Theoretical Examination of Solvent and R Group Dependence in Gold Thiolate Nanoparticle Synthesis

The growth of gold thiolate nanoparticles can be affected by the solvent and the R group on the ligand. In this work, the difference between methanol and benzene solvents as well as the effect of alkyl (methyl) and aromatic (phenyl) thiols on the reaction energies and barrier heights is investigated theoretically. Density functional theory (DFT) calculations using the BP86 functional and a triple ζ polarized basis set show that the overall reaction favors methylthiol over phenylthiol with reaction energies of −0.54 and −0.39 eV in methanol, respectively. At the same level of theory, the methanol solvent is favored over the benzene solvent for reactions forming ions; in benzene, the overall reaction energies for methylthiol and phenylthiol reacting with AuCl4− to form Au(HSR)2+ are 0.37 eV and 0.44 eV, respectively. Methylthiol in methanol also has the lowest barrier heights at about 0.3 eV, whereas phenylthiol has barrier heights around 0.4 eV. Barrier heights in benzene are significantly larger than those in methanol

A colorimetric competitive displacement assay for the evaluation of catalytic peptides

An assay based on competitive dye displacement was adapted to detect the formation of aldol product in crude reaction mixtures, and was used to evaluate minimal peptide aldol catalysts.</p

Metastasis-inducing S100A4 protein is associated with the disease activity of rheumatoid arthritis

Objectives. To evaluate the association between metastasis-inducing protein S100A4 and disease activity in patients with RA, and to demonstrate the effect of TNF-alpha blocking therapy on plasma levels of S100A4 in these patients. Methods. Plasma levels of the S100A4 protein were analysed in 40 anti-TNF-alpha naive patients with active RA. Of the 40 patients, 25 were treated with adalimumab and monitored over time. The conformational form of S100A4 was analysed using size-exclusion gel chromatography. TNF-alpha mRNA expression and protein synthesis were analysed by RT-PCR and ELISA, respectively. Results. Baseline levels of S100A4 were significantly correlated with disease activity in RA patients (r = 0.41; P < 0.01). After 12 weeks of treatment with adalimumab, there was an obvious shift in the conformations of S100A4 from the multimeric to the dimeric forms, whereas the total levels of the S100A4 protein remained unchanged. This suggests that the bioactive (multimer) S100A4 may decline in response to successful treatment with adalimumab. In addition, we showed significant up-regulation of TNF-alpha mRNA (P < 0.01), and protein release to the cell culture medium of monocytes stimulated with the S100A4 multimer compared with those treated with the dimer and to the unstimulated monocytes (P < 0.001). Conclusions. This is the first study to show that the levels of the S100A4 protein are correlated with RA disease activity. Furthermore, only the bioactive form, but not the total amount of S100A4, decreases after successful TNF-alpha blocking therapy in patients with RA. These data support an important role for the S100A4 multimer in the pathogenesis of R

Homeostasis of metabolites in Escherichia coli on transition from anaerobic to aerobic conditions and the transient secretion of pyruvate

We have developed a method for rapid quenching of samples taken from chemostat cultures of Escherichia coli that gives reproducible and reliable measurements of extracellular and intracellular metabolites by 1H NMR and have applied it to study the major central metabolites during the transition from anaerobic to aerobic growth. Almost all metabolites showed a gradual change after perturbation with air, consistent with immediate inhibition of pyruvate formate-lyase, dilution of overflow metabolites and induction of aerobic enzymes. Surprisingly, although pyruvate showed almost no change in intracellular concentration, the extracellular concentration transiently increased. The absence of intracellular accumulation of pyruvate suggested that one or more glycolytic enzymes might relocate to the cell membrane. To test this hypothesis, chromosomal pyruvate kinase (pykF) was modified to express either PykF-green fluorescent protein or PykF-FLAG fusion proteins. Measurements showed that PykF-FLAG relocates to the cell membrane within 5 min of aeration and then slowly returns to the cytoplasm, suggesting that on aeration, PykF associates with the membrane to facilitate secretion of pyruvate to maintain constant intracellular levels

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Aims Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Methods and results Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F2t-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. Conclusion This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT0064175

Using haloperidol as an anti-emetic in palliative care: informing practice through evidence from cancer treatment and post-operative contexts

YesNausea and vomiting are common symptoms in palliative care. Haloperidol is often used as an antiemetic in this context, although direct evidence supporting this practice is limited. To evaluate the efficacy and clinical use of haloperidol as an antiemetic in nonpalliative care contexts to inform practice, the authors conducted a rapid review of (i) published evidence to supplement existing systematic reviews, and (ii) practical aspects affecting the use of haloperidol including formulations and doses that are commonly available internationally. In nausea and vomiting related to cancer treatment, haloperidol was superior to control in two small studies. In postoperative nausea and vomiting (PONV), two randomized controlledtrials found treatment with haloperidol comparable to ondansetron. In palliative care, an observational study found a complete response rate of 24% with haloperidol (one in four patients) which would be consistent with a number needed to treat (NNT) of 3 to 5 derived from PONV. There remains insufficient direct evidence to definitively support the use of haloperidol for the management of nausea and vomiting in palliative care. However, generalizing evidence from other clinical contexts may have some validity

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Co-ordination of local policies for urban development and public transportation in four Swiss cities

The present article aims at assessing the possibility for urban areas to coordinate local policies of urban development and public transportation and at explaining the differences in this achievement between urban regions. In order to do so, the study draws support from two empirical sources: a historical analysis of the "mass-production" generated by the public service sectors in the field of transport and urban development in the cities of Basel, Bern, Geneva, and Lausanne since 1950, and a series of six case studies in these four cities. The study identifies factors located both at context level regarding morphological and geographical conditions as well as institutional settings and case-specific idiosyncrasies regarding organizational structure, past policy decisions, as well as vocational cultures that determine the possibility for urban areas to meet the need for policy coordination