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Sample records for vivo investigative protocol

  1. In-vivo optical investigation of psoriasis

    Science.gov (United States)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-03-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 μm2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  2. In vivo cellular imaging using fluorescent proteins - Methods and Protocols

    Directory of Open Access Journals (Sweden)

    M. Monti

    2012-12-01

    Full Text Available The discovery and genetic engineering of fluorescent proteins has revolutionized cell biology. What was previously invisible to the cell often can be made visible with the use of fluorescent proteins. With this words, Robert M. Hoffman introduces In vivo Cellular Imaging Using Fluorescent proteins, the eighteen chapters book dedicated to the description of how fluorescence proteins have changed the way to analyze cellular processes in vivo. Modern researches aim to study new and less invasive methods able to follow the behavior of different cell types in different biological contexts: for example, how cancer cells migrate or how they respond to different therapies. Also, in vivo systems can help researchers to better understand animal embryonic development so as how fluorescence proteins may be used to monitor different processes in living organisms at the molecular and cellular level.

  3. The NICHD Investigative Interview Protocol: A Meta-Analytic Review.

    Science.gov (United States)

    Benia, Luis Roberto; Hauck-Filho, Nelson; Dillenburg, Mariana; Stein, Lilian Milnitsky

    2015-01-01

    Systematic review and meta-analysis of literature were conducted examining the effectiveness of the National Institute for Child Health and Human Development Investigative Interview Protocol in improving the quality of child forensic interviews. Online databases were searched for journal articles published between the years 2000 and 2013. Measures of interview quality were the type of interviewer utterances and the amount of information provided by children. Five studies met criteria for inclusion in the meta-analysis. Weighted mean of the effect sizes was calculated for each outcome measure. Protocol interviews had more invitations (g = 1.60) and fewer option-posing (g = -.95) and suggestive prompts (g = -.63) than standard interviews. Children interviewed by the protocol provided more central details (g = .90) in response to invitations than controls. Meta-analyses of a subset of preschool children samples revealed that protocol interviews had more invitations (g = 1.46), fewer suggestive prompts (g = -.61), and fewer option-posing prompts (g = -1.05) than controls. Findings corroborate results from previous studies that suggested the benefits of the protocol on the interviewers' performance and on children's informativeness. However, protocol did not show the same performance with regard to preschool children.

  4. In vitro and in vivo protocols of antimicrobial bioassay of medicinal herbal extracts: A review

    OpenAIRE

    Najeeb Ullah; Abida Parveen; Rahat Bano; Iqra Zulfiqar; Mukharma Maryam; Sadia Jabeen; Amna Liaqat; Sohail Ahmad

    2016-01-01

    Antimicrobial susceptibility testing against pathogenic microorganisms is the most significant task of clinical microbiology laboratory. The present study was therefore designed to review the in vitro and in vivo protocols of antimicrobial bioassays of various medicinal herbal extracts against a diversity of pathogenic microorganisms. Plants have a broad variety of antimicrobial agents which are extensively used as herbal drugs against different microbes. The review covers the ...

  5. Evaluation of home disinfection protocols for acrylic baseplates of removable orthodontic appliances: A randomized clinical investigation.

    Science.gov (United States)

    Peixoto, Iza Teixeira Alves; Enoki, Carla; Ito, Izabel Yoko; Matsumoto, Mirian Aiko Nakane; Nelson-Filho, Paulo

    2011-07-01

    In this randomized clinical trial, we investigated, using the microbial culture technique and scanning electron microscopy, the contamination of acrylic baseplates of removable orthodontic appliances by mutans streptococci (MS) and evaluated the efficacy of different home disinfection protocols with a 0.12% chlorhexidine gluconate spray (Periogard, Colgate-Palmolive, São Bernardo do Campo, Brazil). Fifteen dental students were randomly enrolled in a 3-stage changeover system with a 1-week interval between each stage. The acrylic baseplates were worn full time except at meals to simulate the routine use of removable appliances under clinical conditions. Three 1-week home disinfection protocols were tested in all stages by a different group of students: protocol I, toothbrushing + baseplate brushing + sterile tap water spraying once a day; protocol II, toothbrushing + baseplate brushing + Periogard spraying on the seventh day after appliance placement; and protocol III, toothbrushing + baseplate brushing + Periogard spraying on the fourth and seventh days after appliance placement. After the first week, the volunteers received new baseplates, toothbrushes, and dentifrices, and the regimens were repeated 2 more times. At the end of each week, the baseplates had a randomized disinfection protocol and were sent for microbiologic analysis. A scanning electron microscope was used to examine 3 acrylic baseplates representing each home protocol. The Friedman test (α = 0.05) compared the home protocols for the formation of MS colonies or biofilms on the acrylic surfaces. MS colonies or biofilms were found on all acrylic baseplates after protocol I. Protocols II and III reduced significantly (P 0.05) was observed between protocols II and III. The scanning electron microscope analysis confirmed the results of the microbiologic cultures. Disinfection of baseplates of removable orthodontic appliances by using 0.12% chlorhexidine spray once or twice a week reduced the

  6. In-vivo morphologic and spectroscopic investigation of Psoriasis

    Science.gov (United States)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-07-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  7. Ozone therapy as an adjuvant for endondontic protocols: microbiological - ex vivo study and citotoxicity analyses.

    Science.gov (United States)

    Nogales, Carlos Goes; Ferreira, Marina Beloti; Montemor, Antonio Fernando; Rodrigues, Maria Filomena de Andrade; Lage-Marques, José Luiz; Antoniazzi, João Humberto

    2016-01-01

    This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I - control; Group II - standard protocol; Group III - standard protocol + ozone gas at 40 µg/mL; and Group IV - standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) - broth medium; Group II - aqueous ozone at 2 µg/mL; Group III - aqueous ozone at 5 µg/mL; and Group IV - aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results.

  8. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    Science.gov (United States)

    NOGALES, Carlos Goes; FERREIRA, Marina Beloti; MONTEMOR, Antonio Fernando; RODRIGUES, Maria Filomena de Andrade; Lage-MARQUES, José Luiz; ANTONIAZZI, João Humberto

    2016-01-01

    ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results. PMID:28076466

  9. Samples and Sampling Protocols for Scientific Investigations | Joel ...

    African Journals Online (AJOL)

    ... from sampling, through sample preparation, calibration to final measurement and reporting. This paper, therefore offers useful information on practical guidance on sampling protocols in line with best practice and international standards. Keywords: Sampling, sampling protocols, chain of custody, analysis, documentation ...

  10. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    Directory of Open Access Journals (Sweden)

    Carlos Goes NOGALES

    Full Text Available ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (p<0.05%. Results The results revealed antimicrobial efficacy by Group IV with no CFU count. The cytotoxicity assay showed Groups III and IV to be the most aggressive, providing a decrease in cell viability at hour 0 from 100% to 77.3% and 68.6%, respectively. Such a decrease in cell viability was reverted, and after 72 hours Groups III and IV provided the greatest increase in cell viability, being statistically different from Groups I and II. Conclusion According to the applied methodology and the limitations of this study, it was possible to conclude that ozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results.

  11. Structured forensic interview protocols improve the quality and informativeness of investigative interviews with children: A review of research using the NICHD Investigative Interview Protocol

    Science.gov (United States)

    Lamb, Michael E.; Orbach, Yael; Hershkowitz, Irit; Esplin, Phillip W.; Horowitz, Dvora

    2007-01-01

    Objective To show how the results of research on children’s memory, communicative skills, social knowledge, and social tendencies can be translated into guidelines that improve the quality of forensic interviews of children. Method We review studies designed to evaluate children’s capacities as witnesses, explain the development of the structured NICHD Investigative Interview Protocol, and discuss studies designed to assess whether use of the Protocol enhances the quality of investigative interviews. Results Controlled studies have repeatedly shown that the quality of interviewing reliably and dramatically improves when interviewers employ the NICHD Protocol. No other technique has been proven to be similarly effective. Conclusions Use of the structured NICHD Protocol improves the quality of information obtained from alleged victims by investigators, thereby increasing the likelihood that interventions will be appropriate. PMID:18023872

  12. Quantitative Comparison of 21 Protocols for Labeling Hippocampal Subfields and Parahippocampal Cortical Subregions in In Vivo MRI: Towards Developing a Harmonized Segmentation Protocol

    DEFF Research Database (Denmark)

    Yushkevich, Paul A.; Amaral, Robert S.C.; Augustinack, Jean C.

    2015-01-01

    of guiding subsequent work on developing a harmonized substructure segmentation protocol. Method: MRI scans of a single healthy adult human subject were acquired both at 3 T and 7 T. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities......Objective: An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1 − 3, and the subiculum) and subregions of the parahippocampal gyrus...... of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal...

  13. Fluorescence investigations to classify malignant laryngeal lesions in vivo

    DEFF Research Database (Denmark)

    Rydell, Roland; Eker, Charlotta; Andersson-Engels, Stefan

    2008-01-01

    BACKGROUND: The extent of surgical resection for malignant laryngeal lesions influences voice quality. An instrument to estimate histopathologic grading of dysplasia in vivo may spare normal tissue without increasing the risk of local failure. METHODS: Laryngeal lesions (N = 39; 21 after...... administration of delta-aminolevulinic acid (ALA)) were investigated with laser-induced fluorescence, and the results correlated to histopathologic grading in 4 groups: non/mild dysplasia (I), moderate dysplasia (II), severe dysplasia/cancer in situ (III), and carcinoma. RESULTS: At 337-nm excitation, there were...... differences in the fluorescence ratio I(431)/I(390) between groups I/III and carcinoma. Following 405-nm excitation, I(500 nm) group I differed significantly from group III and cancer. The sensitivity for the fluorescence method was 89%, and the specificity was 100%. CONCLUSIONS: There are differences...

  14. Considerations when investigating lncRNA function in vivo.

    Science.gov (United States)

    Bassett, Andrew R; Akhtar, Asifa; Barlow, Denise P; Bird, Adrian P; Brockdorff, Neil; Duboule, Denis; Ephrussi, Anne; Ferguson-Smith, Anne C; Gingeras, Thomas R; Haerty, Wilfried; Higgs, Douglas R; Miska, Eric A; Ponting, Chris P

    2014-08-14

    Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans-effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of lncRNAs in the light of different models of lncRNA molecular mechanism, and reflect on the design of experiments to mutate lncRNA loci. These considerations should assist in the further investigation of these transcriptional products of the genome. Copyright © 2014, Bassett et al.

  15. Assessing pragmatic language in autism spectrum disorder: the Yale in vivo Pragmatic Protocol.

    Science.gov (United States)

    Schoen Simmons, Elizabeth; Paul, Rhea; Volkmar, Fred

    2014-12-01

    This study compared pragmatic language in youths (9-17 years) with autism spectrum disorder (ASD) and those with typical development (TD) on the Yale in vivo Pragmatic Protocol (YiPP), a semistructured, dynamic conversational assessment. Participants (n = 118) were divided into groups based on age and diagnosis. Each completed the YiPP, which included 4 pragmatic domains (discourse management, communicative functions, conversational repair, presupposition). The participant's response to each probe was scored correct or incorrect; incorrect scores elicited cues from the examiner, and level of cue required for a correction was also scored. The YiPP showed high reliability and internal consistency, with moderate concurrent validity, sensitivity, and specificity. The group with ASD performed worse overall on YiPP probes compared to their TD counterparts on both error (d = 0.96) and cue (d = 0.91) scores. Item analyses revealed greater gaps between older students with ASD and their TD peers than between the 2 younger groups. These data suggest that a probe measure designed to assess pragmatic abilities in children with ASD within a conversational context has some validity for contributing to diagnostic classification and can identify specific areas of pragmatic vulnerabilities as part of a clinical assessment.

