Ertapenem and Faropenem against Mycobacterium tuberculosis: in vitro testing and comparison by macro and microdilution

BACKGROUND: Interest in carbapenems has been rising in the last few years due to the emergence of drug resistant tuberculosis. Ertapenem (ETP), given once a day parenteral, and faropenem (FAR), oral, have a better administration profile than meropenem (MEM), imipenem (IPM) and doripenem (DOR). The addition of amoxicillin-clavulanate (AMC) inhibits the hydrolysis by the carbapenemase present in Mycobacterium tuberculosis (MTB). The aim of this study was to determine the in vitro activity of ETP and FAR against susceptible and resistant clinical MTB strains by two widely use methodologies, the BACTEC960 MGIT and microdilution. RESULTS: 19 clinical isolates with different susceptibility profiles and H37Rv were included. Minimal inhibitory concentration (MIC) testing was performed using two methods of different concentrations of ETP and FAR with and without AMC. MIC50 was 2 and 8 for FAR with and without AMC by both methods. MIC90 was > 16 and > 8 by microdilution and MGIT respectively and did not change after AMC addition. 18/20 samples were resistant to the highest concentration of ETP, with and without AMC. Half of the samples had some susceptibility to FAR; addition of AMC further reduced the MIC level in seven isolates. 10/20 isolates showed susceptibility to FAR and the addition of AMC further reduced the MIC in 7 isolates. However, most of the MICs were near the limit of effectiveness (8 μg/mL). Resistance to FAR was associated with resistance to MEM (p = 0.04) but not to resistance profiles of other drugs, including M/XDR status. CONCLUSIONS: The lack of ETP activity may be associated with its degradation, independent of carbapenemase, during incubation. No susceptibility pattern to traditional drugs can predict susceptibility to FAR and susceptibility testing is not routinely available. PK/PD studies are needed as reaching the concentrations tested in these experiments may be challenging. This work highlighted some of the limitations of carbapenem use. More evidence is needed to clarify their true impact in TB treatment and outcome, considering the financial burden, complications and microbiota changes associated with their use

Electronic and optical properties of LiBC

LiBC, a semiconducting ternary borocarbide constituted of the lightest elements only, has been synthesized and characterized by x-ray powder diffraction, dielectric spectroscopy, and conductivity measurements. Utilizing an infrared microscope the phonon spectrum has been investigated in single crystals. The in-plane B-C stretching mode has been detected at 150 meV, noticeably higher than in AlB2, a non-superconducting isostructural analog of MgB2. It is this stretching mode, which reveals a strong electron-phonon coupling in MgB2, driving it into a superconducting state below 40 K, and is believed to mediate predicted high-temperature superconductivity in hole-doped LiBC [H. Rosner, A. Kitaigorodsky, and W. E. Pickett, Phys. Rev. Lett. 88, 127001 (2002)].Comment: 4 pages, 4 figure

Gene conversion limits divergence of mammalian TLR1 and TLR6

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLR) recognize pathogen-associated molecular patterns and are important mediators of the innate immune system. TLR1 and TLR6 are paralogs and located in tandem on the same chromosome in mammals. They form heterodimers with TLR2 and bind lipopeptide components of gram-positive and gram-negative bacterial cell walls. To identify conserved stretches in TLR1 and TLR6, that may be important for their function, we compared their protein sequences in nine mammalian species(<it>Homo sapiens</it>, <it>Pan troglodytes</it>, <it>Macaca mulatta</it>, <it>Mus musculus</it>, <it>Rattus norvegicus</it>; <it>Erinaceus europaeus</it>, <it>Bos Taurus</it>, <it>Sus scrofa </it>and <it>Canis familiaris</it>).</p> <p>Results</p> <p>The N-terminal sequences of the orthologous proteins showed greater similarity than corresponding paralog sequences. However, we identified a region of 300 amino acids towards the C-terminus of TLR1 and TLR6, where paralogs had a greater degree of sequence identity than orthologs. Preservation of DNA sequence identity of paralogs in this region was observed in all nine mammalian species investigated, and is due to independent gene conversion events. The regions having undergone gene conversion in each species are almost identical and encode the leucine-rich repeat motifs 16 to 19, the C-terminal cap motif, the transmembrane domain and most of the intracellular Toll/interleukin-1 receptor (TIR) domain.</p> <p>Conclusion</p> <p>Our results show that, for a specific conserved region, divergence of TLR1 and TLR6 is limited by gene conversion, most likely because of the need for co-evolution with multiple intracellular and extracellular binding partners. Thus, gene conversion provides a mechanism for limiting the divergence of functional regions of protein paralogs, while allowing other domains to evolve diversified functions.</p

