Multiply Folded Graphene

The folding of paper, hide, and woven fabric has been used for millennia to achieve enhanced articulation, curvature, and visual appeal for intrinsically flat, two-dimensional materials. For graphene, an ideal two-dimensional material, folding may transform it to complex shapes with new and distinct properties. Here, we present experimental results that folded structures in graphene, termed grafold, exist, and their formations can be controlled by introducing anisotropic surface curvature during graphene synthesis or transfer processes. Using pseudopotential-density functional theory calculations, we also show that double folding modifies the electronic band structure of graphene. Furthermore, we demonstrate the intercalation of C60 into the grafolds. Intercalation or functionalization of the chemically reactive folds further expands grafold's mechanical, chemical, optical, and electronic diversity.Comment: 29 pages, 10 figures (accepted in Phys. Rev. B

Src Binds Cortactin Through An Sh2 Domain Cystine-Mediated Linkage

Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions

Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids

We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity

A Polymorphic Variant of AFAP-110 Enhances cSrc Activity12

Enhanced expression and activity of cSrc are associated with ovarian cancer progression. Generally, cSrc does not contain acti- vating mutations; rather, its activity is increased in response to signals that affect a conformational change that releases its auto- inhibition. In this report, we analyzed ovarian cancer tissues for the expression of a cSrc-activating protein, AFAP-110. AFAP-110 activates cSrc through a direct interaction that releases it from its autoinhibited conformation. Immunohistochemical analysis re- vealed a concomitant increase of AFAP-110 and cSrc in ovarian cancer tissues. An analysis of the AFAP-110 coding sequence revealed the presence of a nonsynonymous, single-nucleotide polymorphism that resulted in a change of Ser403 to Cys403. In cells that express enhanced levels of cSrc, AFAP-110403C directed the activation of cSrc and the formation of podosomes indepen- dently of input signals, in contrast to wild-type AFAP-110. We therefore propose that, under conditions of cSrc overexpression, the polymorphic variant of AFAP-110 promotes cSrc activation. Further, these data indicate a mechanism by which an inherited genetic variation could influence ovarian cancer progression and could be used to predict the response to targeted therapy

Chemical Properties of Element 105 in Aqueous Solution: Halide Complex Formation and Anion Exchange into Triisoctyl Amine

Studies of the halide complexation of element 105 in aqueous solution were performed on 34-s 262Ha produced in the 249Bk(18-O,5n) reaction. The 262Ha was detected by measuring the fission and alpha activities associated with its decay and the alpha decays of its daughter, 4.3-s 258Lr. Time-correlated pairs of parent and daughter alpha particles provided a unique identification of the presence of 262Ha. About 1600 anion exchange separations of 262Ha from HCl and mixed HC1/HF solutions were performed on a one-minute time scale. Reversed-phase micro-chromatographic columns incorporating triisooctyl amine (TIOA) on an inert support were used in the computer-controlled liquid chromatography apparatus, ARCA II. 262Ha was shown to be adsorbed on the column from either 12 M HCl/0.02 M HF or 10 M HCl solutions like its homologs Nb and Ta, and like Pa. In elutions with 4 M HCl/0.02 M HF (Pa-Nb fraction), and with 6 M HNO3/O.OI5 M HF (Ta fraction), the 262Ha activity was found in the Pa-Nb fraction showing that the anionic halide complexes are different from those of Ta, and are more like those of Nb and Pa. In separate elutions with 10 M HCl/0.025 M HF (Pa fraction) and 6 M HN03/0.015 M HF (stripping of Nb) the 262Ha was found to be equally divided between the Pa and Nb fractions. The non-tantalum like halide complexation of Ha is indicative of the formation of oxohalide or hydroxohalide complexes, like [NbOCU]" and [PaOCl4] or [Pa(OH)2Cl4]", at least for intermediate HCl concentrations, in contrast to the pure halide complexes in Ta, like [TaCl6]-

Explanatory pluralism in the medical sciences: theory and practice

Explanatory pluralism is the view that the best form and level of explanation depends on the kind of question one seeks to answer by the explanation, and that in order to answer all questions in the best way possible, we need more than one form and level of explanation. In the first part of this article, we argue that explanatory pluralism holds for the medical sciences, at least in theory. However, in the second part of the article we show that medical research and practice is actually not fully and truly explanatory pluralist yet. Although the literature demonstrates a slowly growing interest in non-reductive explanations in medicine, the dominant approach in medicine is still methodologically reductionist. This implies that non-reductive explanations often do not get the attention they deserve. We argue that the field of medicine could benefit greatly by reconsidering its reductive tendencies and becoming fully and truly explanatory pluralist. Nonetheless, trying to achieve the right balance in the search for and application of reductive and non-reductive explanations will in any case be a difficult exercise

Microfluidic analysis techniques for safety assessment of pharmaceutical nano- and microsystems

This chapter reviews the evolution of microfabrication methods and materials, applicable to manufacturing of micro total analysis systems (or lab‐on‐a‐chip), from a general perspective. It discusses the possibilities and limitations associated with microfluidic cell culturing, or so called organ‐on‐a‐chip technology, together with selected examples of their exploitation to characterization of pharmaceutical nano‐ and microsystems. Materials selection plays a pivotal role in terms of ensuring the cell adhesion and viability as well as defining the prevailing culture conditions inside the microfluidic channels. The chapter focuses on the hepatic safety assessment of nanoparticles and gives an overview of the development of microfluidic immobilized enzyme reactors that could facilitate examination of the hepatic effects of nanomedicines under physiologically relevant conditions. It also provides an overview of the future prospects regarding system‐level integration possibilities facilitated by microfabrication of miniaturized separation and sample preparation systems as integral parts of microfluidic in vitro models.Non peer reviewe