  16. In vitro and in vivo protocols of antimicrobial bioassay of medicinal herbal extracts: A review

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2016-08-01

    Full Text Available Antimicrobial susceptibility testing against pathogenic microorganisms is the most significant task of clinical microbiology laboratory. The present study was therefore designed to review the in vitro and in vivo protocols of antimicrobial bioassays of various medicinal herbal extracts against a diversity of pathogenic microorganisms. Plants have a broad variety of antimicrobial agents which are extensively used as herbal drugs against different microbes. The review covers the antimicrobial techniques and antimicrobial bioassays of medicinal herbal extracts against different bacterial and fungal strains from 2000 onward. Plants have diverse concentrations of bioactive constituents such as alkaloids, saponins, tannins, terpenoids, steroids, carbohydrates, proteins and lipids. These phytochemicals are used against an extensive range of bacteria (Escherichia coli, Mycobacterium, Corynebacterium pervum, Bordetella pertusis, Klebsiella pneumoniae, Salmonella typhi, viruses (simian-virus, retrovirus and fungi (Pseudomonas aeruginosa, Aspergillus fumigatus, Aspergillus flavus, Fusarium solani. A variety of antibiotics (tetracycline, terramycin, ampicillin has also been isolated from different medicinal plants. This review was therefore intended to explore the techniques used for antimicrobial activities of herbal medicinal extracts.

  17. Quantitative Comparison of 21 Protocols for Labeling Hippocampal Subfields and Parahippocampal Subregions in In Vivo MRI: Towards a Harmonized Segmentation Protocol

    Science.gov (United States)

    Yushkevich, Paul A.; Amaral, Robert S. C.; Augustinack, Jean C.; Bender, Andrew R.; Bernstein, Jeffrey D.; Boccardi, Marina; Bocchetta, Martina; Burggren, Alison C.; Carr, Valerie A.; Chakravarty, M. Mallar; Chetelat, Gael; Daugherty, Ana M.; Davachi, Lila; Ding, Song-Lin; Ekstrom, Arne; Geerlings, Mirjam I.; Hassan, Abdul; Huang, Yushan; Iglesias, Eugenio; La Joie, Renaud; Kerchner, Geoffrey A.; LaRocque, Karen F.; Libby, Laura A.; Malykhin, Nikolai; Mueller, Susanne G.; Olsen, Rosanna K.; Palombo, Daniela J.; Parekh, Mansi B; Pluta, John B.; Preston, Alison R.; Pruessner, Jens C.; Ranganath, Charan; Raz, Naftali; Schlichting, Margaret L.; Schoemaker, Dorothee; Singh, Sachi; Stark, Craig E. L.; Suthana, Nanthia; Tompary, Alexa; Turowski, Marta M.; Van Leemput, Koen; Wagner, Anthony D.; Wang, Lei; Winterburn, Julie L.; Wisse, Laura E.M.; Yassa, Michael A.; Zeineh, Michael M.

    2015-01-01

    OBJECTIVE An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1–3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. METHOD MRI scans of a single healthy adult human subject were acquired both at 3 Tesla and 7 Tesla. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement. RESULTS The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail. CONCLUSIONS The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies. PMID

  18. Template protocol for clinical trials investigating vaccines—Focus on safety elements☆

    Science.gov (United States)

    Bonhoeffer, Jan; Imoukhuede, Egeruan B.; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B.; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

    2015-01-01

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

  19. Template protocol for clinical trials investigating vaccines Focus on safety elements

    OpenAIRE

    Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe

    2013-01-01

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts.

  20. Investigation into Practical Implementations of a Zero Knowledge Protocol.

    Energy Technology Data Exchange (ETDEWEB)

    Marleau, Peter [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Krentz-Wee, Rebecca E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    In recent years, the concept of Zero Knowledge Protocols (ZKP) as a useful approach to nuclear warhead verification has become increasingly popular. Several implementations of ZKP have been proposed, driving technology development toward proof of concept demonstrations. Whereas proposed implementations seem to fall within the general class of template-based techniques, all physical implementations of ZKPs proposed to date have a complication: once the instrumentation is prepared, it is no longer authenticatable; the instrument physically contains sensitive information. In this work we explore three different concepts that may offer more authenticatable and practical ZKP implementations and evaluate the sensitive information that may be at risk when doing so: sharing a subset of detector counts in a preloaded image (with spatial information removed), real-time image subtraction, and a new concept, CONfirmation using a Fast-neutron Imaging Detector with Anti-image NULL-positive Time Encoding (CONFIDANTE). CONFIDANTE promises to offer an almost ideal implementation of ZKP: a positive result is indicated by a constant rate at all times enabling the monitoring party the possibility of full access to the instrument before, during, and after confirmation. A prototype of CONFIDANTE was designed, built, and its performance evaluated in a series of measurements of several objects including a set of plutonium dioxide Hemispheres. Very encouraging results proving feasibility are presented. 1 Rebecca is currently a graduate student in Nuclear Engineering at UC Berkeley

  1. Investigating Long-Term Monitoring Protocols in support of Quivira NWR Habitat Objectives

    Data.gov (United States)

    Department of the Interior — The project purpose is to investigate long-term monitoring protocols in support of Quivira NWR habitat objectives as described in the Refuge’s recently approved CCP...

  2. Children's Coping with "In Vivo" Peer Rejection: An Experimental Investigation

    Science.gov (United States)

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J.

    2006-01-01

    We examined children's behavioral coping in response to an "in vivo" peer rejection manipulation. Participants (N = 186) ranging between 10 and 13 years of age, played a computer game based on the television show "Survivor" and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min.…

  3. Template protocol for clinical trials investigating vaccines--focus on safety elements.

    Science.gov (United States)

    Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

    2013-11-12

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. An In-vivo investigation of transverse flow estimation

    DEFF Research Database (Denmark)

    Udesen, Jesper; Jensen, Jørgen Arendt

    2004-01-01

    Conventional ultrasound scanners are restricted to display the blood velocity component in the ultrasound beam direction. By introducing a laterally oscillating field, signals are created from which the transverse velocity component can be estimated. This paper presents velocity and volume flow...... estimates obtained from flow phantom and in-vivo measurements at 90° relative to the ultrasound beam axis. The flow phantom experiment setup consists of a SMI140 flow phantom connected to a CompuFlow1000 programmable flow pump, which generates a flow similarly to that in the femoral artery. A B-K medical...... 8804 linear array transducer with 128 elements and a center frequency of 7 MHz is emitting 8 cycle ultrasound pulses with a pulse repetition frequency of 7 kHz in a direction perpendicular to the flow direction in the phantom. The transducer is connected to the experimental ultrasound scanner RASMUS...

  5. Children's coping with in vivo peer rejection: an experimental investigation.

    Science.gov (United States)

    Reijntjes, Albert; Stegge, Hedy; Terwogt, Mark Meerum; Kamphuis, Jan Henk; Telch, Michael J

    2006-12-01

    We examined children's behavioral coping in response to an in vivo peer rejection manipulation. Participants (N=186) ranging between 10 and 13 years of age, played a computer game based on the television show Survivor and were randomized to either peer rejection (i.e., being voted out of the game) or non-rejection control. During a five-min. post-feedback waiting period children's use of several behavioral coping strategies was assessed. Rejection elicited a marked shift toward more negative affect, but higher levels of perceived social competence attenuated the negative mood shift. Children higher in depressive symptoms were more likely to engage in passive and avoidant coping behavior. Types of coping were largely unaffected by gender and perceived social competence. Implications are discussed.

  6. In vivo HAPLOID INDUCTION AND EFFICIENCY OF TWO CHROMOSOME DUPLICATION PROTOCOLS IN TROPICAL MAIZE

    Directory of Open Access Journals (Sweden)

    Evellyn Giselly de Oliveira Couto

    2015-10-01

    Full Text Available ABSTRACTArtificial chromosome duplication is one of the most important process in the attainment of doubled haploids in maize. This study aimed to evaluate the induction ability of the inducer line KEMS in a tropical climate and test the efficiency of the R1-Navajo marker by flow cytometry to evaluate two chromosome duplication protocols and analyze the development of the doubled haploids in the field. To accomplish this goal, four genotypes (F1 and F2 generations were crossed with the haploid inducer line KEMS. The seeds obtained were selected using the R1-Navajo marker and subject to two chromosome duplication protocols. Duplication was confirmed using flow cytometry. The percentages of self-fertilized plants after duplication as well as the quantities of doubled haploid seeds obtained after the self-fertilization processes were analyzed. It was observed that the germplasm influences haploid induction but not the duplication rates of the tested protocols. Protocol 2 was more efficient for the duplication of haploids, in the percentage of self-fertilized plants after duplication, and in the attainment of doubled haploid lines. Moreover, the haploid inducer line KEMS can produce haploids in a tropical climate. Other markers, in addition to the R1-Navajo system, should be used in the selection of haploid seeds.

  7. An easy and efficient permeabilization protocol for in vivo enzyme activity assays in cyanobacteria

    DEFF Research Database (Denmark)

    Rasmussen, Randi Engelberth; Erstad, Simon Matthé; Ramos Martinez, Erick Miguel

    2016-01-01

    , lysis of cyanobacterial cells is inefficient and often laborious. In some cases radioisotope-labeled substrates can be fed directly to intact cells; however, label-free assays are often favored due to safety and practical reasons. RESULTS: Here we show an easy and highly efficient method...... and subsequent activity assays were successfully adapted to the 96-well plate system. CONCLUSIONS: An easy, efficient and scalable permeabilization protocol was established for cyanobacteria. The permeabilized cells can be directly applied for measurement of G6PDH and Rubisco activities without using...... radioisotopes and the protocol may be readily adapted to studies of other cyanobacterial species and other intracellular enzymes. The permeabilization and enzyme assays can be performed in 96-well plates in a high-throughput manner....

  8. Evaluation of Cyanea capillata Sting Management Protocols Using Ex Vivo and In Vitro Envenomation Models.

    Science.gov (United States)

    Doyle, Thomas K; Headlam, Jasmine L; Wilcox, Christie L; MacLoughlin, Eoin; Yanagihara, Angel A

    2017-07-07

    Lion's mane jellyfish (Cyanea capillata) stings cause severe pain and can lead to dangerous systemic effects, including Irukandji-like syndrome. As is the case for most cnidarian stings, recommended medical protocols in response to such stings lack rigorous scientific support. In this study, we sought to evaluate potential first aid care protocols using previously described envenomation models that allow for direct measurements of venom activity. We found that seawater rinsing, the most commonly recommended method of tentacle removal for this species, induced significant increases in venom delivery, while rinsing with vinegar or Sting No More(®) Spray did not. Post-sting temperature treatments affected sting severity, with 40 min of hot-pack treatment reducing lysis of sheep's blood (in agar plates), a direct representation of venom load, by over 90%. Ice pack treatment had no effect on sting severity. These results indicate that sting management protocols for Cyanea need to be revised immediately to discontinue rinsing with seawater and include the use of heat treatment.

  9. Evaluation of Cyanea capillata Sting Management Protocols Using Ex Vivo and In Vitro Envenomation Models

    Directory of Open Access Journals (Sweden)

    Thomas K. Doyle

    2017-07-01

    Full Text Available Lion’s mane jellyfish (Cyanea capillata stings cause severe pain and can lead to dangerous systemic effects, including Irukandji-like syndrome. As is the case for most cnidarian stings, recommended medical protocols in response to such stings lack rigorous scientific support. In this study, we sought to evaluate potential first aid care protocols using previously described envenomation models that allow for direct measurements of venom activity. We found that seawater rinsing, the most commonly recommended method of tentacle removal for this species, induced significant increases in venom delivery, while rinsing with vinegar or Sting No More® Spray did not. Post-sting temperature treatments affected sting severity, with 40 min of hot-pack treatment reducing lysis of sheep’s blood (in agar plates, a direct representation of venom load, by over 90%. Ice pack treatment had no effect on sting severity. These results indicate that sting management protocols for Cyanea need to be revised immediately to discontinue rinsing with seawater and include the use of heat treatment.

