Au nanostructured surfaces for electrochemical and localized surface plasmon resonance-based monitoring of α-synuclein-small molecule interactions.

In this proof-of-concept study, the fabrication of novel Au nanostructured indium tin oxide (Au-ITO) surfaces is described for the development of a dual-detection platform with electrochemical and localized surface plasmon resonance (LSPR)-based biosensing capabilities. Nanosphere lithography (NSL) was applied to fabricate Au-ITO surfaces. Oligomers of α-synuclein (αS) were covalently immobilized to determine the electrochemical and LSPR characteristics of the protein. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were performed using the redox probe [Fe(CN)6](3-/4-) to detect the binding of Cu(II) ions and (-)-epigallocatechin-3-gallate (EGCG) to αS on the Au-ITO surface. Electrochemical and LSPR data were complemented by Thioflavin-T (ThT) fluorescence, surface plasmon resonance imaging (SPRi), and transmission electron microscopy (TEM) studies. EGCG was shown to induce the formation of amorphous aggregates that decreased the electrochemical signals. However, the binding of EGCG with αS increased the LSPR absorption band with a bathochromic shift of 10-15 nm. The binding of Cu(II) to αS enhanced the DPV peak current intensity. NSL fabricated Au-ITO surfaces provide a promising dual-detection platform to monitor the interaction of small molecules with proteins using electrochemistry and LSPR

Evanescent-wave trapping and evaporative cooling of an atomic gas near two-dimensionality

A dense gas of cesium atoms at the crossover to two-dimensionality is prepared in a highly anisotropic surface trap that is realized with two evanescent light waves. Temperatures as low as 100nK are reached with 20.000 atoms at a phase-space density close to 0.1. The lowest quantum state in the tightly confined direction is populated by more than 60%. The system offers intriguing prospects for future experiments on degenerate quantum gases in two dimensions

Results of reference pricing and reimbursement discount rate schemes of Turkey

OBJECTIVES: General Directorate of Pharmaceuticals and Pharmacy (IEGM) is responsible for setting all prices for human medicinal products. The reference pricing system is used for setting these prices. Reference countries are reviewed annually and may be subject to certain alterations. There were 5 reference countries in 2009: Spain, Italy, Germany, France and Greece. The aim of this study is to show the distribution of reference countries which were used for reference pricing.METHODS: The price list of pharmaceuticals which was published by IEGM on 15.04.2011 was used for analysis. Distribution of reference countries and prices were evaluated.RESULTS: Prices of 6,251 generic and 3,703 original products were set according to the price list. 5,283 of generics and 3,306 of originals were in the positive list for reimbursement. Reference pricing was used for 2,352 generics and 2,281 originals. Prices of the remaining were set outside of reference pricing. 32 different countries were used for reference pricing. Italy was the most popular country for reference pricing. Even if it was not a reference country, Germany was used in some of the pharmaceuticals. The average reimbursement discount rate and price were 24.43% and 249 TL, respectively. There were no colerations between price and reimbursement discount rate, or reference country and reimbursement rate.CONCLUSION: It has been shown that Italy has the highest impact on the pricing of all pharmaceuticals in Turkey. Even if it was not a reference country, Germany showed to affect pharmaceuticals more than other countries which were also not used for reference pricing. Even if reimbursement discount rates are stated by the Social Security Institution (SGK), there are different discount rates for pharmaceuticals. The analysis stated that there were correlation between price, country and discount rates. This analysis is first for the literature. Further analysis is necessary in the light of price changes and newly launched pharmaceuticals

Optimized production of a cesium Bose-Einstein condensate

We report on the optimized production of a Bose-Einstein condensate of cesium atoms using an optical trapping approach. Based on an improved trap loading and evaporation scheme we obtain more than $10^5$ atoms in the condensed phase. To test the tunability of the interaction in the condensate we study the expansion of the condensate as a function of scattering length. We further excite strong oscillations of the trapped condensate by rapidly varying the interaction strength.Comment: 9 pages, 7 figures, submitted to Appl. Phys.

Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics

Constitutively activated STAT3 protein has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. In this study, PG-S3-001, a small molecule derived from the SH-4-54 class of STAT3 inhibitors, was found to inhibit patient-derived pancreatic cancer cell proliferation in vitro and in vivo in the low micromolar range. PG-S3-001 binds the STAT3 protein potently, Kd = 324 nmol/L by surface plasmon resonance, and showed no effect in a kinome screen (>100 cancer-relevant kinases). In vitro studies demonstrated potent cell killing as well as inhibition of STAT3 activation in pancreatic cancer cells. To better model the tumor and its microenvironment, we utilized three-dimensional (3D) cultures of patient-derived pancreatic cancer cells in the absence and presence of cancer-associated fibroblasts (CAF). In this coculture model, inhibition of tumor growth is maintained following STAT3 inhibition in the presence of CAFs. Confocal microscopy was used to verify tumor cell death following treatment of 3D cocultures with PG-S3-001. The 3D model was predictive of in vivo efficacy as significant tumor growth inhibition was observed upon administration of PG-S3-001. These studies showed that the inhibition of STAT3 was able to impact the survival of tumor cells in a relevant 3D model, as well as in a xenograft model using patient-derived cells

Polymorphisms of a Collagen-Like Adhesin Contributes to Legionella pneumophila Adhesion, Biofilm Formation Capacity and Clinical Prevalence

Legionellosis is a severe respiratory illness caused by the inhalation of aerosolized water droplets contaminated with the opportunistic pathogen Legionella pneumophila. The ability of L. pneumophila to produce biofilms has been associated with its capacity to colonize and persist in human-made water reservoirs and distribution systems, which are the source of legionellosis outbreaks. Nevertheless, the factors that mediate L. pneumophila biofilm formation are largely unknown. In previous studies we reported that the adhesin Legionella collagen-like protein (Lcl), is required for auto-aggregation, attachment to multiple surfaces and the formation of biofilms. Lcl structure contains three distinguishable regions: An N-terminal region with a predicted signal sequence, a central region containing tandem collagen-like repeats (R-domain) and a C-terminal region (C-domain) with no significant homology to other known proteins. Lcl R-domain encodes tandem repeats of the collagenous tripeptide Gly-Xaa-Yaa (GXY), a motif that is key for the molecular organization of mammalian collagen and mediates the binding of collagenous proteins to different cellular and environmental ligands. Interestingly, Lcl is polymorphic in the number of GXY tandem repeats. In this study, we combined diverse biochemical, genetic, and cellular approaches to determine the role of Lcl domains and GXY repeats polymorphisms on the structural and functional properties of Lcl, as well as on bacterial attachment, aggregation and biofilm formation. Our results indicate that the R-domain is key for assembling Lcl collagenous triple-helices and has a more preponderate role over the C-domain in Lcl adhesin binding properties. We show that Lcl molecules oligomerize to form large supramolecular complexes to which both, R and C-domains are required. Furthermore, we found that the number of GXY tandem repeats encoded in Lcl R-domain correlates positively with the binding capabilities of Lcl and with the attachment and biofilm production capacity of L. pneumophila strains. Accordingly, the number of GXY tandem repeats in Lcl influences the clinical prevalence of L. pneumophila strains. Therefore, the number of Lcl tandem repeats could be considered as a potential predictor for virulence in L. pneumophila isolates

Recent Advances in Monitoring Cell Behavior Using Cell-Based Impedance Spectroscopy

Cell-based impedance spectroscopy (CBI) is a powerful tool that uses the principles of electrochemical impedance spectroscopy (EIS) by measuring changes in electrical impedance relative to a voltage applied to a cell layer. CBI provides a promising platform for the detection of several properties of cells including the adhesion, motility, proliferation, viability and metabolism of a cell culture. This review gives a brief overview of the theory, instrumentation, and detection principles of CBI. The recent applications of the technique are given in detail for research into cancer, neurodegenerative diseases, toxicology as well as its application to 2D and 3D in vitro cell cultures. CBI has been established as a biophysical marker to provide quantitative cellular information, which can readily be adapted for single-cell analysis to complement the existing biomarkers for clinical research on disease progression

Nanocomposite of Ellagic Acid with Multi-Walled Carbon Nanotubes for the Simultaneous Voltammetric Detection of Six Biomolecules

In this proof-of-concept study, a highly sensitive electrochemical sensor using a graphite paste electrode modified with ellagic acid and multi-walled carbon nanotubes (MGPE/MWCNTs-EA) was developed for the simultaneous determination of six biomolecules: ascorbic acid (AA), dopamine (DA), uric acid (UA), tryptophan (Trp), xanthine (XA), and caffeine (CA). Differential pulse voltammetry (DPV) was performed at a potential range from 0.1–1.2 V vs. Ag/AgCl in phosphate electrolyte (pH 2.0). The modified GPE enabled the simultaneous determination of biomolecules under investigation in human urine and blood serum samples with detection limits ranging from 11–91 nM with recoveries of 94.0–106.0%. The electrochemical performance of the modified GPE for the analytes was stable and reproducible and checked with standard high performance liquid chromatography technique. The data suggested that the modified GPE provided a promising platform for routine quantitative determination of the biomolecules under investigation in quality control studies of real samples collected from food and pharmaceutical products