Direct ortho-Arylation of Pyridinecarboxylic Acids: Overcoming the Deactivating Effect of sp2-Nitrogen

Direct arylations of pyridines are challenging transformations due to the high Lewis basicity of the sp²-nitrogen. The use of carboxylates as directing groups is reported, facilitating the Pd-catalyzed C–H arylation of this difficult class of substrates. This methodology allows regioselective C3/C4 arylation, without the need to use solvent quantities of the pyridine, and using low-cost chloro- and bromoarenes as coupling partners. Furthermore, carboxylates could be employed as traceless directing groups through a one-pot C–H arylation/Cu­(I)-mediated decarboxylation sequence, thereby accessing directing-group-free pyridine biaryls

Power and current limiting strategy based on droop controller with floating characteristic for grid-connected distributed generations

The Grid-Connected Droop-Controlled Distributed Generations (GCDCDGs) are widely used in power systems. However, their power flow is very sensitive to the Upstream Grid (UG) frequency and voltage magnitude fluctuations. This paper focuses on the power and current limiting of inverter-interfaced GCDCDGs under UG frequency and/or voltage magnitude drops. GCDCDG output power and current increase under the UG frequency drop, and if this increase exceeds the maximum of them, current limiters are saturated and according to P ∼ ω droop characteristic the GCDCDG frequency does not track the UG frequency, and this frequency difference leads to power oscillation between DG and UG and the system becomes unstable. In this paper, a new strategy based on the droop-control method is proposed to limit the output power and current of GCDCDGs without using a current limiter that realizes a stable operation under the mentioned conditions. In the proposed method instead of increasing the droop coefficients to limit P and Q at their constraints, the droop curves move down after powers and currents exceed maximum values, using two supplementary control signals. The performance of the proposed method is demonstrated with simulation results using MATLAB/Simulink environment under several case studies

Optimizing an emperical scoring function for transmembrane protein structure determination.

We examine the problem of transmembrane protein structure determination. Like many other questions that arise in biological research, this problem cannot be addressed by traditional laboratory experimentation alone. An approach that integrates experiment and computation is required. We investigate a procedure which states the transmembrane protein structure determination problem as a bound constrained optimization problem using a special empirical scoring function, called Bundler, as the objective function. In this paper, we describe the optimization problem and some of its mathematical properties. We compare and contrast results obtained using two different derivative free optimization algorithms

Developing algorithms for predicting protein-protein interactions of homology modeled proteins.

The goal of this project was to examine the protein-protein docking problem, especially as it relates to homology-based structures, identify the key bottlenecks in current software tools, and evaluate and prototype new algorithms that may be developed to improve these bottlenecks. This report describes the current challenges in the protein-protein docking problem: correctly predicting the binding site for the protein-protein interaction and correctly placing the sidechains. Two different and complementary approaches are taken that can help with the protein-protein docking problem. The first approach is to predict interaction sites prior to docking, and uses bioinformatics studies of protein-protein interactions to predict theses interaction site. The second approach is to improve validation of predicted complexes after docking, and uses an improved scoring function for evaluating proposed docked poses, incorporating a solvation term. This scoring function demonstrates significant improvement over current state-of-the art functions. Initial studies on both these approaches are promising, and argue for full development of these algorithms

Investigation of the scattering cross sections of neutrons on carbon nuclei at the reactor filtered beams