  10. Anti-atrial Fibrillatory Versus Proarrhythmic Potentials of Amiodarone: A New Protocol for Safety Evaluation In Vivo.

    Science.gov (United States)

    Matsukura, Suchitra; Nakamura, Yuji; Cao, Xin; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Sugiyama, Atsushi

    2017-04-01

    Anti-atrial fibrillatory and proarrhythmic potentials of amiodarone were simultaneously analyzed by using the halothane-anesthetized beagle dogs (n = 4) in order to begin to prepare standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of 0.3 mg/kg of amiodarone hydrochloride decreased the heart rate and mean blood pressure. Additional administration of 3 mg/kg of amiodarone hydrochloride prolonged the QT interval besides the effects observed by the low dose, whereas it showed 1.6 times larger prolongation in the effective refractory period of the atrium than that of the ventricle, which may explain its clinical efficacy against atrial arrhythmias. However, no significant change was detected by either dose in the early repolarization assessed by corrected J-T peak or the late repolarization done by T peak-T end in the electrocardiogram, although the former tended to be shortened and the reverse was true for the latter. Lack of prolongation in the early repolarization will make it feasible to better understand why amiodarone lacks proarrhythmic potential in spite of the QT-interval prolongation. Thus, these results of amiodarone obtained by current protocol may become a guidance on assessing efficacy and adverse effects of new anti-atrial fibrillatory drugs in vivo.

  11. Cheating and Anti-Cheating in Gossip-Based Protocol: An Experimental Investigation

    Science.gov (United States)

    Xiao, Xin; Shi, Yuanchun; Tang, Yun; Zhang, Nan

    During recent years, there has been a rapid growth in deployment of gossip-based protocol in many multicast applications. In a typical gossip-based protocol, each node acts as dual roles of receiver and sender, independently exchanging data with its neighbors to facilitate scalability and resilience. However, most of previous work in this literature seldom considered cheating issue of end users, which is also very important in face of the fact that the mutual cooperation inherently determines overall system performance. In this paper, we investigate the dishonest behaviors in decentralized gossip-based protocol through extensive experimental study. Our original contributions come in two-fold: In the first part of cheating study, we analytically discuss two typical cheating strategies, that is, intentionally increasing subscription requests and untruthfully calculating forwarding probability, and further evaluate their negative impacts. The results indicate that more attention should be paid to defending cheating behaviors in gossip-based protocol. In the second part of anti-cheating study, we propose a receiver-driven measurement mechanism, which evaluates individual forwarding traffic from the perspective of receivers and thus identifies cheating nodes with high incoming/outgoing ratio. Furthermore, we extend our mechanism by introducing reliable factor to further improve its accuracy. The experiments under various conditions show that it performs quite well in case of serious cheating and achieves considerable performance in other cases.

  12. Response surface optimization, Ex vivo and In vivo investigation of nasal spanlastics for bioavailability enhancement and brain targeting of risperidone.

    Science.gov (United States)

    Abdelrahman, Fatma Elzahraa; Elsayed, Ibrahim; Gad, Mary Kamal; Elshafeey, Ahmed Hassen; Mohamed, Magdi Ibrahim

    2017-09-15

    Transnasal brain drug targeting could ensure better drug delivery to the brain through the olfactory pathway. Risperidone bioavailability is 66% in extensive metabolizers and 82% in slow metabolizers. The aim of this study is to investigate the ability of the nanovesicular spanlastics to effectively deliver risperidone through the nasal route to the brain and increase its bioavailability. Spanlastics formulae, composed of span and polyvinyl alcohol, were designed based on central composite statistical design. The planned formulae were prepared using ethanol injection method. The prepared formulae were characterized by testing their particle size, polydispersity index, zeta potential and encapsulation efficiency. The optimized formula having the lowest particle size, polydispersity index, the highest zeta potential and encapsulation efficiency was subjected to further investigations including characterization of its rheological properties, elasticity, transmission electron microscopy, in vitro diffusion, ex vivo permeation, histopathology and in vivo biodistribution. The optimized formula was composed of 5mg/mL span and 30mg/mL polyvinyl alcohol. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the used control regarding the brain targeting efficiency and the drug transport percentage (2.16 and 1.43 folds increase, respectively). The study introduced a successful and promising formula to directly and effectively carry the drug from nose to brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Plasticity-Inducing TMS Protocols to Investigate Somatosensory Control of Hand Function

    Directory of Open Access Journals (Sweden)

    M. Jacobs

    2012-01-01

    Full Text Available Hand function depends on sensory feedback to direct an appropriate motor response. There is clear evidence that somatosensory cortices modulate motor behaviour and physiology within primary motor cortex. However, this information is mainly from research in animals and the bridge to human hand control is needed. Emerging evidence in humans supports the notion that somatosensory cortices modulate motor behaviour, physiology and sensory perception. Transcranial magnetic stimulation (TMS allows for the investigation of primary and higher-order somatosensory cortices and their role in control of hand movement in humans. This review provides a summary of several TMS protocols in the investigation of hand control via the somatosensory cortices. TMS plasticity inducing protocols reviewed include paired associative stimulation, repetitive TMS, theta-burst stimulation as well as other techniques that aim to modulate cortical excitability in sensorimotor cortices. Although the discussed techniques may modulate cortical excitability, careful consideration of experimental design is needed to isolate factors that may interfere with desired results of the plasticity-inducing protocol, specifically events that may lead to metaplasticity within the targeted cortex.

  14. Comparison of different vitrification protocols on viability after transfer of ovine blastocysts in vitro produced and in vivo derived.

    Science.gov (United States)

    Dattena, M; Accardo, C; Pilichi, S; Isachenko, V; Mara, L; Chessa, B; Cappai, P

    2004-08-01

    We compare different vitrification protocols on the pregnancy and lambing rate of in vitro produced (IVP) and in vivo derived (IVD) ovine embryos. Ovine blastocysts were produced by in vitro maturation, fertilization and culture of oocytes collected from slaughtered ewes or superovulated and inseminated animals. Embryos were cryopreserved after exposure at room temperature either for 5 min in 10% glycerol (G), then for 5 min in 10% G + 20% ethylene glycol (EG), then for 30 s in 25% G + 25% EG (glycerol group), or for 3 min in 10% EG + 10% dimethyl sulphoxide (DMSO), then for 30s in 20% EG + 20% DMSO + 0.3 M sucrose (DMSO group). One group of in vitro produced embryos was cryopreserved similarly to the DMSO group, but with 0.75 M sucrose added to the vitrification solution (DMSO 0.75 group). Glycerol group embryos were then loaded into French straws or open pulled Straws (OPS) while the DMSO group embryos were all loaded into OPS and directly plunged into liquid nitrogen. Embryos were warmed with either a one step or three step process. In the one step process, embryos were placed in 0.5 M sucrose. The three-step process was a serial dilution in 0.5, 0.25 and 0.125 M sucrose. The embryos of DMSO 0.75 group were warmed directly by plunging them into tissue culture medium-199 (TCM-199) + 20% foetal bovine serum (FBS) in the absence of sucrose (direct dilution). Following these manipulations, the embryos were transferred in pairs into synchronised recipient ewes and allowed to go to term. The pregnancy and the lambing rate within each group of IVP and IVD embryos indicated that there was no statistical difference among the vitrification protocols.

  15. Microdialysis as a tool for in vivo investigation of glutamate transport capacity in rat brain

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    1995-01-01

    technique, we present a method that is suitable for the in vivo investigation of the capacity of cellular uptake of glutamate. Using 14C-mannitol as reference, we measured the cellular extraction and the cell membrane permeability of the test substance 3H-D-aspartate in the corpus striatum of the rat brain...

  16. Do ultrasonic dental scalers interfere with implantable cardioverter defibrillators? An in vivo investigation

    National Research Council Canada - National Science Library

    Maiorana, Carlo; Grossi, Giovanni B; Garramone, Rocco A; Manfredini, Ruggero; Santoro, Franco

    2013-01-01

    .... Ultrasonic dental scalers have been suspected of electromagnetic interference (EMI) with the normal functioning of ICDs and the use of this type of equipment for patients with these devices has been controversial. This is the first in vivo study to investigate EMI of ICD activity during the operation with ultrasonic dental scaler.

  17. Treatment of acquired hemophilia by the Bonn-Malmo Protocol: documentation of an in vivo immunomodulating concept.

    Science.gov (United States)

    Zeitler, Heike; Ulrich-Merzenich, Gudrun; Hess, Lothar; Konsek, Eligius; Unkrig, Christoph; Walger, Peter; Vetter, Hans; Brackmann, Hans-Hermann

    2005-03-15

    Acquired hemophilia (AH) is an extremely rare condition in which autoantibodies (inhibitors) against clotting factor VIII induce acute and life-threatening hemorrhagic diathesis because of abnormal blood clotting. The mortality rate of AH is as high as 16%, and current treatment options are associated with adverse side effects. We investigated a therapeutic approach for AH called the modified Bonn-Malmo Protocol (MBMP). The aims of MBMP include suppression of bleeding, permanent elimination of inhibitors, and development of immune tolerance, thereby avoiding long-term reliance on coagulation products. The protocol included immunoadsorption for inhibitor elimination, factor VIII substitution, intravenous immunoglobulin, and immunosuppression. Thirty-five high-titer patients with critical bleeding who underwent MBMP were evaluated. Bleeding was rapidly controlled during 1 or 2 apheresis sessions, and no subsequent bleeding episodes occurred. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% confidence interval [95% CI], 2-4 days), factor substitution was stopped within a median of 12 days (95% CI, 11-17 days), and treatment was completed within a median of 14 days (95% CI, 12-17 days). Long-term follow-up (7 months-7 years) showed an overall response rate of 88% for complete remission (CR). When cancer patients were excluded, the CR rate was 97%.

  18. Optimizing the imaging protocol for vivo coronary artery wall using high-resolution MIRI: An experimental study on porcine and human

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jiang; Li, Tao; Cul, Xiaoming; Zhou, Weihua; Zhang, Xinwu [The General Hospital of Chinese People' s Armed Police Forces, Beijing (China)

    2013-08-15

    To optimize the MR imaging protocol for coronary arterial wall depiction in vitro and characterize the coronary atherosclerotic plaques. MRI examination was prospectively performed in ten porcine hearts in order to optimize the MR imaging protocol. Various surface coils were used for coronary arterial wall imaging with the same parameters. Then, the image parameters were further optimized for high-resolution coronary wall imaging. The signal-noise ratio (SNR) and contrast-noise ratio (CNR) of images were measured. Finally, 8 human cadaver hearts with coronary atherosclerotic plaques were prospectively performed with MRI examination using optimized protocol in order to characterize the coronary atherosclerotic plaques. The SNR and CNR of MR image with temporomandibular coil were the highest of various surface coils. High-resolution and high SNR and CNR for ex vivo coronary artery wall depiction can be achieved using temporomandibular coil with 512 x 512 in matrix. Compared with histopathology, the sensitivity and specificity of MRI for identifying advanced plaques were: type IV-V (lipid, necrosis, fibrosis), 94% and 95%; type VI (hemorrhage), 100% and 98%; type VII (calcification), 91% and 100%; and type VIII (fibrosis without lipid core), 100% and 98%, respectively. Temporomandibular coil appears to be dramatically superior to eight-channel head coil and knee coil for ex vivo coronary artery wall imaging, providing higher spatial resolution and improved the SNR. Ex vivo high-resolution MRI has capability to distinguish human coronary atherosclerotic plaque compositions and accurately classify advanced plaques.

