Myofibroblasts are important contributors to human hepatocellular carcinoma: Evidence for tumor promotion by proteome profiling

Liver cancer typically occurs with a background of chronic fibrosis, characterized by the accumulation of myofibroblast‐like cells. We performed 2D‐PAGE‐based comparative analyses with the aim to identify proteins expressed in human hepatocellular carcinoma (HCC) tissue but not in neighboring healthy liver tissue, and to make out which cell types are responsible for the expression of proteins most characteristic for HCC. LC‐MS/MS analysis of the most striking spots identified proteins that were mainly related to myofibroblast‐like cells. To gain more insights into the role of these cells in their contribution to HCC, we isolated myofibroblast‐like cells as well as hepatocytes, both derived from HCC tissues, and subjected them to proteome profiling based on shotgun experiments. Comparative analysis, also referring to proteome profiles of other cell types previously investigated by us, pointed again to a marked contribution of myofibroblast‐like cells to HCC. Intriguingly, secretome analysis of these cells identified several growth factors that may act as tumor promoters and several proteins that have been described as potential biomarkers for HCC including dickkopf‐1, connective tissue growth factor, and CXCL1. Other biomarker candidates presently identified in the secretome of myofibroblasts, including lipocalin‐1 and pappalysin‐1, may be selected for future clinical validation. The identification of myofibroblast‐like cells as important source of tumor‐promoters may open new avenues to therapeutic intervention by targeting these stroma cells in addition to the cancer cells.     

Controlling Single Molecule Conductance by a Locally Induced Chemical Reaction on Individual Thiophene Units

Among the prerequisites for the progress of single‐molecule‐based electronic devices are a better understanding of the electronic properties at the individual molecular level and the development of methods to tune the charge transport through molecular junctions. Scanning tunneling microscopy (STM) is an ideal tool not only for the characterization, but also for the manipulation of single atoms and molecules on surfaces. The conductance through a single molecule can be measured by contacting the molecule with atomic precision and forming a molecular bridge between the metallic STM tip electrode and the metallic surface electrode. The parameters affecting the conductance are mainly related to their electronic structure and to the coupling to the metallic electrodes. Here, the experimental and theoretical analyses are focused on single tetracenothiophene molecules and demonstrate that an in situ‐induced direct desulfurization reaction of the thiophene moiety strongly improves the molecular anchoring by forming covalent bonds between molecular carbon and copper surface atoms. This bond formation leads to an increase of the conductance by about 50 % compared to the initial state.     

The magnitude and temperature dependence of the Kerr constant in liquid crystal blue phases and the dark conglomerate phase

A new method of evaluating the Kerr constant in liquid crystals (LCs) is used to determine the temperature dependence of the Kerr effect in blue phases I and II (BPI and BPII) and to investigate the Kerr constant of the isotropic dark conglomerate (DC) phase. This method employs relatively small driving voltages and a vertical field switching (VFS) device geometry. An unusually large Kerr constant, K, is determined in the BPs of a non-polymer-stabilised material, ～3×10^?9 mV^?2 (BPI). The large value of K is attributed to significant pre-transitional values of the dielectric anisotropy and birefringence. K follows an inverse dependence on temperature and we consequently suggest that BPI demonstrates properties best suited to electro-optic devices. The new methodology has the advantage of revealing the dispersion of K in a single measurement. It is also possible to deconvolute the influence of the Kerr effect from measurements of electrostriction of the BP lattice. Finally, the Kerr effect has been measured for the first time in the DC phase of an oxadiazole bent-core liquid crystalline material, and is found to take rather low values, ～1×10^?11 mV^?2, which can be understood in the context of the physical properties of the material.     

Mono-carboxylated diaminedichloridoplatinum(IV) complexes--selective synthesis, characterization, and cytotoxicity

(OC-6-43)-Dichlorido(N,N-dimethyl-ethane-1,2-diamine)dihydroxidoplatinum(IV) could selectively be mono-carboxylated with succinic anhydride based on the steric hindrance caused by the two methyl groups of the equatorial ligand. Subsequent esterification of the uncoordinated carboxylic acid with alcohols of different lengths (methanol, butanol, hexanol and octanol) afforded the corresponding esters. The synthesized complexes were characterized in detail by elemental analysis, ESI-MS, multinuclear ((1)H, (13)C, (15)N and (195)Pt) NMR spectroscopy and in two cases by X-ray crystallography. Cytotoxicity of novel platinum(IV) compounds was investigated in four human cancer cell lines (CH1, A549, SW480 and SK-OV-3). Remarkably, the most lipophilic complexes showed IC(50) values down to the low micromolar or even nanomolar range.     

Evolving a metabolic subsumption architecture for cooperative control of the e-puck

Subsumption architectures are a well-known model for behaviour-based robotic control. The global behaviour is achieved by defining a hierarchy of increasingly sophisticated behaviours. We are interested in using evolutionary algorithms to develop appropriate control architectures. We observe that the layered arrangement of behaviours in subsumption architectures are a significant obstacle to automating the development of control systems. We propose an alternative subsumption architecture inspired by the bacterial metabolism, that is more amenable to evolutionary development, in which communities of simple reactive agents combine in a stochastic process to confer appropriate behaviour on the robot. We evaluate this approach by developing a traditional and a metabolic solution to a simple control problem using a simulation of the e-puck educational robot. Additionally we show that behavioural strategies designed into the metabolic controller can also be optimised through artificial evolution.     

Talking about free groups in naturally enriched languages

The elementary theory of a non-commutative free group with a predicate for equality of length is proved hereditarily undecidable. This theory is shown to be ‘finitely axiomatizable’ modulo the second order stipulation that some centralizer be free cyclic. The theory of free groups in a weaker language using only a predecessor concept is investigated in the hope of shedding some light on Tarski's problems.     

Gold-Catalyzed C(sp2)−C(sp) Coupling by Alkynylation through Oxidative Addition of Bromoalkynes

A gold(I)-catalyzed cascade cyclization–alkynylation of allenoates using alkynyl bromide to generate β-alkynyl-γ-butenolides was investigated. Whereas alkynyl iodides afforded significant amounts of the homo-coupling of two lactone units, alkynyl bromides led to a selective reaction, and a broad functional group tolerance was observed. Under the optimized reaction conditions, it was possible to directly synthesize a large range of β-alkynyl-γ-butenolides in moderate to good yields without the need for any external oxidant.