Patterning of light-emitting conjugated polymer nanofibres

Organic materials have revolutionized optoelectronics by their processability, flexibility and low cost, with application to light-emitting devices for full-colour screens, solar cells and lasers. Some low-dimensional organic semiconductor structures exhibit properties resembling those of inorganics, such as polarized emission and enhanced electroluminescence. One-dimensional metallic, III-V and II-VI nanostructures have also been the subject of intense investigation as building blocks for nanoelectronics and photonics. Given that one-dimensional polymer nanostructures, such as polymer nanofibres, are compatible with sub-micrometre patterning capability and electromagnetic confinement within subwavelength volumes, they can offer the benefits of organic light sources to nanoscale optics. Here we report on the optical properties of fully conjugated, electrospun polymer nanofibres. We assess their waveguiding performance and emission tuneability in the whole visible range. We demonstrate the enhancement of the fibre forward emission through imprinting periodic nanostructures using room-temperature nanoimprint lithography, and investigate the angular dispersion of differently polarized emitted light.     

Small-molecule inhibitors of PDK1

Signal transduction of many growth factors and oncogenes is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1), a master regulator of a number of downstream signal protein kinase cascades. Hence, PDK1 represents a convergence point for receptor tyrosine kinase and cytokine-mediated pathways for the regulation of vital cell processes such as cell survival and proliferation. Pathological upregulation of PDK1 signalling due to constitutive growth factor receptor activation and/or PTEN (phosphatase and tensin homologue) mutations significantly triggers downstream signalling, e.g. PKB/Akt, which subsequently promote proliferative events such as tumour invasiveness, angiogenesis, and progression. Consistent with this, a mouse model expressing low levels of PDK1 is protected from tumourigenesis resulting from loss of PTEN. Because more than 50 % of all human cancers possess significant overstimulation of the PDK1 signalling pathway, inhibition of this protein kinase by small molecules is predicted to result in effective inhibition of cancer cell proliferation and thus be therapeutically beneficial. Various classes of small-molecule PDK1 inhibitors have been published in patents and papers. Herein we present for the first time a comprehensive collection of small molecules reported to interact with PDK1, and we refer to their biological characterisation in terms of activity and selectivity for PDK1.     

Rapid depletion of marbofloxacin residues in rabbit after therapeutic treatment

Although rabbit meat production represents a very small percentage of the world meat market, this percentage has been growing continuously during the last 30 years. Rabbit is considered a minor food species, and therefore no drugs are specifically registered for this animal. This situation encourages rabbit farmers to make off-label use of antibacterial drugs authorized for food-producing animal species other than rabbits. In the present study, the distribution and elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a representative of a new generation of antibacterial drugs active against most gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and has short elimination times in bovine and swine species. Rabbits were treated with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual concentrations in liver, kidney, and muscle tissues were determined posttreatment with high-performance liquid chromatography and fluorescence detection. Marbofloxacin was rapidly distributed and eliminated from rabbit tissues. Concentrations were higher in the liver and kidney than in muscle. However, 48 h after the end of treatment, marbofloxacin concentrations dropped below the maximum residue level fixed for this antibacterial drug in cattle and pigs. Considering the efficacy of marbofloxacin for the treatment of the most common rabbit diseases, its tolerability, and its short elimination time as verified in the present study, use of this antibacterial drug could be extended to therapeutic treatment of rabbits.     

Optimal design and seismic performance of Multi‐Tuned Mass Damper Inerter (MTMDI) applied to adjacent high‐rise buildings

The tuned mass damper inerter (TMDI) is an enhanced variant of the tuned mass damper (TMD) that benefits from the mass‐amplification effect of the inerter. Here, a multi‐TMDI (MTMDI) system (comprising more than one TMDI) linking two adjacent high‐rise buildings is presented as an unconventional seismic protection strategy. The relative acceleration response of the adjacent structures triggers large reaction forces of the inerter devices in the MTMDI, which in turn efficiently improve the seismic performance of the two buildings. By addressing a real project of two adjacent high‐rise buildings connected by two corridors equipped with the proposed MTMDI system, the displacement‐, interstory drift‐, and acceleration‐based parametric optimizations are separately performed by employing Nondominated Sorting Genetic Algorithm II (NSGA‐II) under 44 ground motions from the FEMA P695 far‐field record set. It is found that the frequency content of the seismic input has strong impact on the MTMDI mitigation performance. Adopting realistic mass ratio constraints, the optimally designed MTMDI outperforms both conventional MTMD and single TMDI in acceleration control, while it is not much effective in mitigating the displacement response due to the highly flexible nature of the high‐rise buildings, in contrast to other literature studies generally focused on low‐to‐medium rise buildings.     