  19. Investigation of in-vivo skin autofluorescence lifetimes under long-term cw optical excitation

    Energy Technology Data Exchange (ETDEWEB)

    Lihachev, A; Ferulova, I; Vasiljeva, K; Spigulis, J [Institute of Atomic Physics and Spectroscopy, University of Latvia, Riga (Latvia)

    2014-08-31

    The main results obtained during the last five years in the field of laser-excited in-vivo human skin photobleaching effects are presented. The main achievements and results obtained, as well as methods and experimental devices are briefly described. In addition, the impact of long-term 405-nm cw low-power laser excitation on the skin autofluorescence lifetime is experimentally investigated. (laser biophotonics)

  20. Two-photon excited fluorescence microscopy application for ex vivo investigation of ocular fundus samples

    Science.gov (United States)

    Peters, Sven; Hammer, Martin; Schweitzer, Dietrich

    2011-07-01

    Two-photon excited fluorescence (TPEF) imaging of ocular tissue has recently become a promising tool in ophthalmology for diagnostic and research purposes. The feasibility and the advantages of TPEF imaging, namely deeper tissue penetration and improved high-resolution imaging of microstructures, have been demonstrated lately using human ocular samples. The autofluorescence properties of endogenous fluorophores in ocular fundus tissue are well known from spectrophotometric analysis. But fluorophores, especially when it comes to fluorescence lifetime, typically display a dependence of their fluorescence properties on local environmental parameters. Hence, a more detailed investigation of ocular fundus autofluorescence ideally in vivo is of utmost interest. The aim of this study is to determine space-resolved the stationary and time-resolved fluorescence properties of endogenous fluorophores in ex vivo porcine ocular fundus samples by means of two-photon excited fluorescence spectrum and lifetime imaging microscopy (FSIM/FLIM). By our first results, we characterized the autofluorescence of individual anatomical structures of porcine retina samples excited at 760 nm. The fluorescence properties of almost all investigated retinal layers are relatively homogenous. But as previously unknown, ganglion cell bodies show a significantly shorter fluorescence lifetime compared to the adjacent mueller cells. Since all retinal layers exhibit bi-exponential autofluorescence decays, we were able to achieve a more precise characterization of fluorescence properties of endogenous fluorophores compared to a present in vivo FLIM approach by confocal scanning laser ophthalmoscope (cSLO).

  1. Microfluidic biofunctionalisation protocols to form multi-valent interactions for cell rolling and phenotype modification investigations

    KAUST Repository

    Perozziello, Gerardo

    2013-07-01

    In this study, we propose a fast, simple method to biofunctionalise microfluidic systems for cellomic investigations based on micro-fluidic protocols. Many available processes either require expensive and time-consuming protocols or are incompatible with the fabrication of microfluidic systems. Our method differs from the existing since it is applicable to an assembled system, uses few microlitres of reagents and it is based on the use of microbeads. The microbeads have specific surface moieties to link the biomolecules and couple cell receptors. Furthermore, the microbeads serve as arm spacer and offer the benefit of the multi-valent interaction. Microfluidics was adapted together with topology and biochemistry surface modifications to offer the microenvironment for cellomic studies. Based on this principle, we exploit the streptavidin-biotin interaction to couple antibodies to the biofunctionalised microfluidic environment within 5 h using 200 μL of reagents and biomolecules. We selected the antibodies able to form complexes with the MHC class I (MHC-I) molecules present on the cell membrane and involved in the immune surveillance. To test the microfluidic system, tumour cell lines (RMA) were rolled across the coupled antibodies to recognise and strip MHC-I molecules. As result, we show that cell rolling performed inside a microfluidic chamber functionalised with beads and the opportune antibody facilitate the removal of MHC class I molecules. We showed that the level of median fluorescent intensity of the MHC-I molecules is 300 for cells treated in a not biofunctionalised surface. It decreased to 275 for cells treated in a flat biofunctionalised surface and to 250 for cells treated on a surface where biofunctionalised microbeads were immobilised. The cells with reduced expression of MHC-I molecules showed, after cytotoxicity tests, susceptibility 3.5 times higher than normal cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. In Vivo Investigation of Breast Cancer Progression by Use of an Internal Control

    Directory of Open Access Journals (Sweden)

    John Baeten

    2009-03-01

    Full Text Available Optical imaging of breast cancer has been considered for detecting functional and molecular characteristics of diseases in clinical and preclinical settings. Applied to laboratory research, photonic investigations offer a highly versatile tool for preclinical imaging and drug discovery. A particular advantage of the optical method is the availability of multiple spectral bands for performing imaging. Herein, we capitalize on this feature to demonstrate how it is possible to use different wavelengths to offer internal controls and significantly improve the observation accuracy in molecular imaging applications. In particular, we show the independent in vivo detection of cysteine proteases along with tumor permeability and interstitial volume measurements using a dual-wavelength approach. To generate results with a view toward clinically geared studies, a transgenic Her2/neu mouse model that spontaneously developed mammary tumors was used. In vivo findings were validated against conventional ex vivo tests such as histology and Western blot analyses. By correcting for biodistribution parameters, the dual-wavelength method increases the accuracy of molecular observations by separating true molecular target from probe biodistribution. As such, the method is highly appropriate for molecular imaging studies where often probe delivery and target presence are not independently assessed. On the basis of these findings, we propose the dual-wavelength/normalization approach as an essential method for drug discovery and preclinical imaging studies.

  3. ChIP-nexus: a novel ChIP-exo protocol for improved detection of in vivo transcription factor binding footprints

    Science.gov (United States)

    He, Qiye; Johnston, Jeff; Zeitlinger, Julia

    2014-01-01

    Understanding how eukaryotic enhancers are bound and regulated by specific combinations of transcription factors is still a major challenge. To better map transcription factor binding genome-wide at nucleotide resolution in vivo, we have developed a robust ChIP-exo protocol called ChIP experiments with nucleotide resolution through exonuclease, unique barcode and single ligation (ChIP-nexus), which utilizes an efficient DNA self-circularization step during library preparation. Application of ChIP-nexus to four proteins—human TBP and Drosophila NFkB, Twist and Max— demonstrates that it outperforms existing ChIP protocols in resolution and specificity, pinpoints relevant binding sites within enhancers containing multiple binding motifs and allows the analysis of in vivo binding specificities. Notably, we show that Max frequently interacts with DNA sequences next to its motif, and that this binding pattern correlates with local DNA sequence features such as DNA shape. ChIP-nexus will be broadly applicable to studying in vivo transcription factor binding specificity and its relationship to cis-regulatory changes in humans and model organisms. PMID:25751057

  4. An investigation of the effect of in vivo interferences on Raman glucose measurements

    Science.gov (United States)

    Shim, Bongchu; Oh, Hyunho; Oh, Jeankun; Yang, Yongju; Ku, Yunhee; Kim, Moosub; Kim, Dami; Eum, Hyejin; Cho, Seongmoon; Miller, David R.

    2011-03-01

    Raman spectroscopy is a promising technology for noninvasive blood glucose monitoring because of its good selectivity for the glucose molecule. The low sensitivity of the Raman signal however, makes it difficult to quantify the concentration of glucose directly from the Raman spectra. To solve this, statistical methods such as PCA (principle component analysis) and PLS (partial least square) are traditionally used. These statistical methods general work very well and give highly accurate results, provided there is no interference. In the in-vivo case however, there are many interferences such as the inhomogeneity of tissue, physiological changes, and denaturation of the tissue by the light source. This study investigates the affect of in-vivo interferences on Raman glucose measurements. In this study, a high throughput dispersive Raman system was constructed with an 830nm multimode laser, a multiple conductor optical fiber bundle, and a back-illuminated CCD spectrometer. A simply phantom was devised, which was comprised of a plastic cuvette fitted with a human fingernail window and glucose doped human serum used as the sample. To test the inhomogeneity of tissue samples, different sites of the phantom were exposed to the laser. In the case of denaturation, tests were conducted under two laser power densities: low (3.7mW/mm2) and high density (110mW/mm2). To simulate the physiological change, gelatin phantoms of varied concentration were investigated. The results of the study indicate that the dominant interferers for Raman in-vivo glucose measurements are the inhomogeneity of the tissue and the denaturation by the laser power density. The next phase for this study will be the design of a high SNR Raman system which affords a low power density laser sample illumination as well as larger volumetric illumination to mitigate the effects of tissue inhomogeneity.

  5. In vivo Raman Confocal Spectroscopy in the Investigation of the Skin Barrier.

    Science.gov (United States)

    Darlenski, Razvigor; Fluhr, Joachim W

    2016-01-01

    The epidermal barrier, predominantly attributed to the stratum corneum (SC), is the outermost part of our body that comprises multiple defensive functions against exogenous attacks and the loss of body substances, e.g. water. A novel investigative method, in vivo Raman confocal spectroscopy (RCS), is employed to study the composition of the epidermal barrier and compounds penetrating the epidermis both in a space-resolved manner. By using this method, a semiquantitative analysis of skin barrier constituents can be evaluated, namely SC lipids, natural moisturizing factor components and sweat constituents. The technique enables to examine epidermal barrier impairment in experimental settings as well as the penetration of exogenous substances into the epidermis, e.g. retinol. RCS can reveal microcompositional changes in the skin barrier as a function of age. We also review the use of RCS in studying antioxidant defense components. This chapter discusses the application of in vivo RCS in the investigation of the epidermal barrier. © 2016 S. Karger AG, Basel.

  6. Integrating Structural and Functional Imaging for Computer Assisted Detection of Prostate Cancer on Multi-Protocol In Vivo 3 Tesla MRI

    Science.gov (United States)

    Viswanath, Satish; Bloch, B. Nicolas; Rosen, Mark; Chappelow, Jonathan; Toth, Robert; Rofsky, Neil; Lenkinski, Robert; Genega, Elisabeth; Kalyanpur, Arjun; Madabhushi, Anant

    2014-01-01

    Screening and detection of prostate cancer (CaP) currently lacks an image-based protocol which is reflected in the high false negative rates currently associated with blinded sextant biopsies. Multi-protocol magnetic resonance imaging (MRI) offers high resolution functional and structural data about internal body structures (such as the prostate). In this paper we present a novel comprehensive computer-aided scheme for CaP detection from high resolution in vivo multi-protocol MRI by integrating functional and structural information obtained via dynamic-contrast enhanced (DCE) and T2-weighted (T2-w) MRI, respectively. Our scheme is fully-automated and comprises (a) prostate segmentation, (b) multimodal image registration, and (c) data representation and multi-classifier modules for information fusion. Following prostate boundary segmentation via an improved active shape model, the DCE/T2-w protocols and the T2-w/ex vivo histological prostatectomy specimens are brought into alignment via a deformable, multi-attribute registration scheme. T2-w/histology alignment allows for the mapping of true CaP extent onto the in vivo MRI, which is used for training and evaluation of a multi-protocol MRI CaP classifier. The meta-classifier used is a random forest constructed by bagging multiple decision tree classifiers, each trained individually on T2-w structural, textural and DCE functional attributes. 3-fold classifier cross validation was performed using a set of 18 images derived from 6 patient datasets on a per-pixel basis. Our results show that the results of CaP detection obtained from integration of T2-w structural textural data and DCE functional data (area under the ROC curve of 0.815) significantly outperforms detection based on either of the individual modalities (0.704 (T2-w) and 0.682 (DCE)). It was also found that a meta-classifier trained directly on integrated T2-w and DCE data (data-level integration) significantly outperformed a decision-level meta

  7. Contemporary Daughter/Son Adult Social Role Performance Rating Scale and Interview Protocol: Development, Content Validation, and Exploratory Investigation

    Science.gov (United States)

    Cozad, Dana Everett

    2009-01-01

    The purpose of this study was to develop and content validate a Performance Rating Scale and Interview Protocol, enabling study of the social role performance of adult daughters and sons as they fulfill the societal norms and expectations of adult children. This exploratory investigation was one of 13 contemporary adult social roles completed by…

  8. Use of a standardized JaCVAM in vivo rat comet assay protocol to assess the genotoxicity of three coded test compounds; ampicillin trihydrate, 1,2-dimethylhydrazine dihydrochloride, and N-nitrosodimethylamine.

