EPIC 220204960: A Quadruple Star System Containing Two Strongly Interacting Eclipsing Binaries

We present a strongly interacting quadruple system associated with the K2 target EPIC 220204960. The K2 target itself is a Kp = 12.7 magnitude star at Teff ~ 6100 K which we designate as "B-N" (blue northerly image). The host of the quadruple system, however, is a Kp = 17 magnitude star with a composite M-star spectrum, which we designate as "R-S" (red southerly image). With a 3.2" separation and similar radial velocities and photometric distances, 'B-N' is likely physically associated with 'R-S', making this a quintuple system, but that is incidental to our main claim of a strongly interacting quadruple system in 'R-S'. The two binaries in 'R-S' have orbital periods of 13.27 d and 14.41 d, respectively, and each has an inclination angle of >89 degrees. From our analysis of radial velocity measurements, and of the photometric lightcurve, we conclude that all four stars are very similar with masses close to 0.4 Msun. Both of the binaries exhibit significant ETVs where those of the primary and secondary eclipses 'diverge' by 0.05 days over the course of the 80-day observations. Via a systematic set of numerical simulations of quadruple systems consisting of two interacting binaries, we conclude that the outer orbital period is very likely to be between 300 and 500 days. If sufficient time is devoted to RV studies of this faint target, the outer orbit should be measurable within a year.Comment: 20 pages, 18 figures, 7 tables; accepted for publication in MNRA

Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present

Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (–) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (–) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease. [Int Microbiol 2015; 18(1):1-12]Keywords: Mycobacterium tuberculosis · phenotiazines · thioridazine · tuberculosi

Phenothiazines as a solution for multidrug resistant tuberculosis:From the origin to present

Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (–) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (–) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease. [Int Microbiol 2015; 18(1):1-12]Keywords: Mycobacterium tuberculosis · phenotiazines · thioridazine · tuberculosi

Defining the Structure and Receptor Binding Domain of the Leaderless Bacteriocin LsbB

Background: The bacteriocin LsbB targets a membrane-bound zinc-dependent peptidase. Results: The structure of LsbB was resolved by NMR. The C-terminal unstructured domains of LsbB and several other related bacteriocins were responsible for receptor binding. Conclusion: A subgroup of leaderless bacteriocins has been found to share a similar mechanism in receptor recognition. Significance: The study highlights the structure-function relationship of LsbB. LsbB is a class II leaderless lactococcal bacteriocin of 30 amino acids. In the present work, the structure and function relationship of LsbB was assessed. Structure determination by NMR spectroscopy showed that LsbB has an N-terminal -helix, whereas the C-terminal of the molecule remains unstructured. To define the receptor binding domain of LsbB, a competition assay was performed in which a systematic collection of truncated peptides of various lengths covering different parts of LsbB was used to inhibit the antimicrobial activity of LsbB. The results indicate that the outmost eight-amino acid sequence at the C-terminal end is likely to contain the receptor binding domain because only truncated fragments from this region could antagonize the antimicrobial activity of LsbB. Furthermore, alanine substitution revealed that the tryptophan in position 25 (Trp(25)) is crucial for the blocking activity of the truncated peptides, as well as for the antimicrobial activity of the full-length bacteriocin. LsbB shares significant sequence homology with five other leaderless bacteriocins, especially at their C-terminal halves where all contain a conserved KXXXGXXPWE motif, suggesting that they might recognize the same receptor as LsbB. This notion was supported by the fact that truncated peptides with sequences derived from the C-terminal regions of two LsbB-related bacteriocins inhibited the activity of LsbB, in the same manner as found with the truncated version of LsbB. Taken together, these structure-function studies provide strong evidence that the receptor-binding parts of LsbB and sequence-related bacteriocins are located in their C-terminal halves

Researching prisoner experiences with prison officers: an action research inspired approach

This article reports on research that incorporated action research-inspired dimensions on a project conducted in three maximum-security prisons in England. The project was aimed at collecting ethnographically informed data on prisoner experiences, at developing a method by which such data could be systematically and routinely collected by prison staff and at facilitating opportunities for prison officers to understand the ‘pains of imprisonment’ from the perspectives of prisoners. The challenges and limitations of the project are discussed, with particular reference to the paradox of participation and the role of power relations within prisons and within the research process. It is suggested that despite the inherent difficulties of attempting a participative approach with more powerful actors, facilitating change on a larger scale may be best served by developing a ‘pedagogy of the oppressors’ alongside a ‘pedagogy of the oppressed’

