4,779 research outputs found

    STOCHASTIC VORTEX BLOBS METHOD TO STUDY AXISYMMETRIC FLOWS OF INCOMPRESSIBLE VISCOUS FLUID

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    This paper presents the mathematical and computational formulations of the stochastic Vortex Blobs Method (VBM). It isshow that how the method can be used to cover axisymmetric flows of incompressible viscous fluid. Also, the initialboundary problem is solved by using the Lagrangian vortex method. This method seems to be an extension of the well known two dimensional vortex blob method. When applying and extending this method two steps are required. First, wehave to design an axisymmetric vorticity carrier by using the standard functions as complete elliptic integrals and Legendre polynomials. Second, it is necessary to formulate the appropriate Neumann problem and boundary integral equation to find the potential velocity fields. Both steps are used to describe and compute the total velocity field and formulate the Ito stochastic equations which describing the motion of vorticity carriers

    Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors.

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    BackgroundSchistosomiasis is one of the world's most common NTDs. Successful control operations often target snail vectors with the molluscicide niclosamide. Little is known about how niclosamide affects snails, including for Biomphalaria pfeifferi, the most important vector for Schistosoma mansoni in Africa. We used Illumina technology to explore how field-derived B. pfeifferi, either uninfected or harboring cercariae-producing S. mansoni sporocysts, respond to a sublethal treatment of niclosamide. This study afforded the opportunity to determine if snails respond differently to biotic or abiotic stressors, and if they reserve unique responses for when presented with both stressors in combination. We also examined how sporocysts respond when their snail host is treated with niclosamide.Principal findingsCercariae-producing sporocysts within snails treated with niclosamide express ~68% of the genes in the S. mansoni genome, as compared to 66% expressed by intramolluscan stages of S. mansoni in snails not treated with niclosamide. Niclosamide does not disable sporocysts nor does it seem to provoke from them distinctive responses associated with detoxifying a xenobiotic. For uninfected B. pfeifferi, niclosamide treatment alone increases expression of several features not up-regulated in infected snails including particular cytochrome p450s and heat shock proteins, glutathione-S-transferases, antimicrobial factors like LBP/BPI and protease inhibitors, and also provokes strong down regulation of proteases. Exposure of infected snails to niclosamide resulted in numerous up-regulated responses associated with apoptosis along with down-regulated ribosomal and defense functions, indicative of a distinctive, compromised state not achieved with either stimulus alone.Conclusions/significanceThis study helps define the transcriptomic responses of an important and under-studied schistosome vector to S. mansoni sporocysts, to niclosamide, and to both in combination. It suggests the response of S. mansoni sporocysts to niclosamide is minimal and not reflective of a distinct repertoire of genes to handle xenobiotics while in the snail host. It also offers new insights for how niclosamide affects snails

    Potentiometric detection of low-levels of sulfamethazine in milk and pharmaceutical formulations using novel plastic membrane sensors

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    Novel potentiometric sensors for selective screening of sulfamethazine (SMZ) in pharmaceutical preparations and milk samples are reported. The sensor membranes were made from PVC matrix doped with magnesium(II)-, manganese(II)- and dichlorotin (IV)-phthalocyanines as ionophores and aliquat-336 and nitron/SMZ ion-pair complex as ion exchangers. These sensors revealed fast, stable and near-Nernstian anionic response for the singly charged sulfamethazine anion over the concentration range 10-2 - 10-5 M. The sensors exhibited good selectivity towards SMZ over most known anions, excipients and diluents commonly added in drug preparations. Validation of the proposed methods was demonstrated via evaluating the detection limit, linear response range, accuracy, precision (within-day repeatability) and between-day-variability. The sensors are easily interfaced with a double channel flow injection system and used for continuous monitoring of SMZ in drug formulations, spiked milk samples and biological tissues. The method offers the advantages of design simplicity, results accuracy, and automation feasibility

    Functional Properties of Soy Substrates Modified by the Use of Different Enzymatic Treatments

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    The authors are grateful to Ms. Darya Sabinina from the Institute of Immunology and Physiology, Ural Branch RAS for running LC-MS experiments

    The in vivo transcriptome of Schistosoma mansoni in the prominent vector species Biomphalaria pfeifferi with supporting observations from Biomphalaria glabrata.