    Science.gov (United States)

    McNamee, J P; Bellier, P V

    2015-07-01

    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay (comet assay), our laboratory examined ampicillin trihydrate (AMP), 1,2-dimethylhydrazine dihydrochloride (DMH), and N-nitrosodimethylamine (NDA) using a standard comet assay validation protocol (v14.2) developed by the JaCVAM validation management team (VMT). Coded samples were received by our laboratory along with basic MSDS information. Solubility analysis and range-finding experiments of the coded test compounds were conducted for dose selection. Animal dosing schedules, the comet assay processing and analysis, and statistical analysis were conducted in accordance with the standard protocol. Based upon our blinded evaluation, AMP was not found to exhibit evidence of genotoxicity in either the rat liver or stomach. However, both NDA and DMH were observed to cause a significant increase in % tail DNA in the rat liver at all dose levels tested. While acute hepatoxicity was observed for these compounds in the high dose group, in the investigators opinion there were a sufficient number of consistently damaged/measurable cells at the medium and low dose groups to judge these compounds as genotoxic. There was no evidence of genotoxicity from either NDA or DMH in the rat stomach. In conclusion, our laboratory observed increased DNA damage from two blinded test compounds in rat liver (later identified as genotoxic carcinogens), while no evidence of genotoxicity was observed for the third blinded test compound (later identified as a non-genotoxic, non-carcinogen). This data supports the use of a standardized protocol of the in vivo comet assay as a cost-effective alternative genotoxicity assay for regulatory testing purposes. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  9. Ex vivo and in vivo investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in rats.

    Science.gov (United States)

    Saraswat, B; Visen, P K; Patnaik, G K; Dhawan, B N

    1999-09-01

    Picroliv, the active constituent isolated from the plant Picrorhiza kurroa, was evaluated as a hepatoprotective agent against ethanol-induced hepatic injury in rats. Alcohol feeding (3.75 g/kg x45 days) produced 20-114% alteration in selected serum (AST, ALT and ALP) and liver markers (lipid, glycogen and protein). Further, it reduced the viability (44-48%) of isolated hepatocytes (ex vivo) as assessed by Trypan blue exclusion and rate of oxygen uptake. Its effect was also seen on specific alcohol-metabolizing enzymes (aldehyde dehydrogenase, 41%; acetaldehyde dehydrogenase, 52%) in rat hepatocytes. The levels of these enzymes were found to be reduced in the cells following alcohol intoxication. Ethyl alcohol also produced cholestasis (41-53%), as indicated by reduction in bile volume, bile salts and bile acids. Picroliv treatment (3-12 mg/kg p.o. x45 days) restored the altered parameters in a dose-dependent manner (36-100%).

  10. Prion structure investigated in situ, ex vivo, and in vitro by FTIR spectroscopy

    Science.gov (United States)

    Kneipp, Janina; Miller, Lisa M.; Spassov, Sashko; Sokolowski, Fabian; Lasch, Peter; Beekes, Michael; Naumann, Dieter

    2004-07-01

    Syrian hamster nervous tissue was investigated by FTIR microspectroscopy with conventional and synchrotron infrared light sources. Various tissue structures from the cerebellum and medulla oblongata of scrapie-infected and control hamsters were investigated at a spatial resolution of 50 μm. Single neurons in dorsal root ganglia of scrapie-infected hamsters were analyzed by raster scan mapping at 6 μm spatial resolution. These measurements enabled us to (i) scrutinize structural differences between infected and non-infected tissue and (ii) analyze for the first time the distribution of different protein structures in situ within single nerve cells. Single nerve cells exhibited areas of increased β-sheet content, which co-localized consistently with accumulations of the pathological prion protein (PrPSc). Spectral data were also obtained from purified, partly proteinase K digested PrPSc isolated from scrapie-infected nervous tissue of hamsters to elucidate similarities/dissimilarities between prion structure in situ and ex vivo. A further comparison is drawn to the recombinant Syrian hamster prion protein SHaPrP90-232, whose in vitro transition from the predominantly a-helical isoform to β-sheet rich oligomeric structures was also investigated by FTIR spectroscopy.

  11. Investigating a reduced size real-time transport protocol for low-bandwidth networks

    CSIR Research Space (South Africa)

    Kakande, JN

    2011-09-01

    Full Text Available Optimization of bandwidth usage for video streaming is of paramount importance in networks where low bitrate links are typical. Among the solutions proposed to address this problem is header compression. Real-Time Transport Protocol (RTP) and RTP...

  12. Cutaneous tumors in vivo investigations using fluorescence and diffuse reflectance techniques

    Science.gov (United States)

    Borisova, E.; Troyanova, P.; Nikolova, E.; Avramov, L.

    2008-06-01

    In the recent years, there has been growing interest in the common use of laser-induced autofluorescence (LIAF) and reflectance spectroscopy (RS) to differentiate disease from normal surrounding tissue - so called optical biopsy method. Painless, instant diagnoses from optical biopsies will soon be a reality. These forms of optical diagnoses are preferable to the removal of several square millimeters of tissue surface - common in traditional biopsies - followed by delays while samples are sent for clinical analysis. The goal of this work was investigation of cutaneous benign and malignant lesions by the methods of LIAFS and RS. A nitrogen laser at 337 nm was applied for the needs of autofluorescence excitation. Broad-spectrum halogen lamp (from 400 to 900 nm) was applied for diffuse reflectance measurements. An associated microspectrometer detected in vivo the fluorescence and reflectance signals from human skin. The main spectral features of benign lesions - compound nevus, dysplastic nevi, heamangioma and basal cell papilloma and malignant lesions - pigmented, amelanotic and secondary malignant melanoma, as well as basal cell carcinoma are discussed and their possible origins are indicated. Spectra from healthy skin areas near to the lesion were detected to be used posteriori to reveal changes between healthy and lesion skin spectra. Influence of the main skin pigments on the spectra detected is discussed and evaluation of possibilities for differentiation between malignant and benign lesions is made based on their spectral properties. This research shows that non-invasive and high-sensitive in vivo detection by means of appropriate light sources and detectors should be possible, related to real-time determination of existing pathological conditions.

  13. In vivo-to-in silico iterations to investigate aeroallergen-host interactions.

    Directory of Open Access Journals (Sweden)

    Alba Llop-Guevara

    Full Text Available BACKGROUND: Allergic asthma is a complex process arising out of the interaction between the immune system and aeroallergens. Yet, the relationship between aeroallergen exposure, allergic sensitization and disease remains unclear. This knowledge is essential to gain further insight into the origin and evolution of allergic diseases. The objective of this research is to develop a computational view of the interaction between aeroallergens and the host by investigating the impact of dose and length of aeroallergen exposure on allergic sensitization and allergic disease outcomes, mainly airway inflammation and to a lesser extent lung dysfunction and airway remodeling. METHODS AND PRINCIPAL FINDINGS: BALB/C mice were exposed intranasally to a range of concentrations of the most pervasive aeroallergen worldwide, house dust mite (HDM, for up to a quarter of their lifespan (20 weeks. Actual biological data delineating the kinetics, nature and extent of responses for local (airway inflammation and systemic (HDM-specific immunoglobulins events were obtained. Mathematical equations for each outcome were developed, evaluated, refined through several iterations involving in vivo experimentation, and validated. The models accurately predicted the original biological data and simulated an extensive array of previously unknown responses, eliciting two- and three-dimensional models. Our data demonstrate the non-linearity of the relationship between aeroallergen exposure and either allergic sensitization or airway inflammation, identify thresholds, behaviours and maximal responsiveness for each outcome, and examine inter-variable relationships. CONCLUSIONS: This research provides a novel way to visualize allergic responses in vivo and establishes a basic experimental platform upon which additional variables and perturbations can be incorporated into the system.

  14. Evaluation and implementation of graded in vivo exposure for chronic low back pain in a German outpatient setting: a study protocol of a randomized controlled trial.

    Science.gov (United States)

    Riecke, Jenny; Holzapfel, Sebastian; Rief, Winfried; Glombiewski, Julia Anna

    2013-07-09

    The purpose of the present study is to introduce an adapted protocol of in vivo exposure for fear avoidant back pain patients and its implementation in the German health care system without multidisciplinary teams. Case studies demonstrated promising effects but three preceding randomized controlled trials (RCTs) could not support the former results. More empirical support is necessary to further substantiate the effectiveness of in vivo exposure. A total of 108 chronic low back pain patients are randomly assigned to one out of three conditions (A: exposure_long (15 sessions), B: exposure_short (10 sessions) or C: control condition cognitive behavioral therapy (15 sessions)). The inclusion criteria are: back pain ≥3 months and a sufficient level of fear-avoidance. An effect evaluation, a process evaluation and an economic evaluation are conducted. Primary outcomes are pain-related disability and pain intensity. Secondary outcomes are: emotional distress, fear avoidance, catastrophizing and costs. Data are collected at baseline, upon completion of the intervention, after 10 sessions, and at six months following completion of treatment. Besides the comparison of exposure in vivo and cognitive behavioral therapy (CBT), we additionally compare a short and a long version of exposure to analyze dose response effects. This is, to our knowledge, the first RCT comparing in vivo exposure to psychological treatment as usual in terms of cognitive behavioral therapy. Results will help to find out whether a tailored treatment for fear avoidant back pain patients is more effective than a general pain management treatment. The trial has been registered to ClinicalTrial.gov. The trial registration number is NCT01484418.

  15. In Vivo Investigation of ALBO-OS Scaffold Based on Hydroxyapatite and PLGA

    Directory of Open Access Journals (Sweden)

    Vukoman Jokanović

    2016-01-01

    Full Text Available A synthetic bone substitute based on calcium hydroxyapatite (CHA and poly(lactic-co-glycolic acid (PLGA, described in this paper, was synthesized to fulfill specific requirements like biodegradability, satisfying mechanical properties, optimal porosity and nanotopology, osteoinductive and osteoconductive properties, and so forth. Structural and morphological properties of the new scaffold were analyzed by micro computed tomography and scanning electron microscopy, while its physicochemical properties were investigated by X-ray diffraction and infrared spectroscopy. In vivo biological investigations of the synthesized scaffold were conducted over the cutaneous irritation and biofunctionality assays on rabbits and the test of acute systemic toxicity on mice. The results showed that the scaffold is not irritant and that it does not exhibit any symptoms of acute toxicity. Biofunctionality assays which include evaluation of the presence of various cells of immune response, the presence of neoangiogenesis, percentage of mineralization of newly formed bone, and fibroplasia in the tissue indicated that the new scaffold is suitable for the application in maxillofacial and dental surgery as a bone substitute. Also, it showed significant advantages over commercial product Geistlich Bio-Oss® from the aspect of some parameters of immunological response.

  16. Culex tarsalis vitellogenin gene promoters investigated in silico and in vivo using transgenic Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Song Chen

    Full Text Available Genetic modification, or transgenesis, is a powerful technique to investigate the molecular interactions between vector-borne pathogens and their arthropod hosts, as well as a potential novel approach for vector-borne disease control. Transgenesis requires the use of specific regulatory regions, or promoters, to drive expression of genes of interest in desired target tissues. In mosquitoes, the vast majority of described promoters are from Anopheles and Aedes mosquitoes.Culex tarsalis is one of the most important vectors of arboviruses (including West Nile virus in North America, yet it has not been the subject of molecular genetic study. In order to facilitate molecular genetic work in this important vector species, we isolated four fat body-specific promoter sequences located upstream of the Cx. tarsalis vitellogenin genes (Vg1a, Vg1b, Vg2a and Vg2b. Sequences were analyzed in silico to identify requisite cis-acting elements. The ability for promoter sequences to drive expression of green fluorescent protein (GFP in vivo was investigated using transgenic Drosophila melanogaster. All four promoters were able to drive GFP expression but there was dramatic variation between promoters and between individual Drosophila lines, indicating significant position effects. The highest expression was observed in line Vg2bL3, which was >300-fold higher than the lowest line Vg1aL2.These new promoters will be useful for driving expression of genes of interest in transgenic Cx. tarsalis and perhaps other insects.

