Breakthrough paper indicator 2.0: can geographical diversity and interdisciplinarity improve the accuracy of outstanding papers prediction?

We report progress on new developments in the breakthrough paper indicator, which allows early selection of a small group of publications which may become potential breakthrough candidates based on dynamics of publication citations and certain qualitative characteristics of citations. We used a quantitative approach to identify typical citation patterns of highly cited papers. Based on these analyses, we propose two forecasting models to select groups of breakthrough paper candidates that exceed high citation thresholds five years post-publication. Here we study whether interdisciplinarity in the subject categories or geographical diversity serve as possible measures to improve ranking of breakthrough paper candidates. We found that ranked geographical diversities of known breakthrough papers have equal or better ranks than corresponding citations ranks. This allows us to apply additional filtering for better identifications of breakthrough candidates. We studied several interdisciplinarity indices, including richness, Shannon index, Simpson index, and Rao-Stirling-Porter index. We did not find any correlations between citation ranks and ranked interdisciplinarity indices.     

Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells

The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.     

Synchrotron infrared microspectroscopy detecting the evolution of Huntington's disease neuropathology and suggesting unique correlates of dysfunction in white versus gray brain matter

Huntington's disease (HD), caused by a mutation of the corresponding gene encoding the protein huntingtin (htt), is characterized by progressive deterioration of cognitive and motor functions, paralleled by extensive loss of striatal neurons. At the cellular level, pathogenesis involves an early and prolonged period of neuronal dysfunction followed by neuronal death. Understanding the molecular events driving these deleterious processes is critical to the successful development of therapies to slow down or halt the progression of the disease. Here, we examined biochemical processes in a HD ex vivo rat model, as well as in a HD model for cultured neurons using synchrotron-assisted Fourier transform infrared microspectroscopy (S-FTIRM). The model, based on lentiviral-mediated delivery of a fragment of the HD gene, expresses a mutant htt fragment in one brain hemisphere and a wild-type htt fragment in the control hemisphere. S-FTIRM allowed for high spatial resolution and distinction between spectral features occurring in gray and white matter. We measured a higher content of β-sheet protein in the striatal gray matter exposed to mutant htt as early as 4 weeks following the initiation of mutant htt exposure. In contrast, white matter tracts did not exhibit any changes in protein structure but surprisingly showed reduced content of unsaturated lipids and a significant increase in spectral features associated with phosphorylation. The former is reminiscent of changes consistent with a myelination deficiency, while the latter is characteristic of early pro-apoptotic events. These findings point to the utility of the label-free FTIRM method to follow mutant htt's β-sheet-rich transformation in striatal neurons ex vivo, provide further evidence for mutant htt amyloidogenesis in vivo, and demonstrate novel chemical features indicative of white matter changes in HD. Parallel studies in cultured neurons expressing the same htt fragments showed similar changes.     

Intracellularly Degradable Hydrogen‐Bonded Polymer Capsules

The assembly of low‐fouling polymer capsules with redox‐responsive behavior and intracellular degradability is reported. Thiol‐containing poly(2‐ethyl‐2‐oxazoline) (PEtOxMA_SH) brushes are synthesized by atom transfer radical polymerization (ATRP) of oligo(2‐ethyl‐2‐oxazoline)methacrylate and glycidyl methacrylate (GMA) and subsequent ring‐opening reaction of the GMA. Sequential deposition of PEtOxMA_SH/poly(methacrylic acid) (PMA) multilayers onto silica (SiO₂) particle templates and crosslinking through disulfide formation yield stable capsules after the removal of the SiO₂ templates by buffered hydrofluoric acid (HF). The redox‐responsive nature of the disulfide crosslinking groups enables the degradation of these capsules under simulated intracellular conditions at pH 5.9 and 5 mm glutathione (GSH). Furthermore, capsule degradation is observed after incubation with dendritic (JAWS II) cells. Even at high capsule‐to‐cell ratios, PEtOxMA_SH capsules show only negligible cytotoxicity. Quartz crystal microgravimetry (QCM) studies, using 100% human serum, reveal that films prepared from PEtOxMA_SH exhibit low‐fouling properties. The degradation and low‐fouling properties are promising for application of PEtOxMA_SH films/capsules for the delivery and triggered release of therapeutics.     

Development and application of new nucleic acid-based technologies for microbial community analyses in foods

Several challenges still persist in the analysis of microorganisms in foods, particularly in studies of complex communities. Nucleic acid-based methods are promising tools in addressing new questions concerning microbial communities. We have developed several new methods in the field of nucleic acid-based microbial community analyses. These methods cover both sample preparation and detection approaches. The sample preparation method involves simplified DNA purification using paramagnetic beads. As an extension of this method, the same paramagnetic beads are used for both cell separation and DNA purification. This enables full automation. The separate detection of viable and dead bacteria is a major issue in nucleic acid-based diagnostics. We have applied a living/dead dye that binds covalently to DNA and inhibits the PCR from dead cells. In addition, a DNA array-based detection assay has been developed. The assay combines the specificity obtained by enzymatic labeling of DNA probes with the possibility of detecting several targets simultaneously by DNA array hybridization. In combination with 16S rDNA amplification, this is a promising tool for community analyses. Also, we have developed a novel approach for multiplex quantitative PCR. The multiplex PCR has been combined with our DNA array-based detection method. Finally, we are now in the process of adapting a system for monitoring microbial growth and death in real-time through the tagging of bacteria with green fluorescent protein (GFP) combined with fluorescence detection using a high-resolution confocal laser scanner.     

Extraction of phenolic compounds from fresh leaves: A comparison of methods

The conventional sonicator/shaker bath method for phenolic extraction was compared with a less traditional one using a homogenizer. The homogenizer proved to be both more efficient and consistent in extracting phenolics from tender, as well as tough, leaves. We propose that adoption of the homogenizer technique will increase phenolic yield and efficiency.     

Automation of the elispot technique: Past, present, and future

The Elispot technique has gained much attention over the past few years. Its outstanding sensitivity and general ease of performance has made it one of the most attractive assay candidates for immunomonitoring purposes, including vaccine development and vaccine trials in various phases, diagnostics, and basic research. The demands of the market call for a simplified and automated technique in order to enhance areas of use. This paper describes past and present developments addressing the automation and standardization demands for the Elispot and indirectly connected techniques.     

Performance analysis of an integrated tangential microfilter‐fermenter

A specially designed bioreactor including an axial microfilter for cell retention was evaluated for continuous‐flow operation with selected liquid media as controls and in aerobic cultivations of Saccharomyces yeasts. In the initial tests, performance characteristics such as filtration rates and cell accumulation were assessed as a function of filter rotational speed, operating pressure, cultivation time and microfilter type (i.e. membrane or porous metal). The bioreactor did not perform satisfactorily when viscous extracellular polymer was present in the liquid. In the continuous‐flow culture enabling cell retention, Saccharomyces cerevisiae yeast cell concentrations were enhanced by as much as 16‐fold over ordinary batch growth. Concomitant filtration rates were stable over operating times of up to 130 h and hence were independent of the cell concentration. The maximum steady‐state flux was enhanced at rotational speeds up to 400‐700 rpm ranging from 22 to 42 L m^?2 h^?1. Higher rotation rates offered no further improvements. The maximum stabilized flux was independent of operating pressure. Pressure increases caused momentary flux improvements, which rapidly declined and eventually restabilized. Copyright © 2006 Society of Chemical Industry