Spike detection and clustering with unsupervised wavelet optimization in extracellular neural recordings

Automatic and accurate detection of action potentials of unknown waveforms in noisy extracellular neural recordings is an important requirement for developing brain-computer interfaces. This study introduces a new, wavelet-based manifestation variable that combines the wavelet shrinkage denoising with multiscale edge detection for robustly detecting and finding the occurrence time of action potentials in noisy signals. To further improve the detection performance by eliminating the dependence of the method to the choice of the mother wavelet, we propose an unsupervised optimization for best basis selection. Moreover, another unsupervised criterion based on a correlation similarity measure was defined to update the wavelet selection during the clustering to improve the spike sorting performance. The proposed method was compared to several previously proposed methods by using a wide range of realistic simulated data as well as selected experimental recordings of intracortical signals from freely moving rats. The detection performance of the proposed method substantially surpassed previous methods for all signals tested. Moreover, updating the wavelet selection for the clustering task was shown to improve the classification performance with respect to maintaining the same wavelet as for the detection stage.     

Human monoclonal antibodies to domain C of tenascin-C selectively target solid tumors in vivo

We had previously reported that splice isoforms of tenascin-C containing the extra-domain C are virtually absent in normal adult tissues but are highly abundant in high-grade astrocytomas, with a prominent peri-vascular pattern of expression. We now report that the extra-domain C of tenascin-C is strongly expressed in the majority of lung cancers, with a vascular and stromal pattern of expression. Using antibody phage technology, we have generated a human monoclonal antibody (G11), with a dissociation constant K(D) = 4.2 nM for the human domain C. The G11 antibody, expressed in scFv and in mini-antibody (SIP) format, as well as a scFv-interleukin-2 fusion protein, was then characterized in quantitative biodistribution studies using mice grafted subcutaneously with U87 gliomas, revealing a selective tumor uptake, with tumor/blood ratios up to 11.8:1 at 24 h. A radioiodinated preparation of SIP(G11) was also investigated in a double tracer study using an orthotopic rat glioma model, confirming the antibody's ability to preferentially localize at the tumor site, with tumor/brain ratios superior to the ones observed with (18)F-fluorodeoxyglucose. These tumor-targeting properties, together with the strong immunohistochemical staining of human tumor sections, indicate that the G11 antibody may be used as a portable targeting moiety for the selective delivery of imaging and therapeutic agents to gliomas and lung tumors.     

A finite element model for describing the effect of muscle shortening on surface EMG

A finite-element model for the generation of single fiber action potentials in a muscle undergoing various degrees of fiber shortening is developed. The muscle is assumed fusiform with muscle fibers following a curvilinear path described by a Gaussian function. Different degrees of fiber shortening are simulated by changing the parameters of the fiber path and maintaining the volume of the muscle constant. The conductivity tensor is adapted to the muscle fiber orientation. In each point of the volume conductor, the conductivity of the muscle tissue in the direction of the fiber is larger than that in the transversal direction. Thus, the conductivity tensor changes point-by-point with fiber shortening, adapting to the fiber paths. An analytical derivation of the conductivity tensor is provided. The volume conductor is then studied with a finite-element approach using the analytically derived conductivity tensor. Representative simulations of single fiber action potentials with the muscle at different degrees of shortening are presented. It is shown that the geometrical changes in the muscle, which imply changes in the conductivity tensor, determine important variations in action potential shape, thus affecting its amplitude and frequency content. The model provides a new tool for interpreting surface EMG signal features with changes in muscle geometry, as it happens during dynamic contractions.     

Identification of protein ubiquitylation by electrospray ionization tandem mass spectrometric analysis of sulfonated tryptic peptides

We report here the application of electrospray ionization tandem mass spectrometry for the characterization of protein ubiquitylation, an important posttranslational modification of cellular proteins. Trypsin digestion of ubiquitin-conjugated proteins produces diglycine branched peptides containing the modification sites. Chemical derivatization by N-terminal sulfonation was carried out on several model peptides for the formation of a characteristic fragmentation pattern in their MS/MS analysis. The fragmentation of derivatized singly charged peptides results in a product ion distribution similar to that already observed by MALDI-TOF MS/MS. Signature fragments distinguished the diglycine branched peptides from other modified and unmodified peptides, while the sequencing product ions reveal the amino acid sequence and the location of the ubiquitylation site. Doubly charged peptide derivatives fragment in a somewhat different manner, but several fragments characteristic to diglycine branched peptides were observed under low collision energy conditions. These signature peaks can also be used to identify peptides containing ubiquitylation sites. In addition, a marker ion corresponding to a glycine-modified lysine residue produced by high-energy fragmentation provides useful information for identity verification. The method is demonstrated by the analysis of three ubiquitin-conjugated proteins using LC/MS/MS.     

Overcoming encoder quantisation noise in an adaptive position controller

In digital position controllers, it is common to derive velocity information from a digital position encoder signal, thereby alleviating the requirement for a tachometer sensor. However, the effect of quantisation noise present in the position feedback may become problematic in certain applications. A technique is presented for overcoming the undesirable effects of encoder quantisation, when the digital encoder signal is used to derive the velocity feedback. The technique was developed to overcome quantisation noise problems identified during testing of an adaptive controller. As such, the technique involves on-line design of a model-based filter, utilising the plant parameters identified as part of the adaptive control process. The material presented has relevance also to non-adaptive, fixed parameter control systems.