  17. In vivo investigations on the penetration of various oils and their influence on the skin barrier.

    Science.gov (United States)

    Patzelt, A; Lademann, J; Richter, H; Darvin, M E; Schanzer, S; Thiede, G; Sterry, W; Vergou, T; Hauser, M

    2012-08-01

    The skin represents a potent barrier to the environment, which can be enhanced by the topical application of skin care products, such as oil and oil-based formulations by moisturizing the skin. The aim of this study was the investigation of the penetration behaviour of four vegetable oils and of paraffin oil into the stratum corneum by laser scanning microscopy. In addition, the occlusion capacity of these substances was assessed by transepidermal water loss (TEWL) measurements. Petrolatum served as a positive control for skin occlusion. The study was conducted in vivo and included six healthy volunteers. Paraffin oil, as well as the vegetable oils, penetrated only into the first upper layers of the stratum corneum. TEWL measurements indicated that the application of the vegetable oils (except jojoba oil) as well as paraffin oil, led to a similar occlusion of the skin surface. The most effective occlusion was found for petrolatum. For the investigated oils, a deeper penetration than into the first upper layers of the stratum corneum could be excluded. The decreased TEWL values indicate that the application of the oils leads to a semi-occlusion of the skin surface as it is intended by the use of oils to retain moisture in skin. © 2011 John Wiley & Sons A/S.

  18. A protocol for the investigation of the intracellular Staphylococcus aureus metabolome.

    Science.gov (United States)

    Meyer, Hanna; Liebeke, Manuel; Lalk, Michael

    2010-06-15

    Systems biology studies assume the acquisition of reliable and reproducible data sets. Metabolomics, in particular, requires comprehensive evaluated workflows to enable the analysis of hundreds of different compounds. Therefore, a protocol to elucidate the metabolome of the gram-positive pathogen, Staphylococcus aureus COL strain, grown in a chemically defined medium is introduced here. Different standard operating procedures in the field of metabolome experiments were tested for common pitfalls. These included suitable and fast sampling processes, efficient metabolite extraction, quenching effectiveness (energy charge), and estimation of leakage and recovery of metabolites. Moreover, a cell disruption protocol for S. aureus was developed and optimized for metabolome analyses, for the express purpose of obtaining reproducible data. We used complementary methods (e.g., gas chromatography and/or liquid chromatography coupled with mass spectrometry) to detect the highly chemically diverse groups of metabolites for a global insight into the intracellular metabolism of S. aureus. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  19. Assessing the Effectiveness of the NICHD Investigative Interview Protocol when Interviewing French-Speaking Alleged Victims of Child Sexual Abuse in Quebec

    Science.gov (United States)

    Cyr, Mireille; Lamb, Michael E.

    2009-01-01

    Objectives: The study was designed to assess the effectiveness of the flexibly structured NICHD Investigative Interview Protocol for child sexual abuse (CSA) investigative interviews by police officers and mental health workers in Quebec. The NICHD Protocol was designed to operationalize "best practice" guidelines and to help forensic…

  20. Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain.

    Science.gov (United States)

    Keevil, S F; Barbiroli, B; Brooks, J C; Cady, E B; Canese, R; Carlier, P; Collins, D J; Gilligan, P; Gobbi, G; Hennig, J; Kügel, H; Leach, M O; Metzler, D; Mlynárik, V; Moser, E; Newbold, M C; Payne, G S; Ring, P; Roberts, J N; Rowland, I J; Thiel, T; Tkác, I; Topp, S; Wittsack, H J; Podo, F

    1998-11-01

    We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.

  1. In vivo laser scanning microscopic investigation of the decontamination of hazardous substances from the human skin

    Science.gov (United States)

    Lademann, J.; Patzelt, A.; Schanzer, S.; Richter, H.; Gross, I.; Menting, K. H.; Frazier, L.; Sterry, W.; Antoniou, C.

    2010-12-01

    The stimulation of the penetration of topically applied substances into the skin is a topic of intensive dermatological and pharmacological research. In this context, it was found that in addition to the intercellular penetration, the follicular penetration also represents an efficient penetration pathway. The hair follicles act as a long-term reservoir for topically applied substances. They are surrounded by all important target structures, such as blood capillaries, stem and dendritic cells. Therefore, the hair follicles, as well as the skin, need to be protected from hazardous substances. The traditional method of decontamination after respective accidental contacts consists of an intensive washing of the skin. However, during this mechanical procedure, the substances can be pushed even deeper into the hair follicles. In the present study, absorbent materials were applied to remove a fluorescent model substance from the skin without inducing mechanical stress. The results were compared to the decontamination effects obtained by intensive washing. Investigations were performed by means of in vivo laser scanning microscopy (LSM). The comparison revealed that decontamination with absorbent materials is more effective than decontamination with washing processes.

  2. Investigation of a pulsed current annealing method in reusing MOSFET dosimeters for in vivo IMRT dosimetry.

    Science.gov (United States)

    Luo, Guang-Wen; Qi, Zhen-Yu; Deng, Xiao-Wu; Rosenfeld, Anatoly

    2014-05-01

    To explore the feasibility of pulsed current annealing in reusing metal oxide semiconductor field-effect transistor (MOSFET) dosimeters for in vivo intensity modulated radiation therapy (IMRT) dosimetry. Several MOSFETs were irradiated at d(max) using a 6 MV x-ray beam with 5 V on the gate and annealed with zero bias at room temperature. The percentage recovery of threshold voltage shift during multiple irradiation-annealing cycles was evaluated. Key dosimetry characteristics of the annealed MOSFET such as the dosimeter's sensitivity, reproducibility, dose linearity, and linearity of response within the dynamic range were investigated. The initial results of using the annealed MOSFETs for IMRT dosimetry practice were also presented. More than 95% of threshold voltage shift can be recovered after 24-pulse current continuous annealing in 16 min. The mean sensitivity degradation was found to be 1.28%, ranging from 1.17% to 1.52%, during multiple annealing procedures. Other important characteristics of the annealed MOSFET remained nearly consistent before and after annealing. Our results showed there was no statistically significant difference between the annealed MOSFETs and their control samples in absolute dose measurements for IMRT QA (p = 0.99). The MOSFET measurements agreed with the ion chamber results on an average of 0.16% ± 0.64%. Pulsed current annealing provides a practical option for reusing MOSFETs to extend their operational lifetime. The current annealing circuit can be integrated into the reader, making the annealing procedure fully automatic.

  3. A protocol for the differentiation of human embryonic stem cells into dopaminergic neurons using only chemically defined human additives: Studies in vitro and in vivo.

    Science.gov (United States)

    Iacovitti, Lorraine; Donaldson, Angela E; Marshall, Cheryl E; Suon, Sokreine; Yang, Ming

    2007-01-05

    Our ability to use human embryonic stem (hES) cells in cell replacement therapy for Parkinson's disease depends on the discovery of ways to simply and reliably differentiate a dopaminergic (DA) phenotype in these cells. Although several protocols exist for the differentiation of DA traits in hES, they involve the prolonged use of complex media with undefined components, cell conditioned media and/or co-culture with various cells, usually of animal origin. In this study, several well-characterized (H9, BG01) and several new uncharacterized (HUES7, HUES8) hES cell lines were studied for their capacity to differentiate into DA neurons in culture using a novel rapid protocol which uses only chemically-defined human-derived media additives and substrata. Within 3 weeks, cells from all 4 cell lines progressed from the undifferentiated state to beta-tubulin III positive cells expressing DA markers in vitro. Moreover, transplantation of these cells into the striata of 6-hydroxydopamine-treated rats at the neuronal progenitor stage resulted in the appearance of differentiated DA traits in vivo 2-3 weeks later.

  4. Young investigator challenge: Validation and optimization of immunohistochemistry protocols for use on cellient cell block specimens.

    Science.gov (United States)

    Sauter, Jennifer L; Grogg, Karen L; Vrana, Julie A; Law, Mark E; Halvorson, Jennifer L; Henry, Michael R

    2016-02-01

    The objective of the current study was to establish a process for validating immunohistochemistry (IHC) protocols for use on the Cellient cell block (CCB) system. Thirty antibodies were initially tested on CCBs using IHC protocols previously validated on formalin-fixed, paraffin-embedded tissue (FFPE). Cytology samples were split to generate thrombin cell blocks (TCB) and CCBs. IHC was performed in parallel. Antibody immunoreactivity was scored, and concordance or discordance in immunoreactivity between the TCBs and CCBs for each sample was determined. Criteria for validation of an antibody were defined as concordant staining in expected positive and negative cells, in at least 5 samples each, and concordance in at least 90% of the samples total. Antibodies that failed initial validation were retested after alterations in IHC conditions. Thirteen of the 30 antibodies (43%) did not meet initial validation criteria. Of those, 8 antibodies (calretinin, clusters of differentiation [CD] 3, CD20, CDX2, cytokeratin 20, estrogen receptor, MOC-31, and p16) were optimized for CCBs and subsequently validated. Despite several alterations in conditions, 3 antibodies (Ber-EP4, D2-40, and paired box gene 8 [PAX8]) were not successfully validated. Nearly one-half of the antibodies tested in the current study failed initial validation using IHC conditions that were established in the study laboratory for FFPE material. Although some antibodies subsequently met validation criteria after optimization of conditions, a few continued to demonstrate inadequate immunoreactivity. These findings emphasize the importance of validating IHC protocols for methanol-fixed tissue before clinical use and suggest that optimization for alcohol fixation may be needed to obtain adequate immunoreactivity on CCBs. © 2016 American Cancer Society.

  5. Investigating Linguistic Sources of Differential Item Functioning Using Expert Think-Aloud Protocols in Science Achievement Tests

    Science.gov (United States)

    Roth, Wolff-Michael; Oliveri, Maria Elena; Dallie Sandilands, Debra; Lyons-Thomas, Juliette; Ercikan, Kadriye

    2013-03-01

    Even if national and international assessments are designed to be comparable, subsequent psychometric analyses often reveal differential item functioning (DIF). Central to achieving comparability is to examine the presence of DIF, and if DIF is found, to investigate its sources to ensure differentially functioning items that do not lead to bias. In this study, sources of DIF were examined using think-aloud protocols. The think-aloud protocols of expert reviewers were conducted for comparing the English and French versions of 40 items previously identified as DIF (N = 20) and non-DIF (N = 20). Three highly trained and experienced experts in verifying and accepting/rejecting multi-lingual versions of curriculum and testing materials for government purposes participated in this study. Although there is a considerable amount of agreement in the identification of differentially functioning items, experts do not consistently identify and distinguish DIF and non-DIF items. Our analyses of the think-aloud protocols identified particular linguistic, general pedagogical, content-related, and cognitive factors related to sources of DIF. Implications are provided for the process of arriving at the identification of DIF, prior to the actual administration of tests at national and international levels.