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    BackgroundThe full scope of the genes expressed by schistosomes during intramolluscan development has yet to be characterized. Understanding the gene products deployed by larval schistosomes in their snail hosts will provide insights into their establishment, maintenance, asexual reproduction, ability to castrate their hosts, and their prolific production of human-infective cercariae. Using the Illumina platform, the intramolluscan transcriptome of Schistosoma mansoni was investigated in field-derived specimens of the prominent vector species Biomphalaria pfeifferi at 1 and 3 days post infection (d) and from snails shedding cercariae. These S. mansoni samples were derived from the same snails used in our complementary B. pfeifferi transcriptomic study. We supplemented this view with microarray analyses of S. mansoni from B. glabrata at 2d, 4d, 8d, 16d, and 32d to highlight robust features of S. mansoni transcription, even when a different technique and vector species was used.Principal findingsTranscripts representing at least 7,740 (66%) of known S. mansoni genes were expressed during intramolluscan development, with the greatest number expressed in snails shedding cercariae. Many transcripts were constitutively expressed throughout development featuring membrane transporters, and metabolic enzymes involved in protein and nucleic acid synthesis and cell division. Several proteases and protease inhibitors were expressed at all stages, including some proteases usually associated with cercariae. Transcripts associated with G-protein coupled receptors, germ cell perpetuation, and stress responses and defense were well represented. We noted transcripts homologous to planarian anti-bacterial factors, several neural development or neuropeptide transcripts including neuropeptide Y, and receptors that may be associated with schistosome germinal cell maintenance that could also impact host reproduction. In at least one snail the presence of larvae of another digenean species (an amphistome) was associated with repressed S. mansoni transcriptional activity.Conclusions/significanceThis in vivo study, emphasizing field-derived snails and schistosomes, but supplemented with observations from a lab model, provides a distinct view from previous studies of development of cultured intramolluscan stages from lab-maintained organisms. We found many highly represented transcripts with suspected or unknown functions, with connection to intramolluscan development yet to be elucidated

    New spectrophotometric microdetermination of carbapenem antibiotics derivatives in pharmaceutical formulations

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    AbstractA new sensitive spectrophotometric method was developed to determine three carbapenem antibiotics: imipenem, meropenem and ertapenem. The proposed method was based on the formation of the coloured tris(o-phenanthroline)-iron(II) complex (ferroin) [Phen] or Fe (II)-2,2″-bipyridyl complex [Bip] in the reaction of the tested drugs with the corresponding iron (III)-complexes in an acetate pH 4 buffer. The formed coloured complexes showed maximum absorbance at 510 and 520nm for [Phen] and [Bip], respectively. The reaction conditions, including the pH, reagent concentration, reaction time, temperature and stability of the formed coloured species, were optimized to achieve the highest sensitivity. Linear calibration curves were obtained in the concentration ranges from 0.2 to 10, 0.5 to 10 and 0.5 to 10μgmL−1 for the aforementioned drugs in the same order. The developed method was successfully applied to determine the investigated carbapenems in their pharmaceutical formulations with average recoveries of 100.8, 99.8 and 99.4% for the Phen method and 98.9, 101.7 and 100.6% for the Bip method for imipenem, meropenem and ertapenem, respectively. A statistical comparison of the results with the reference method showed good concurrence and indicated no significant difference in accuracy or precision

    The CaSR in pathogenesis of breast cancer : a new target for early stage bone metastases

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    The Ca2+-sensing receptor (CaSR) is a class-C G protein-coupled receptor which plays a pivotal role in calciotropic processes, primarily in regulating parathyroid hormone secretion to maintain systemic calcium homeostasis. Among its non-calciotropic roles, where the CaSR sits at the intersection of myriad processes, it has steadily garnered attention as an oncogene or tumor suppressor in different organs. In maternal breast tissues the CaSR promotes lactation but in breast cancer it acts as an oncoprotein and has been shown to drive the pathogenesis of skeletal metastases from breast cancer. Even though research has made great strides in treating primary breast cancer, there is an unmet need when it comes to treatment of metastatic breast cancer. This review focuses on how the CaSR leads to the pathogenesis of breast cancer by contrasting its role in healthy tissues and tumorigenesis, and by drawing brief parallels with the tissues where it has been implicated as an oncogene. A class of compounds called calcilytics, which are CaSR antagonists, have also been surveyed in the instances where they have been used to target the receptor in cancerous tissues and constitute a proof of principle for repurposing them. Current clinical therapies for treating bone metastases from breast cancer are limited to targeting osteoclasts and a deeper understanding of the CaSR signaling nexus in this context can bolster them or lead to novel therapeutic interventions

    Modelling multiscale aspects of colorectal cancer

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    Colorectal cancer (CRC) is responsible for nearly half a million deaths annually world-wide [11]. We present a series of mathematical models describing the dynamics of the intestinal epithelium and the kinetics of the molecular pathway most commonly mutated in CRC, the Wnt signalling network. We also discuss how we are coupling such models to build a multiscale model of normal and aberrant guts. This will enable us to combine disparate experimental and clinical data, to investigate interactions between phenomena taking place at different levels of organisation and, eventually, to test the efficacy of new drugs on the system as a whole
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