Formation mechanisms and phase stability of solid-state grown cspbi3 perovskites

CsPbI3 inorganic perovskite is synthesized by a solvent-free, solid-state reaction, and its structural and optical properties can be deeply investigated using a multi-technique approach. X-ray Diffraction (XRD) and Raman measurements, optical absorption, steady-time and time-resolved luminescence, as well as High-Resolution Transmission Electron Microscopy (HRTEM) imaging, were exploited to understand phase evolution as a function of synthesis time length. Nanoparticles with multiple, well-defined crystalline domains of different crystalline phases were observed, usually surrounded by a thin, amorphous/out-of-axis shell. By increasing the synthesis time length, in addition to the pure α phase, which was rapidly converted into the δ phase at room temperature, a secondary phase, Cs4PbI6, was observed, together with the 715 nm-emitting γ phase

Sensor monitoring strategy

In its overall strategy, COMMON SENSE work packages (11) can be grouped into 3 key phases: (1) RD basis for cost-effective sensor development, (2) Sensor development, sensor web platform and integration, and (3) Field testing. In the Phase 1, within WP1 and WP2, partners have provided a general understanding and integrated basis for a cost effective sensors development. In Phase 2, within the WP3 and WPs 4 to 8, the new sensors have been created and planned to be integrated into instruments for the different identified platforms and how data produced will be processed, organised and saved. During the phase 3, within WP9, partners are deploying precompetitive prototypes at chosen platforms (e.g. research vessels, oil platforms, buoys and submerged moorings, ocean racing yachts, drifting buoys). Starting from August 2015 (month 22; Task 9.2), these platforms are permitting the partnership to test the adaptability and performance of the in-situ sensors and verify if the transmission of data is properly made and correct observed deviations. Sensor monitoring strategy (Deliverable 2.4 for Task 2.5) is the last task within Phase 1. As the other tasks in Phase 1 it has to provide a basis for designing field testing activities to be useful. That is how to validate the performance of sensors, integration, data acquisition, transmission, under real conditions in different platforms. Since there is a wide sensor variety, each one with its own characteristics, and several platforms, to prepare a general methodological review and give the corresponding directions as it was initially planned, would be a huge and useless effort. Given the initially fixed calendar a first version of the present deliverable was presented when most of the sensors were still not developed. The document addressed how projected sensors should be tested, their limitations and conditions for their monitoring and final certification. Now, when D2.2 (Procedures of sensors deployment methodology on physical supports/platforms) has been rewritten (May 2016), all sensors are fully developed and most of them have started their tests at sea, the present new updated version of the deliverable becomes more precise, with much better knowledge on the real sensors and their performance. In addition, a complete new chapter on data transmission –initially proposed but not developed in the previous version– is included. The information from the six sensor developers in COMMON SENSE on which the initial plan on where and how to test each sensor that was presented in D9.1 (April 2015) has been updated (May 2016). The update includes the final properties of sensors after the respective full laboratory tests and even some of the results from field tests that had been carried out starting August 2015. This task assesses field testing procedures and deployment specificities. Two tables are presented based on the information of the report for D9.1 delivered in April 2015. One table was created for sensor developers and one for those who will test the sensors at sea. In this report some information from the testers’ table is shown and updated according to the new version of D2.2 (May 2016) for platforms. Objectives and rationale The objective of Task 2.5 within the WP2 is the definition of sensor monitoring strategy based on the premises for water monitoring, sensor performances and data storage and transmission. For any new sensor, available instruments currently used in the oceanographic studies will be identified to perform comparisons. Suitable transmission technology will be selected according to the test conditions: open sea, coastal areas, remote locations, etc. Sensitivity and stress tests will be designed in order to establish confidence limits under different environmental situations, so that the results obtained in the testing exercises (WP9) will enable to certify the performance of the new instruments