  6. A Monte Carlo investigation of contaminant electrons due to a novel in vivo transmission detector.

    Science.gov (United States)

    Asuni, G; Jensen, J M; McCurdy, B M C

    2011-02-21

    A novel transmission detector (IBA Dosimetry, Germany) developed as an IMRT quality assurance tool, intended for in vivo patient dose measurements, is studied here. The goal of this investigation is to use Monte Carlo techniques to characterize treatment beam parameters in the presence of the detector and to compare to those of a plastic block tray (a frequently used clinical device). Particular attention is paid to the impact of the detector on electron contamination model parameters of two commercial dose calculation algorithms. The linac head together with the COMPASS transmission detector (TRD) was modeled using BEAMnrc code. To understand the effect of the TRD on treatment beams, the contaminant electron fluence, energy spectra, and angular distributions at different SSDs were analyzed for open and non-open (i.e. TRD and block tray) fields. Contaminant electrons in the BEAMnrc simulations were separated according to where they were created. Calculation of surface dose and the evaluation of contributions from contaminant electrons were performed using the DOSXYZnrc user code. The effect of the TRD on contaminant electrons model parameters in Eclipse AAA and Pinnacle(3) dose calculation algorithms was investigated. Comparisons of the fluence of contaminant electrons produced in the non-open fields versus open field show that electrons created in the non-open fields increase at shorter SSD, but most of the electrons at shorter SSD are of low energy with large angular spread. These electrons are out-scattered or absorbed in air and contribute less to surface dose at larger SSD. Calculated surface doses with the block tray are higher than those with the TRD. Contribution of contaminant electrons to dose in the buildup region increases with increasing field size. The additional contribution of electrons to surface dose increases with field size for TRD and block tray. The introduction of the TRD results in a 12% and 15% increase in the Gaussian widths used in the

  7. In vivo and in silico investigation of selected herbal compounds as ...

    African Journals Online (AJOL)

    against the Mycobacterium tuberculosis (Mtb) H37v strain by determining their microbial inhibitory concentration (MIC) and cytotoxicity. The compounds were also screened using in silico techniques, such as molecular docking and absorption, distribution, metabolism, and excretion (ADME) prediction. Results: The in vivo ...

  8. Toward a standardized investigation protocol in sudden unexpected deaths in infancy in South Africa: a multicenter study of medico-legal investigation procedures and outcomes.

    Science.gov (United States)

    du Toit-Prinsloo, Lorraine; Dempers, Johan; Verster, Janette; Hattingh, Christa; Nel, Hestelle; Brandt, V D; Jordaan, Joyce; Saayman, Gert

    2013-09-01

    South Africa manifests a socio-economic dichotomy that shows features of both a developed and developing country. As a result of this, areas exist where a lack of resources and expertise prevents the implementation of a highly standardized protocol for the investigation of sudden and unexpected deaths in infants (SUDI). Although the medico-legal mortuaries attached to academic centers have the capacity to implement standardized protocols, a previous study conducted at two large medico-legal mortuaries indicated otherwise. This study also revealed that the exact number and incidence of sudden infant death syndrome (SIDS) cases was unknown. These findings prompted a multicenter study of the medico-legal investigation procedures and outcomes in five academic centers in South Africa. A retrospective case audit was conducted for a 5-year period (2005-2009) at medico-legal laboratories attached to universities in Bloemfontein, Cape Town-Tygerberg, Durban, Johannesburg, and Pretoria. The total case load as well as the total number of infants younger than 1 year of age admitted to these mortuaries was documented. The case files on all infants younger than 1 year of age who were admitted as sudden and unexpected or unexplained deaths were included in the study population. Data collected on the target population included demographic details, the nature and scope of the post-mortem examinations, as well as the final outcome (cause of death). A total case load of 80,399 cases were admitted to the mortuaries over the 5 year period with a total of 3,295 (6.5 %) infants. In the infant group, 591 (0.7 %) died from non-natural causes and 2,704 (3.3 %) cases of sudden, unexpected and/or unexplained deaths in infants were admitted and included in the detailed case analysis study. One hundred and ninety-nine babies were between 0 and 7 days of age and 210 babies between 8 and 30 days. The remaining 2,295 infants were between 1 month and 12 months of age. Death scene investigation was

  9. On Designing Thermal-Aware Localized QoS Routing Protocol for in-vivo Sensor Nodes in Wireless Body Area Networks.

    Science.gov (United States)

    Monowar, Muhammad Mostafa; Bajaber, Fuad

    2015-06-15

    In this paper, we address the thermal rise and Quality-of-Service (QoS) provisioning issue for an intra-body Wireless Body Area Network (WBAN) having in-vivo sensor nodes. We propose a thermal-aware QoS routing protocol, called TLQoS, that facilitates the system in achieving desired QoS in terms of delay and reliability for diverse traffic types, as well as avoids the formation of highly heated nodes known as hotspot(s), and keeps the temperature rise along the network to an acceptable level. TLQoS exploits modular architecture wherein different modules perform integrated operations in providing multiple QoS service with lower temperature rise. To address the challenges of highly dynamic wireless environment inside the human body. TLQoS implements potential-based localized routing that requires only local neighborhood information. TLQoS avoids routing loop formation as well as reduces the number of hop traversal exploiting hybrid potential, and tuning a configurable parameter. We perform extensive simulations of TLQoS, and the results show that TLQoS has significant performance improvements over state-of-the-art approaches.

  10. In Vitro and In Vivo Investigation of the Potential of Amorphous Microporous Silica as a Protein Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Amol Chaudhari

    2013-01-01

    Full Text Available Delivering growth factors (GFs at bone/implant interface needs to be optimized to achieve faster osseointegration. Amorphous microporous silica (AMS has a potential to be used as a carrier and delivery platform for GFs. In this work, adsorption (loading and release (delivery mechanism of a model protein, bovine serum albumin (BSA, from AMS was investigated in vitro as well as in vivo. In general, strong BSA adsorption to AMS was observed. The interaction was stronger at lower pH owing to favorable electrostatic interaction. In vitro evaluation of BSA release revealed a peculiar release profile, involving a burst release followed by a 6 h period without appreciable BSA release and a further slower release later. Experimental data supporting this observation are discussed. Apart from understanding protein/biomaterial (BSA/AMS interaction, determination of in vivo protein release is an essential aspect of the evaluation of a protein delivery system. In this regard micropositron emission tomography (μ-PET was used in an exploratory experiment to determine in vivo BSA release profile from AMS. Results suggest stronger in vivo retention of BSA when adsorbed on AMS. This study highlights the possible use of AMS as a controlled protein delivery platform which may facilitate osseointegration.

  11. Study protocol: a randomized controlled trial investigating the effects of a psychosexual training program for adolescents with autism spectrum disorder.

    Science.gov (United States)

    Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka T; Verhulst, Frank C; Maras, Athanasios; van der Vegt, Esther J M

    2015-08-28

    Previous research shows that adolescents with autism spectrum disorder (ASD) run several risks in their psychosexual development and that these adolescents can have limited access to reliable information on puberty and sexuality, emphasizing the need for specific guidance of adolescents with ASD in their psychosexual development. Few studies have investigated the effects of psychosexual training programs for adolescents with ASD and to date no randomized controlled trials are available to study the effects of psychosexual interventions for this target group. The randomized controlled trial (RCT) described in this study protocol aims to investigate the effects of the Tackling Teenage Training (TTT) program on the psychosexual development of adolescents with ASD. This parallel clinical trial, conducted in the South-West of the Netherlands, has a simple equal randomization design with an intervention and a waiting-list control condition. Two hundred adolescents and their parents participate in this study. We assess the participants in both conditions using self-report as well as parent-report questionnaires at three time points during 1 year: at baseline (T1), post-treatment (T2), and for follow-up (T3). To our knowledge, the current study is the first that uses a randomized controlled design to study the effects of a psychosexual training program for adolescents with ASD. It has a number of methodological strengths, namely a large sample size, a wide range of functionally relevant outcome measures, the use of multiple informants, and a standardized research and intervention protocol. Also some limitations of the described study are identified, for instance not making a comparison between two treatment conditions, and no use of blinded observational measures to investigate the ecological validity of the research results. Dutch Trial Register NTR2860. Registered on 20 April 2011.

  12. Egg albumin microspheres containing paracetamol for oral administration. II. In vivo investigation.

    Science.gov (United States)

    Torrado, J J; Illum, L; Cadorniga, R; Davis, S S

    1990-01-01

    Egg albumin microspheres containing paracetamol for oral administration were prepared and their in vivo characteristics evaluated. The egg albumin microspheres were able to improve the organoleptic characteristics of paracetamol formulations. The pharmacokinetic characteristics of three different formulations of paracetamol were evaluated in six volunteers. The formulations administered orally were: (1) Paracetamol granulated with lactose (reference), (2) Egg albumin microspheres and (3) Egg albumin microspheres coated with polymethacrylate. The pharmacokinetic characteristics for formulations 1 and 2 were similar but formulation 3 gave significant differences (p less than 0.05) in Ka, Cmax and tmax. No significant differences in relative bioavailability were observed.

  13. Per-protocol investigation of a best practice exercise referral scheme.

    Science.gov (United States)

    Stewart, L; Dolan, E; Carver, P; Swinton, P A

    2017-09-01

    To investigate the effects of an exercise referral scheme (ERS) aligned to the UK best practice guidelines on a range of outcomes including those associated with key health concerns of the Scottish population. A longitudinal design with data collection at three time points (baseline, midway and post) during a 12-week ERS intervention was employed. Health-related physical fitness was assessed through measurement of resting heart rate, blood pressure, FEV1:FEV6 (ratio of forced expiratory volume over one [FEV1] and six [FEV6] seconds), body mass and peak oxygen uptake (VO2 peak), whilst functional capacity was assessed through the five times sit to stand test. Psychosocial well-being and quality of life were measured using the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and the Profile of Mood State questionnaires. Growth curve analyses were used to model each outcome variable across the three time periods. A range of effects were obtained with significant linear improvements in physical performance tests (P time were obtained for body composition variables and physical activity levels (P best practice guidelines can positively influence a range of health outcomes including those associated with lung function and cardiovascular fitness which are prevalent medical conditions in Scotland. In addition, results indicate that ERS can positively affect outcomes related to functional capacity as well as mental well-being and perceptions of health. The findings of the study identify the need for further investigation including consideration of the initial health status of referred clients. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  14. Isolation of hydroxytyrosol from olive leaves extract, radioiodination and investigation of bioaffinity using in vivo/in vitro methods

    Energy Technology Data Exchange (ETDEWEB)

    Ozkan, M.; Biber Muftuler, F.Z.; Kilcar, A. Yurt; Medine, E.I.; Unak, P. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2013-11-01

    It is known that medicinal plants like olive have biological activities due to their flavonoid content such as olueropein, tyrosol, hydroxytyrosol etc. In current study, hydroxytrosol (HT) which is one of the major phenolic compounds in olive, olive leaves and olive oil, was isolated after methanol extraction and purification of olive leaves which are grown in the northern Anatolia region of Turkey. The isolated HT was radiolabeled with {sup 131}I ({sup 131}I-HT) and the bioaffinity of this radiolabeled component of olive leaves extract was investigated by using in vivo/in vitro methods. It was found that HT could be radiolabeled with {sup 131}I in yields of 95.6 {+-} 4.4% (n = 8), and in vivo studies showed that {sup 131}I-HT is taken up by urinary bladder, stomach, small intestine, large intestine, breast and prostate. Significant incorporation of activity was observed in cell lines via in vitro studies. (orig.)

  15. Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets.

    Science.gov (United States)

    Nyman, Lara R; Wells, K Sam; Head, W Steve; McCaughey, Michael; Ford, Eric; Brissova, Marcela; Piston, David W; Powers, Alvin C

    2008-11-01

    The pancreatic islets of Langerhans are highly vascularized micro-organs that play a key role in the regulation of blood glucose homeostasis. The specific arrangement of endocrine cell types in islets suggests a coupling between morphology and function within the islet. Here, we established a line-scanning confocal microscopy approach to examine the relationship between blood flow and islet cell type arrangement by real-time in vivo imaging of intra-islet blood flow in mice. These data were used to reconstruct the in vivo 3D architecture of the islet and time-resolved blood flow patterns throughout the islet vascular bed. The results revealed 2 predominant blood flow patterns in mouse islets: inner-to-outer, in which blood perfuses the core of beta cells before the islet perimeter of non-beta cells, and top-to-bottom, in which blood perfuses the islet from one side to the other regardless of cell type. Our approach included both millisecond temporal resolution and submicron spatial resolution, allowing for real-time imaging of islet blood flow within the living mouse, which has not to our knowledge been attainable by other methods.