Chenodeoxycholic acid stimulates glucagon-like peptide-1 secretion in patients after Roux-en-Y gastric bypass

Postprandial secretion of glucagon‐like peptide‐1 (GLP‐1) is enhanced after Roux‐en‐Y gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLP‐1 secretion through activation of TGR5‐receptors. We aimed to evaluate GLP‐1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGB‐operated participants. Eleven participants (BMI 29.1 ± 1.2, age 37.0 ± 3.2 years, time from RYGB 32.3 ± 1.1 months, weight loss after RYGB 37.0 ± 3.1 kg) were studied in a placebo‐controlled, crossover‐study. On three different days, participants ingested (1) placebo (water), (2) UDCA 750 mg, (3) CDCA 1250 mg (highest recommended doses). Oral intake of CDCA increased plasma concentrations of GLP‐1, C‐peptide, glucagon, peptide YY, neurotensin, total bile acids, and fibroblast growth factor 19 significantly compared with placebo (all P < 0.05 for peak and positive incremental area‐under‐the‐curve (piAUC)). All plasma hormone concentrations were unaffected by UDCA. Neither UDCA nor CDCA changed glucose, cholecystokinin or glucose‐dependent insulinotropic polypeptide (GIP) concentrations. In conclusion, our findings demonstrate that the primary bile acid chenodeoxycholic acid is able to enhance secretion of gut hormones when administered orally in RYGB‐operated patients—even in the absence of nutrients

Effect of the molecular structure of the polymer and nucleation on the optical properties of polypropylene homo- and copolymers.

Two soluble nucleating agents were used to modify the optical properties of nine PP homo- and random copolymers. The ethylene content of the polymers changed between 0 and 5.3 wt%. Chain regularity was characterized by the stepwise isothermal segregation technique (SIST), while optical properties by the measurement of the haze of injection molded samples. Crystallization and melting characteristics were determined by differential scanning calorimetry (DSC). The analysis of the results proved that lamella thickness and change in crystallinity influence haze only slightly. A model was introduced which describes quantitatively the dependence of nucleation efficiency and haze on the concentration of the nucleating agent. The model assumes that the same factors influence the peak temperature of crystallization and optical properties. The analysis of the results proved that the assumption is valid under the same crystallization conditions. The parameters of the model depend on the molecular architecture of the polymer. Chain regularity determines supermolecular structure and thus the dependence of optical properties on nucleation

Activity of the efflux pump inhibitor SILA 421 against drug-resistant tuberculosis

Organosilicon compounds are efflux pump inhibitors with potency as an antituberculosis drug. Of the organisilicon compounds tested, SILA 421 has been shown to have a highest potency as an antituberculosis drug (1). It shares the common pathways for antimycobacterial killing with other efflux pump inhibitors: it revealed direct in vitro activity against M. tuberculosis (1), it has been shown to modify resistance by inhibiting mdr-1 efflux pumps and has shown to enhance killing of M. tuberculosis by macrophages (1)

Standard survey methods for estimating colony losses and explanatory risk factors in Apis mellifera

This chapter addresses survey methodology and questionnaire design for the collection of data pertaining to estimation of honey bee colony loss rates and identification of risk factors for colony loss. Sources of error in surveys are described. Advantages and disadvantages of different random and non-random sampling strategies and different modes of data collection are presented to enable the researcher to make an informed choice. We discuss survey and questionnaire methodology in some detail, for the purpose of raising awareness of issues to be considered during the survey design stage in order to minimise error and bias in the results. Aspects of survey design are illustrated using surveys in Scotland. Part of a standardized questionnaire is given as a further example, developed by the COLOSS working group for Monitoring and Diagnosis. Approaches to data analysis are described, focussing on estimation of loss rates. Dutch monitoring data from 2012 were used for an example of a statistical analysis with the public domain R software. We demonstrate the estimation of the overall proportion of losses and corresponding confidence interval using a quasi-binomial model to account for extra-binomial variation. We also illustrate generalized linear model fitting when incorporating a single risk factor, and derivation of relevant confidence intervals