Theoretical evidences for enhanced superconducting transition temperature of CaSi2_2 in a high-pressure AlB2_2 phase

By means of first-principles calculations, we studied stable lattice structures and estimated superconducting transition temperature of CaSi$_2$ at high pressure. Our simulation showed stability of the AlB$_2$ structure in a pressure range above 17 GPa. In this structure, doubly degenerated optical phonon modes, in which the neighboring silicon atoms oscillate alternately in a silicon plane, show prominently strong interaction with the conduction electrons. In addition there exists a softened optical mode (out-of-plan motion of silicon atoms), whose strength of the electron-phonon interaction is nearly the same as the above mode. The density of states at the Fermi level in the AlB$_2$ structure is higher than that in the trigonal structure. These findings and the estimation of the transition temperature strongly suggest that higher $T_{\rm c}$ is expected in the AlB$_2$ structure than the trigonal structures which are known so far.Comment: 6 pages and 11 figure

Propolis consumption reduces Nosema ceranae infection of European honey bees (Apis mellifera)

Nosema ceranae is a widespread obligate intracellular parasite of the ventriculus of many species of honey bee (Apis), including the Western honey bee Apis mellifera, in which it may lead to colony death. It can be controlled in A. mellifera by feeding the antibiotic fumagillin to a colony, though this product is toxic to humans and its use has now been banned in many countries, so in beekeeping, there exists a need for alternative and safe products effective against N. ceranae. Honeybees produce propolis from resinous substances collected from plants and use it to protect their nest from parasites and pathogens; propolis is thought to decrease the microbial load of the hive. We hypothesized that propolis might also reduce N. ceranae infection of individual bees and that they might consume propolis as a form of self-medication. To test these hypotheses, we evaluated the effects of an ethanolic extract of propolis administered orally on the longevity and spore load of experimentally N. ceranae-infected worker bees and also tested whether infected bees were more attracted to, and consumed a greater proportion of, a diet containing propolis in comparison to uninfected bees. Propolis extracts and ethanol (solvent control) increased the lifespan of N. ceranae-infected bees, but only propolis extract significantly reduced spore load. Our propolis extract primarily contained derivatives of caffeic acid, ferulic acid, ellagic acid and quercetin. Choice, scan sampling and food consumption tests did not reveal any preference of N. ceranae-infected bees for commercial candy containing propolis. Our research supports the hypothesis that propolis represents an effective and safe product to control N. ceranae but worker bees seem not to use it to self-medicate when infected with this pathogen

RVB Contribution to Superconductivity in MgB2MgB_2

We view $MgB_2$ as electronically equivalent to (non-staggered) graphite ($B^-$ layer) that has undergone a zero gap semiconductor to a superconductor phase transition by a large c-axis (chemical) pressure due to $Mg^{++}$ layers. Further, like the \ppi bonded planar organic molecules, graphite is an old resonating valence bond (RVB) system. The RVB's are the `preexisting cooper pairs' in the `parental' zero gap semiconducting $B^-$ (graphite) sheets that manifests themselves as a superconducting ground state of the transformed metal. Some consequences are pointed out.Comment: 4 pages, 2 figure, RevTex. Based on a talk given at the Institute Seminar Week, IMSc, Madras (12-16, Feb. 2001

Raman spectra and vibrational analysis of CsPbI3: a fast and reliable technique to identify lead halide perovskite polymorphs

A major issue in the development of Lead halide perovskites is the assessment of the crystal structure of the samples, due to their typically limited time-stability, and the understanding of the role of external factors that can induce a crystal phase transformation (such as humidity, intense light flux, temperature, etc.). In this perspective, it is of utmost importance to have at disposal a fast and reliable experimental tool able to give an immediate indication of the polymorph of the sample with the possibility to integrate in-situ measurements for constant monitoring. In this paper we propose Raman spectroscopy as the ideal technique to solve this problem. The vibrational analysis of CsPbI3 in the α-phase and δ-phase and of the Cs4PbI6 secondary phase is reported and all the vibrational modes are assigned by comparing experimental spectra of the phases to Raman modes calculated within the DFT framework. Finally, the mechanism of laser induced phase degradation was studied using in-situ Raman measurements providing new insights on the secondary phase generated during the process