Hydrogen-bonded diketopyrrolopyrrole (DPP) pigments as organic semiconductors

Diketopyrrolopyrroles (DPPs) have recently gained attention as building-blocks for organic semiconducting polymers and small molecules, however the semiconducting properties of their hydrogen-bonded (H-bonded) pigment forms have not been explored. Herein we report on the performance of three archetypical H-bonded DPP pigments, which show ambipolar carrier mobilities in the range 0.01–0.06 cm²/V s in organic field-effect transistors. Their semiconducting properties are correlated with crystal structure, where an H-bonded crystal lattice supports close and relatively cofacial π–π stacking. To better understand transport in these systems, density functional theory calculations were carried out, indicating theoretical maximum ambipolar mobility values of ∼0.3 cm²/V s. Based on these experimental and theoretical results, H-bonded DPPs represent a viable alternative to more established DPP-containing polymers and small molecules where H-bonding is blocked by N-alkylation.     

Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.     

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted chemical and biological destructive effects, and functional activity improvement. This approach is of special importance in biomedicine, since this makes it possible to reduce the limitations of drug delivery related to the toxicity and side effects of therapeutics, their low bioavailability and biocompatibility. This review highlights current progress in the use of lipid systems to deliver active substances to the human body. Various lipid compositions modified with amphiphilic open-chain and macrocyclic compounds, peptide molecules and alternative target ligands are discussed. Liposome modification also evolves by creating new hybrid structures consisting of organic and inorganic parts. Such nanohybrid platforms include cerasomes, which are considered as alternative nanocarriers allowing to reduce inherent limitations of lipid nanoparticles. Compositions based on mesoporous silica are beginning to acquire no less relevance due to their unique features, such as advanced porous properties, well-proven drug delivery efficiency and their versatility for creating highly efficient nanomaterials. The types of silica nanoparticles, their efficacy in biomedical applications and hybrid inorganic-polymer platforms are the subject of discussion in this review, with current challenges emphasized.     

A nonlinear galerkin method: The two-level fourier-collocation case

In this article we study the implementation of the Nonlinear Galerkin method as a multiresolution method when a two-level Fourier-collocation discretization is used. The set of collocation points with an even number of points is considered as the fine grid and decomposed into two coarse grids containing half as many points. Using these two grids we decompose the unknown into the sum of a large scale component containing only low frequency modes and based on one of the coarse grids and a small scale component containing only high frequency modes and based on the other coarse grid. This produces interesting connections between the physical space and the Fourier space representations of the function. A nonlinear Galerkin scheme is then applied to the Burgers equation; finally, implementation issues are discussed showing the advantages of the method.     

The role of transforming growth factor-beta1, -beta2, and -beta3 in androgen-responsive growth of NRP-152 rat prostatic epithelial cells

Proacrosin, the zymogen form of the serine protease beta-acrosin, is thought to function as a secondary binding molecule between mammalian gametes during fertilization (Jansen et al., 1995: Int J Dev Biol 39, 501-510). The interaction involves strong ionic bonds between positively charged amino acids on proacrosin and negatively charged polysulphate groups on zona pellucida glycoproteins. In this investigation, we identified the basic residues on proacrosin that are important for this binding. Site-directed mutagenesis shows that two groups of amino acids comprising His47, Arg50, and Arg51 together with Arg250, Lys252, and Arg253 are crucial because their deletion or replacement severely reduces affinity for zona glycoproteins. Molecular models of proacrosin reveal that these residues are located along one face of the protein on two exposed surface loops that project over and around the catalytic site. These findings support the hypothesis that polysulphate binding sites on proacrosin are formed by a restricted number of basic amino acids on the surface of the protein, presenting a specific orientation that is complementary to negatively charged sulphate groups on zona glycoproteins. Identification and elucidation of the stereochemistry of these charged moieties will aid design of new kinds of nonsteroidal antifertility agents.     

Automatic generation of visual programming environments

We have developed the visual language compiler-compiler (VLCC) system to automatically generate visual programming environments. VLCC is a grammar based system that can support implementation of any visual language by assisting the language designer in defining the language's graphical objects, syntax, and semantics. The final result of the generation process includes an integrated environment with a visual editor and a compiler for the defined visual language. In VLCC, graphical tools define visual languages to create both graphical objects and composition rules. Visual editors enable language designers to directly and visually manipulate the syntax of these languages. To capture the widest range of visual languages, the VLCC system can be configured for a specific language class. Different language classes can be characterized depending on their graphical objects' structure and on the way they can be composed. Also, box and arrow diagrams are defined for primitive objects with attaching points and for composition rules to join boxes and arrows at those attaching points. After choosing the visual language type to create, the designer can concentrate on language definition details. VLCC uses the positional grammar model as its underlying grammar formalism     

The relationship between advisors and students

Considering the influence of graduation courses on the scientific productivity in Brazil, fifty productive Brazilian scientists working in life sciences were interviewed about their relationship with their advisors and their own experience with their students. Admired by freedom and intellectual qualities, by their love and dedication for science, advisors seem to have had a deep influence on their students. This bond is not free from either an idealized frame or from some complaints and conflicts. Interviewed scientists see in themselves lesser qualities and faults but the same respect for freedom. Some students are thought to be specially important to the interviewed's productivity. Eldest and most productive scientists seem to be intellectually more impressed by their advisors than the other groups. The emotional and sometimes strong and idealized bond between advisor and students lead us to believe that the stated frequencies of conflicts might be underestimated.     

Bifurcations in the mechanics of hypoelastic composite materials

This paper analyses the modification of a hypoelastic material behavior at the small variations of the material parameters, using elements of the bifurcation theory. The considered material is obtained by the combination of two granular hypoelastic materials, which have the memory of the initial stress state, and their stress work depends on stress history. Its constitutive equation is deduced by means of the constitutive equations of the component materials. In consequence, mechanical properties of those two materials are interpenetrated, generating, for the new material, domains of stability, as well as surfaces in stress space, surfaces on which the strain–stress system is not invertible. It results that it is necessary to choose correctly the component materials, their share and the process of forming the new material, so that the imposed solicitation by the operation conditions should be accessible to a composite material. When we are modelling, the choice of the component materials means the choice of their constitutive equations—the share of the component materials will fix the stability domain of the composite material—the forming process chosen correctly will determine that the initial stress state (from which the loading path will start) should be in the stability domain of the material.     

First-principles approach to the calculation of electronic spectra in clusters

We discuss a method for first-principles calculations of photoemission spectra in small clusters, going well beyond a standard density functional theory-local density approximation (DFT-LDA) approach. Starting with a DFT-LDA calculation, we evaluate self-energy contributions to the quasiparticle energies of an electron or hole in the GW scheme, where the self-energy Σ = GW is constructed from the one-particle Green's function G and the RPA screened Coulomb interaction W. The contributions of structural relaxation are taken into account. We show the importance of these effects at the example of the photoemission spectrum of SiH₄. We also briefly discuss results for longer hydrogenated silicon chains, and address the problem of optical absorption.