Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands.

Over- or under-expression of erythropoietin-production human hepatocellular receptors (Eph) and their ligands are associated with various diseases. Therefore, these molecular biomarkers can potentially be used as binding targets for the delivery of therapeutic and/or imaging agents to cells characterized by such irregular expressions. We have engineered nanoparticles derived from erythrocytes and doped with the near-infrared (NIR) FDA-approved dye, indocyanine green. We refer to these nanoparticles as NIR erythrocyte-derived transducers (NETs). We functionalized the NETs with the ligand-binding domain of a particular Eph receptor, EphB1, to target the genetically modified human dermal microvascular endothelial cells (hDMVECs) with coexpression of EphB1 receptor and its ligand ephrin-B2. This cell model mimics the pathological phenotypes of lesional endothelial cells (ECs) in port wine stains (PWSs). Our quantitative fluorescence imaging results demonstrate that such functionalized NETs bind to the ephrin-B2 ligands on these hDMVECs in a dose-dependent manner that varies sigmoidally with the number density of the particles. These nanoparticles may potentially serve as agents to target PWS lesional ECs and other diseases characterized with over-expression of Eph receptors or their associated ligands to mediate phototherapy

Gene expression signatures of pathways alterations in tumor cells caused by plant extracts

Extracts of Viscum album from different host trees (Iscador®Qu, M, P and A) and isolated mistletoe lectin showed distinct gene-expression profiles using cDNA microarrays. We were able to confirm that genes of apoptosis, the cell cycle and the immune system were affected by mistletoe preparations and we also found that signal transduction, cell communication and cancer related pathways were overregulated in the tested breast cancer (HCC-1937, MCF-7, KPL-1, Mfm-223) and lymphoma cell lines (WSZ-NHL). The effect of a specific mistletoe extract on a particular cell line was individual, so that the distinction between the reaction of the cell type and/or the influence of the mistletoe preparation could be used in targeted mistletoe therapy

Pengaruh Citra Merek dan Kualitas Produk terhadap Keputusan Pembelian Mobil Daihatsu Xenia pada PT. Astra Internasional Daihatsu Manado

Daihtasu merupakan Perusahaan otomotif yang memproduksi mobil Daihatsu Xenia. Sebagai usaha untuk menentukan keputusan pembelian mobil Daihatsu Xenia pada PT. Astra Internasional Daihatsu Manado, maka Perusahaan harus dapat membuat strategi pembelian yang baik untuk mengetahui citra merek dan kualitas produk.Tujuan penelitian adalah untuk mengetahui pengaruh citra merek dan kualitas produk terhadap keputusan pembelian mobil Daihatsu Xenia pada PT. Astra Internasional Daihatsu Manado. Penelitian ini menggunakan metode penelitian asosiatif. Sampel yang digunakan sebanyak 100 responden di PT. Astra Internasional Daihatsu Manado, dengan menggunakan metode accidental sampling. Teknik analisis data menggunakan analisis regresi linier berganda, dengan uji asumsi klasik, dan uji goodness of fit. Hasil penelitian menunjukkan secara simultan citra merek dan kualitas produk berpengaruh positif dan signifikan terhadap keputusan pembelian. Secara parsial citra merek dan kualitas produk berpengaruh terhadap keputusan pembelian. Manajemen Perusahaan sebaiknya meningkatkan fitur-fitur otomotif yang baru untuk meningkatkan citra merek dan kualitas produk sehingga dapat memberikan mutu yang tinggi bagi konsumen Perusahaan. Kata kunci : citra merek, kualitas produk, keputusan pembelia

Identifying research priorities for occupational therapy in the UK: A James Lind Alliance Priority Setting Partnership

ntroduction As the scope and nature of practice evolves in an ever-changing health and social care landscape, it is imperative the profession continues to expand the evidence base underpinning interventions. The Royal College of Occupational Therapists partnered with the James Lind Alliance to bring together people with lived experience, occupational therapists and other people working in the health and care sector to identify contemporary research priorities for the profession in the United Kingdom. Method The JLA’s well-established methodology was adopted. An opening consultation survey gathered unanswered questions. Analysis of responses and evidence checking preceded an initial prioritisation survey. The final prioritisation workshop drew on nominal group technique. Findings 927 respondents submitted 2193 questions. Those within the project’s scope were captured in 66 overarching summary questions using thematic analysis. These were initially ranked by 1140 respondents. 18 questions comprising the 10 most highly ranked by people with lived experience and by those with professional experience were considered by 19 participants in the final workshop. Together, they reached consensus on the Top 10 priorities. Conclusion These research priorities provide a contemporary framework influencing and guiding future research, ensuring it addresses the issues of greatest importance to people accessing and delivering services

Screening and techno-economic assessment of biomass-based power generation with CCS technologies to meet 2050 CO2 targets

