The Mechanism of Phase Transfer Synthesis of Silver Nanoparticles Using a Fatty Amine as Extractant/Phase Transfer Agent

The paper presents the research results on synthesizing silver nanoparticles in aqueous solutions and their extraction into the organic phase. Studies have shown that it is best to perform the extraction process using n-hexane > cyclohexane > toluene > chloroform > ethyl acetate. The results show a correlation between the dielectric constant of the organic phase and its ability to extract nanoparticles. The lower the dielectric constant is, the higher the extractability. The hydrodynamic radius of the silver nanoparticles changes after transfer to the organic phase, depending greatly on the organic phase used. The extraction mechanism is complex and multi-step. As the first step, the Ag nanoparticles are transferred to the phase boundary. As the second step, the octadecylamine (ODA) molecules adsorb on the silver nanoparticles (AgNPs) surface. The change in particle shape was also noted. This suggests that the interfacial processes are more complex than previously reported. Below the initial concentration of ODA 2 × 10−4 M, the formation of a third phase has been observed. In a one-stage experiment, the concentration of silver nanoparticles after transferring to the organic phase was increased 500 times in about 10 s. The role of the concentration of ODA, therefore, is not only a measure of the extraction efficiency and productivity but functions as an enabler to maintain favorable biphasic processing, which underlines the role of the solvent again

The BSUIN project

Baltic Sea Underground Innovation Network (BSUIN) is an European Union funded project that extends capabilities of underground laboratories. The aim of the project is to join efforts in making the underground laboratories in the Baltic Sea Region’s more accessible for innovation, business development and science by improving the availability of information about the underground facilities, service offerings, user experience, safety and marketing.The development of standards for the characterization of underground laboratories will allow to compared them with each other. This will help you choose the best places for physical measurements such as neutrino physics or searching for dark matter. The project concerns laboratories where so far no measurements have been made, and even undergrounds where there are no organized laboratories yet.The description of the BSUIN project and the first results of characterization of natural radioactive background in underground laboratories will be presented ˙ The BSUIN Project is funded by Interreg Baltic Sea funding cooperation [2]

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

The mechanism of phase transfer synthesis of silver nanoparticles using a fatty amine as extractant/phase transfer agent

The paper presents the research results on synthesizing silver nanoparticles in aqueous solutions and their extraction into the organic phase. Studies have shown that it is best to perform the extraction process using n-hexane > cyclohexane > toluene > chloroform > ethyl acetate. The results show a correlation between the dielectric constant of the organic phase and its ability to extract nanoparticles. The lower the dielectric constant is, the higher the extractability. The hydrodynamic radius of the silver nanoparticles changes after transfer to the organic phase, depending greatly on the organic phase used. The extraction mechanism is complex and multi-step. As the first step, the Ag nanoparticles are transferred to the phase boundary. As the second step, the octadecylamine (ODA) molecules adsorb on the silver nanoparticles (AgNPs) surface. The change in particle shape was also noted. This suggests that the interfacial processes are more complex than previously reported. Below the initial concentration of ODA 2 × 10−4 M, the formation of a third phase has been observed. In a one-stage experiment, the concentration of silver nanoparticles after transferring to the organic phase was increased 500 times in about 10 s. The role of the concentration of ODA, therefore, is not only a measure of the extraction efficiency and productivity but functions as an enabler to maintain favorable biphasic processing, which underlines the role of the solvent again

Crystal Structures of ABL-Related Gene (ABL2) in Complex with Imatinib, Tozasertib (VX-680), and a Type I Inhibitor of the Triazole Carbothioamide Class†

ABL2 (also known as ARG (ABL related gene)) is closely related to the well-studied Abelson kinase cABL. ABL2 is involved in human neoplastic diseases and is deregulated in solid tumors. Oncogenic gene translocations occur in acute leukemia. So far no structural information for ABL2 has been reported. To elucidate structural determinants for inhibitor interaction, we determined the cocrystal structure of ABL2 with the oncology drug imatinib. Interestingly, imatinib not only interacted with the ATP binding site of the inactive kinase but was also bound to the regulatory myristate binding site. This structure may therefore serve as a tool for the development of allosteric ABL inhibitors. In addition, we determined the structures of ABL2 in complex with VX-680 and with an ATP-mimetic type I inhibitor, which revealed an interesting position of the DFG motif intermediate between active and inactive conformations, that may also serve as a template for future inhibitor design

Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases

Treatment options for Ankylosing Spondylitis (AS) are still limited. The T helper cell 17 (Th17) pathway has emerged as a major driver of disease pathogenesis and a good treatment target. Janus kinases (JAK) are key transducers of cytokine signals in Th17 cells and therefore promising targets for the treatment of AS. Here we investigate the therapeutic potential of four different JAK inhibitors on cells derived from AS patients and healthy controls, cultured in-vitro under Th17-promoting conditions. Levels of IL-17A, IL-17F, IL-22, GM-CSF and IFN gamma were assessed by ELISA and inhibitory effects were investigated with Phosphoflow. JAK1/2/3 and TYK2 were silenced in CD4+ T cells with siRNA and effects analyzed by ELISA (IL-17A, IL-17F and IL-22), Western Blot, qPCR and Phosphoflow. In-vitro inhibition of CD4+ T lymphocyte production of multiple Th17 cytokines (IL-17A, IL-17F and IL-22) was achieved with JAK inhibitors of differing specificity, as well as by silencing of JAK1-3 and Tyk2, without impacting on cell viability or proliferation. Our preclinical data suggest JAK inhibitors as promising candidates for therapeutic trials in AS, since they can inhibit multiple Th17 cytokines simultaneously. Improved targeting of TYK2 or other JAK isoforms may confer tailored effects on Th17 responses in AS

Structural and Spectroscopic Analysis of the Kinase Inhibitor Bosutinib and an Isomer of Bosutinib Binding to the Abl Tyrosine Kinase Domain

Chronic myeloid leukemia (CML) is caused by the kinase activity of the BCR-Abl fusion protein. The Abl inhibitors imatinib, nilotinib and dasatinib are currently used to treat CML, but resistance to these inhibitors is a significant clinical problem. The kinase inhibitor bosutinib has shown efficacy in clinical trials for imatinib-resistant CML, but its binding mode is unknown. We present the 2.4 Å structure of bosutinib bound to the kinase domain of Abl, which explains the inhibitor's activity against several imatinib-resistant mutants, and reveals that similar inhibitors that lack a nitrile moiety could be effective against the common T315I mutant. We also report that two distinct chemical compounds are currently being sold under the name “bosutinib”, and report spectroscopic and structural characterizations of both. We show that the fluorescence properties of these compounds allow inhibitor binding to be measured quantitatively, and that the infrared absorption of the nitrile group reveals a different electrostatic environment in the conserved ATP-binding sites of Abl and Src kinases. Exploiting such differences could lead to inhibitors with improved selectivity

P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia

Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them