Natural carbon is well known as reactor structure material and at the same time as one of the most important neutron scattering standards, especially at energies less than 2 MeV, where the neutron total and neutron scattering cross sections are essentially identical. The best neutron total cross section experimental data for natural carbon in the range 1 - 500 keV has uncertainties of 1 - 4 %. However, the difference between these data and those based on R-matrix analysis and used in the ENDF libraries is evident; especially in the energy range 1 - 60 keV. Experimental data for total scattering neutron cross sections for this element in the energy range 1 - 200 keV are scanty. The use of the technique of neutron filtered beams developed at the Kyiv Research Reactor makes it possible to reduce the uncertainty of the experimental data and to measure the neutron scattering cross sections on natural carbon in the energy range 2 - 149 keV with accuracies of 3 - 6 %. Investigations of the neutron scattering cross section on carbon were carried out using 5 filters with energies 2, 3.5, 24, 54 and 133 keV. The neutron scattering cross sections were measured using a detector system covering nearly 2π. The detector consisting of 3 He counters (58 units), was located just above the carbon samples. The 3 He counters (CHM-37, 7 atm, diameter = 18 mm, L = 50 cm) are placed in five layers (12 or 11 in each layer). To determine the neutron scattering cross section on carbon the relative method of measurement was used. The isotope 208Pb was used as the standard. The normalization factor, which is a function of detector efficiency, thickness of the carbon samples, thickness of the 208Pb sample, geometry, etc., for each sample and for each filter energy has been obtained through Monte Carlo calculations by means of the MCNP4C code. The results of measurements of the neutron scattering cross sections at reactor neutron filtered beams with energies in the range 2 - 133 keV on carbon samples together with the known experimental data from database EXFOR/CSISRS and ENDF libraries are presented

Prospects for utilizing microbial consortia for lignin conversion

Naturally occurring microbial communities are able to decompose lignocellulosic biomass through the concerted production of a myriad of enzymes that degrade its polymeric components and assimilate the resulting breakdown compounds by members of the community. This process includes the conversion of lignin, the most recalcitrant component of lignocellulosic biomass and historically the most difficult to valorize in the context of a biorefinery. Although several fundamental questions on microbial conversion of lignin remain unanswered, it is known that some fungi and bacteria produce enzymes to break, internalize, and assimilate lignin-derived molecules. The interest in developing efficient biological lignin conversion approaches has led to a better understanding of the types of enzymes and organisms that can act on different types of lignin structures, the depolymerized compounds that can be released, and the products that can be generated through microbial biosynthetic pathways. It has become clear that the discovery and implementation of native or engineered microbial consortia could be a powerful tool to facilitate conversion and valorization of this underutilized polymer. Here we review recent approaches that employ isolated or synthetic microbial communities for lignin conversion to bioproducts, including the development of methods for tracking and predicting the behavior of these consortia, the most significant challenges that have been identified, and the possibilities that remain to be explored in this field

Chemical crosslinking and mass spectrometry studies of the structure and dynamics of membrane proteins and receptors.

Membrane proteins make up a diverse and important subset of proteins for which structural information is limited. In this study, chemical cross-linking and mass spectrometry were used to explore the structure of the G-protein-coupled photoreceptor bovine rhodopsin in the dark-state conformation. All experiments were performed in rod outer segment membranes using amino acid 'handles' in the native protein sequence and thus minimizing perturbations to the native protein structure. Cysteine and lysine residues were covalently cross-linked using commercially available reagents with a range of linker arm lengths. Following chemical digestion of cross-linked protein, cross-linked peptides were identified by accurate mass measurement using liquid chromatography-fourier transform mass spectrometry and an automated data analysis pipeline. Assignments were confirmed and, if necessary, resolved, by tandem MS. The relative reactivity of lysine residues participating in cross-links was evaluated by labeling with NHS-esters. A distinct pattern of cross-link formation within the C-terminal domain, and between loop I and the C-terminal domain, emerged. Theoretical distances based on cross-linking were compared to inter-atomic distances determined from the energy-minimized X-ray crystal structure and Monte Carlo conformational search procedures. In general, the observed cross-links can be explained by re-positioning participating side-chains without significantly altering backbone structure. One exception, between C3 16 and K325, requires backbone motion to bring the reactive atoms into sufficient proximity for cross-linking. Evidence from other studies suggests that residues around K325 for a region of high backbone mobility. These findings show that cross-linking studies can provide insight into the structural dynamics of membrane proteins in their native environment

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The interfacial bioscience grand challenge.

This report is broken down into the following 3 sections: (1) Chemical Cross-linking and Mass Spectrometry Applied to Determination of Protein Structure and Dynamics; (2) Computational Modeling of Membrane Protein Structure and Dynamics; and (3) Studies of Toxin-Membrane Interactions using Single Molecule Biophysical Methods