Biomass-based power generation combined with CO2 capture and storage (Biopower CCS) currently represents one of the few practical and economic means of removing large quantities of CO2 from the atmosphere, and the only approach that involves the generation of electricity at the same time. We present the results of the Techno-Economic Study of Biomass to Power with CO2 capture (TESBiC) project, that entailed desk-based review and analysis, process engineering, optimisation as well as primary data collection from some of the leading pilot demonstration plants. From the perspective of being able to deploy Biopower CCS by 2050, twenty-eight Biopower CCS technology combinations involving combustion or gasification of biomass (either dedicated or co-fired with coal) together with pre-, oxy- or post-combustion CO2 capture were identified and assessed. In addition to the capital and operating costs, techno-economic characteristics such as electrical efficiencies (LHV% basis), Levelised Cost of Electricity (LCOE), costs of CO2 captured and CO2 avoided were modelled over time assuming technology improvements from today to 2050. Many of the Biopower CCS technologies gave relatively similar techno-economic results when analysed at the same scale, with the plant scale (MWe) observed to be the principal driver of CAPEX (£/MWe) and the cofiring % (i.e. the weighted feedstock cost) a key driver of LCOE. The data collected during the TESBiC project also highlighted the lack of financial incentives for generation of electricity with negative CO2 emissions

Mistletoe lectin is not the only cytotoxic component in fermented preparations of Viscum album from white fir (Abies pectinata)

<p>Abstract</p> <p>Background</p> <p>Preparations of mistletoe (<it>Viscum album</it>) are the form of cancer treatment that is most frequently used in the complementary medicine. Previous work has shown that these preparations are able to exert cytotoxic effects on carcinoma cells, the extent of which might be influenced by the host tree species and by the content of mistletoe lectin.</p> <p>Methods</p> <p>Using colorimetric assays, we have now compared the cytotoxic effects of <it>Viscum album </it>preparations (VAPs) obtained from mistletoe growing on oak (<it>Quercus robur </it>and <it>Q. petraea</it>, VAP-Qu), apple tree (<it>Malus domestica</it>,, VAP-M), pine (<it>Pinus sylvestris</it>, VAP-P) or white fir (<it>Abies pectinata</it>, VAP-A), on the <it>in vitro </it>growth of breast and bladder carcinoma cell lines. While MFM-223, KPL-1, MCF-7 and HCC-1937 were the breast carcinoma cell lines chosen, the panel of tested bladder carcinoma cells comprised the T-24, TCC-SUP, UM-UC-3 and J-82 cell lines.</p> <p>Results</p> <p>Each of the VAPs inhibited cell growth, but the extent of this inhibition differed with the preparation and with the cell line. The concentrations of VAP-Qu, VAP-M and VAP-A which led to a 50 % reduction of cell growth (IC₅₀) varied between 0.6 and 0.03 mg/ml. Higher concentrations of VAP-P were required to obtain a comparable effect. Purified mistletoe lectin I (MLI) led to an inhibition of breast carcinoma cell growth at concentrations lower than those of VAPs, but the sensitivity towards purified MLI did not parallel that towards VAPs. Bladder carcinoma cells were in most cases more sensitive to VAPs treatment than breast carcinoma cells. The total mistletoe lectin content was very high in VAP-Qu (54 ng/mg extract), intermediate in VAP-M (25 ng/mg extract), and very low in VAP-P (1.3 ng/mg extract) and in VAP-A (1 ng/mg extract). As to be expected from the low content of mistletoe lectin, VAP-P led to relatively weak cytotoxic effects. Most remarkably, however, the lectin-poor VAP-A revealed a cytotoxic effect comparable to, or even stronger than, that of the lectin-rich VAP-Qu, on all tested bladder and breast carcinoma cell lines.</p> <p>Conclusion</p> <p>The results suggest the existence of cytotoxic components other than mistletoe lectin in VAP-A and reveal an unexpected potential of this preparation for the treatment of breast and bladder cancer.</p

Bacterial Surface Appendages Strongly Impact Nanomechanical and Electrokinetic Properties of Escherichia coli Cells Subjected to Osmotic Stress

The physicochemical properties and dynamics of bacterial envelope, play a major role in bacterial activity. In this study, the morphological, nanomechanical and electrohydrodynamic properties of Escherichia coli K-12 mutant cells were thoroughly investigated as a function of bulk medium ionic strength using atomic force microscopy (AFM) and electrokinetics (electrophoresis). Bacteria were differing according to genetic alterations controlling the production of different surface appendages (short and rigid Ag43 adhesins, longer and more flexible type 1 fimbriae and F pilus). From the analysis of the spatially resolved force curves, it is shown that cells elasticity and turgor pressure are not only depending on bulk salt concentration but also on the presence/absence and nature of surface appendage. In 1 mM KNO3, cells without appendages or cells surrounded by Ag43 exhibit large Young moduli and turgor pressures (∼700–900 kPa and ∼100–300 kPa respectively). Under similar ionic strength condition, a dramatic ∼50% to ∼70% decrease of these nanomechanical parameters was evidenced for cells with appendages. Qualitatively, such dependence of nanomechanical behavior on surface organization remains when increasing medium salt content to 100 mM, even though, quantitatively, differences are marked to a much smaller extent. Additionally, for a given surface appendage, the magnitude of the nanomechanical parameters decreases significantly when increasing bulk salt concentration. This effect is ascribed to a bacterial exoosmotic water loss resulting in a combined contraction of bacterial cytoplasm together with an electrostatically-driven shrinkage of the surface appendages. The former process is demonstrated upon AFM analysis, while the latter, inaccessible upon AFM imaging, is inferred from electrophoretic data interpreted according to advanced soft particle electrokinetic theory. Altogether, AFM and electrokinetic results clearly demonstrate the intimate relationship between structure/flexibility and charge of bacterial envelope and propensity of bacterium and surface appendages to contract under hypertonic conditions