method is also valid for industrial mass production and accurate diameter control of the aligned nano‐fibers.

     

Self‐Assembly of a Trinuclear Luminescent Europium Complex

Triangular luminescent box : Self‐assembly of a new multidentate receptor with europium cations results in the formation of trinuclear discrete complexes. X‐ray crystallography shows that nine‐coordinate cations are linked by ligands to provide a triangular complex in the solid state and in solution. Despite the coordinated solvent molecules, this topologically unusual complex exhibits remarkable luminescent properties.

     

Symmetry versus Minimal Pentagonal Adjacencies in Uranium‐Based Polyoxometalate Fullerene Topologies

C U soon : Clusters containing 60, 44, and 36 uranyl peroxide hydroxide polyhedra (see picture) adopt fullerene topologies of maximum symmetry. The largest of these, denoted U60, is topologically identical to C₆₀ with no pentagonal adjacencies and the highest possible symmetry. U44 adopts the topology with maximum symmetry rather than that with the lowest number of pentagonal adjacencies.

     

Effect of heating rate and γ-Radiation on the structure of As4SexTe6−x Glasses

The phenomena accompanying the temperature-induced structural changes in five As₄Se_xTe_6–x glasses, withx=1 tox=5, were examined and are discussed. Differential thermal analysis traces of each glass composition at different heating rates from 2 to 50 deg/min were obtained and interpreted. The effect of the Se/Te ratio on the crystallization behaviour is discussed. It is interesting to note that the compositional dependence of the overall behaviour of the crystallization activation energy (E) seems to be similar to that of both the melting point (T_m) and the thermal conductivity () for the investigated glasses. Created structural defects due to gamma-irradiation have some effects on the crystallization process.

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Zusammenfassung Die die temperaturbedingten strukturellen Veränderungen von 5 Glasern der allgemeinen Zusammensetzung As₄Se_xTe_6–x (x=1–5) begleitenden Phänomene wurden untersucht und diskutiert. Die von jedem Glas bei unterschiedlichen Aufheizgeschwindigkeiten zwischen 2 und 50 Grad pro Minute erhaltenen DTA-Kurven werden interpretiert. Der Effekt des Se/Te-Verhältnisses auf das Kristallisationsverhalten wird diskutiert. Von Interesse ist, daß die Abhängigkeit der Aktivierungsenergie (E) der Kristallisation von der Zusammensetzung der des Schmelzpunktes (Tm) und der Wärmeleitfähigkeit (*) der untersuchten Gläser ähnelt. Durch y-Bestrahlung hervorgerufene strukturelle Defekte haben einen gewissen Einfluß auf den Kristallisationsprozeß.

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, As₄Se_x,Te_6–x, c x=1–5. ( 2 50°/) . Se/Te . , , (T _m ) (). , -, .

     

Photocrosslinkable Liquid Crystal Main‐Chain Polymers: Thin Films and Electrospinning

For mechanical actuators, a response to external stimuli is required. Main‐chain liquid crystal elastomers (MCLCEs) show high response to changes in temperature especially in the vicinity of a phase transition. Most of these crosslinked materials were synthesized in a one‐step reaction which leads to a macroscopically aligned elastomer. Up to now only macroscopic samples have been prepared. We are presenting a new approach which allows us to prepare thin films as well as aligned fibers. First a liquid crystalline main‐chain polymer with a photoactive moiety was synthesized, which was oriented by a mechanical field and photocrosslinked. The thin films show exceptional mechanical properties such as large temperature‐dependent changes in length and a nonlinear stress–strain relation. To obtain fibers, we used the electrospinning process from solution with in situ UV curing. We obtained crosslinked fibers with a uniform alignment of the nematic director.

     

Noble Metal Decoration and Alignment of Carbon Nanotubes in Carboxymethyl Cellulose

A facile microwave method (MW) is described that accomplishes alignment and decoration of noble metals on carbon nanotubes (CNT) wrapped with carboxymethyl cellulose (CMC). Carbon nanotubes such as single‐ and multi‐walled, and Buckminsterfullerene (C‐60) are well dispersed using the sodium salt of CMC under sonication. Addition of respective noble metal salts then generates noble metal‐decorated CNT composites at room temperature. However, aligned nanocomposites of CNTs could only be generated by exposing the above nanocomposites to MW irradiation. The CNT composites are characterized using scanning electron microscopy, energy dispersive X‐ray analysis, X‐ray mapping, transmission electron microscopy, and UV‐visible spectroscopy. The general preparative procedure is versatile and provides a simple route to manufacturing useful metal‐coated CNT nanocomposites.