  16. Investigating in vivo airway wall mechanics during tidal breathing with optical coherence tomography

    Science.gov (United States)

    Robertson, Claire; Lee, Sang-Won; Ahn, Yeh-Chan; Mahon, Sari; Chen, Zhongping; Brenner, Matthew; George, Steven C.

    2011-10-01

    Optical coherence tomography (OCT) is a nondestructive imaging technique offering high temporal and spatial resolution, which makes it a natural choice for assessing tissue mechanical properties. We have developed methods to mechanically analyze the compliance of the rabbit trachea in vivo using tissue deformations induced by tidal breathing, offering a unique tool to assess the behavior of the airways during their normal function. Four-hundred images were acquired during tidal breathing with a custom-built endoscopic OCT system. The surface of the tissue was extracted from a set of these images via image processing algorithms, filtered with a bandpass filter set at respiration frequency to remove cardiac and probe motion, and compared to ventilatory pressure to calculate wall compliance. These algorithms were tested on elastic phantoms to establish reliability and reproducibility. The mean tracheal wall compliance (in five animals) was 1.3+/-0.3×10-5 (mm Pa)-1. Unlike previous work evaluating airway mechanics, this new method is applicable in vivo, noncontact, and loads the trachea in a physiological manner. The technique may have applications in assessing airway mechanics in diseases such as asthma that are characterized by significant airway remodeling.

  17. Establishment of Larval Zebrafish as an Animal Model to Investigate Trypanosoma cruzi Motility In Vivo.

    Science.gov (United States)

    Akle, Veronica; Agudelo-Dueñas, Nathalie; Molina-Rodriguez, Maria A; Kartchner, Laurel Brianne; Ruth, Annette Marie; González, John M; Forero-Shelton, Manu

    2017-09-30

    Chagas disease is a parasitic infection caused by Trypanosoma cruzi, whose motility is not only important for localization, but also for cellular binding and invasion. Current animal models for the study of T. cruzi allow limited observation of parasites in vivo, representing a challenge for understanding parasite behavior during the initial stages of infection in humans. This protozoan has a flagellar stage in both vector and mammalian hosts, but there are no studies describing its motility in vivo.The objective of this project was to establish a live vertebrate zebrafish model to evaluate T. cruzi motility in the vascular system. Transparent zebrafish larvae were injected with fluorescently labeled trypomastigotes and observed using light sheet fluorescence microscopy (LSFM), a noninvasive method to visualize live organisms with high optical resolution. The parasites could be visualized for extended periods of time due to this technique's relatively low risk of photodamage compared to confocal or epifluorescence microscopy. T. cruzi parasites were observed traveling in the circulatory system of live zebrafish in different-sized blood vessels and the yolk. They could also be seen attached to the yolk sac wall and to the atrioventricular valve despite the strong forces associated with heart contractions. LSFM of T. cruzi-inoculated zebrafish larvae is a valuable method that can be used to visualize circulating parasites and evaluate their tropism, migration patterns, and motility in the dynamic environment of the cardiovascular system of a live animal.

  18. An investigation on in vitro and in vivo antimicrobial properties of the antidepressant: amitriptyline hydrochloride

    Directory of Open Access Journals (Sweden)

    Anurup Mandal

    2010-10-01

    Full Text Available The antidepressant drug amitriptyline hydrochloride was obtained in a dry powder form and was screened against 253 strains of bacteria which included 72 Gram positive and 181 Gram negative bacteria and against 5 fungal strains. The minimum inhibitory concentration (MIC was determined by inoculating a loopful of an overnight peptone water culture of the organism on nutrient agar plates containing increasing concentrations of amitriptyline hydrochloride (0, 10 µg/mL, 25 µg/mL, 50 µg/mL, 100 µg/mL, 200 µg/mL. Amitriptyline hydrochloride exhibited significant action against both Gram positive and Gram negative bacteria at 25-200 µg/mL. In the in vivo studies it was seen that amitriptyline hydrochloride at a concentration of 25 µg/g and 30 µg/g body weight of mouse offered significant protection to Swiss strain of white mice when challenged with 50 median lethal dose (MLD of a virulent strain of Salmonella typhimurium NCTC 74. The in vivo data were highly significant (p<0.001 according to the chi-square test.

  19. Pilot Study: Colostomy and Urine Collection Protocol for Investigating Potential Inciting Causes of Hen Diuresis Syndrome.

    Science.gov (United States)

    Jones, Kelli; Turner, Bradley; Brandão, João; Hubbard, Sue Ann; Magee, Danny; Baughman, Brittany; Wills, Robert; Tully, Thomas

    2015-06-01

    Hen diuresis syndrome has emerged over the past 5 yr as a significant cause of mortality in the U.S. broiler breeder industry. The condition affects hens in production and is characterized by transient muscle weakness in the vent region, transient diuresis, and often urate deposits on the skin below the vent. Affected hens are often seen straining to lay an egg, which suggests oviduct contraction is also impaired. Related hen mortality, often reaching 1% or more a week, is believed to be primarily the result of male aggression of the vent region (Turner et al., "Investigating Causes of Excessive Urate Production in Broiler Breeder Hens Associated with Peritonitis and Cannibalism Mortality," Oral Presentation at The American Association of Avian Pathologists Annual Meeting, p. 139, 2010). The exact association between the cause of mortality and this syndrome is unknown, but it may be the consequence of transient partial to full oviduct prolapse, which predisposes or stimulates cannibalism and aggression. Based on unpublished work done prior to this study (Turner et al., ibid.), the evidence suggests the underlying problem is metabolic. We feel that urine collection and analysis is an essential component to understanding this condition. This study serves as a pilot study for future investigations that attempt to identify the nature and cause of the metabolic disturbance through paired urine and serum collection and analysis. For the purpose of this study, a small sample of 10 affected and 10 unaffected birds was used for sample collection. In order to collect pure urine, the birds were surgically colostomized. Colostomy did prove to be a useful means of collecting urine free of feces, and for the purposes of our study it yielded adequate urine samples for analysis. There were statistically relevant urine values observed. Affected birds had a higher presence of blood in the urine, a lower uric acid excretion rate (mg/hr), higher concentration (mEq/L) of urine Na+, and

  20. Prolonged Helium Postconditioning Protocols during Early Reperfusion Do Not Induce Cardioprotection in the Rat Heart In Vivo: Role of Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Gezina Tanya Mei Ling Oei

    2015-01-01

    Full Text Available Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg and diazepam (1.5 mg/kg. Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3 and interleukin-1 beta (IL-1β were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6, and tumor necrosis factor alpha (TNF-α in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

  1. Prolonged helium postconditioning protocols during early reperfusion do not induce cardioprotection in the rat heart in vivo: role of inflammatory cytokines.

    Science.gov (United States)

    Oei, Gezina Tanya Mei Ling; Aslami, Hamid; Kerindongo, Raphaela Priscilla; Steenstra, Renske Johanna; Beurskens, Charlotte Jacqueline Peter; Tuip-de Boer, Anita Maria; Juffermans, Nicole Petra; Hollmann, Markus Werner; Preckel, Benedikt; Weber, Nina Claudia

    2015-01-01

    Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg) and diazepam (1.5 mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3) and interleukin-1 beta (IL-1β) were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

  2. A retrospective cohort study to investigate fatigue, psychological or cognitive impairment after TIA: protocol paper.

    Science.gov (United States)

    Moran, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Marshall, Tom

    2015-05-03

    Transient ischaemic attack (TIA) is defined by short-lasting, stroke-like symptoms, and is recognised as a medical emergency. Symptoms are assumed to completely resolve, and treatment is focused on secondary stroke/TIA prevention. However, evidence suggests that patients with TIA may experience ongoing residual impairments, which they do not receive therapy for as standard practice. TIA-induced sequelae could impact on patients' quality of life and ability to return to work or social activities. We aim to investigate whether TIA is associated with subsequent consultation for fatigue, psychological or cognitive impairment in primary care. A retrospective open cohort study of patients with first-ever TIA and matched controls. Relevant data will be extracted from The Health Improvement Network (THIN) database, an anonymised primary care database which includes data for over 12 million patients and covers approximately 6% of the UK population. Outcomes will be the first consultation for fatigue, anxiety, depression, post-traumatic stress disorder or cognitive impairment. Principal analysis will use Kaplan-Meier survivor functions to estimate time to first consultation, with log-rank tests to compare TIA and control patients. Cox proportional hazard models will predict the effect of demographic and patient characteristics on time to first consultation. Approval was granted by a THIN Scientific Review Committee (ref: 14-008). The study's findings will be published in a peer-reviewed journal and disseminated at national and international conferences and through social media. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. In vivo protocol for testing efficacy of hand-washing agents against viruses and bacteria: experiments with rotavirus and Escherichia coli.

    Science.gov (United States)

    Ansari, S A; Sattar, S A; Springthorpe, V S; Wells, G A; Tostowaryk, W

    1989-01-01

    Ten antiseptic formulations, an unmedicated liquid soap, and tap water alone were compared for their capacities to eliminate human rotavirus from the finger pads of adult volunteers; three of the antiseptics, the soap, and the tap water alone were also tested against Escherichia coli. A fecal suspension of virus or bacterium was placed on each finger pad and air dried. The contaminated site was exposed to the test product for 10 s, rinsed in tap water, and dried on a paper towel. The residual virus or bacterium was then eluted. Selected agents were also tested by an analogous whole-hand method by which the entire palm surfaces of both hands were contaminated. Alcohols (70%) alone or with Savlon reduced the virus titer by greater than 99%, whereas the reductions by Proviodine, Dettol, and Hibisol ranged from 95 to 97%. Aqueous solutions of chlorhexidine gluconate were significantly less effective for virus removal or inactivation than 70% alcohol solutions. Furthermore, Savlon in water (1:200) was found to be much less effective in eliminating the virus (80.6%) than the bacterium (98.9%). The tap water alone and the soap reduced the virus titers by 83.6 and 72.5% and the bacterial titers by 90 and 68.7%, respectively. The results of the whole-hand method agreed well with those of the finger pad protocol. We conclude that the finger pad method is a suitable model for testing the in vivo efficacy of hand-washing agents and emphasize the need for using appropriate test viruses and bacteria. PMID:2559658

  4. Blood vector velocity estimation using an autocorrelation approach: In vivo Investigation

    DEFF Research Database (Denmark)

    Udesen, Jesper; Bachmann, Michael; Rue, Kristina

    2005-01-01

    In conventional techniques for blood velocity estimation, only the axial component of the velocity vector is found. We have previously shown that it is possible to estimate the 2-D blood velocity vector both in simulations and in flow phantom experiments using a fast and inexpensive method (the...... deg phase shift in the lateral direction. The TO method works at angles where conventional methods fails to estimate any blood movement, i.e. when the angle between the ultrasound beam and the velocity vector is approximately 90 deg. In this paper the first in-vivo color flow map (CFM) images......) The common carotid artery, 2) the common carotid artery and the jugular vein, 3) the bifurcation of the common carotid artery. In all three cases the angle between the ultrasound beams and the blood velocity vector is larger than 60 deg. i.e. the conventional Doppler velocity estimator degrades significantly...

  5. In vivo multiphoton imaging of a diverse array of fluorophores to investigate deep neurovascular structure.

    Science.gov (United States)

    Miller, David R; Hassan, Ahmed M; Jarrett, Jeremy W; Medina, Flor A; Perillo, Evan P; Hagan, Kristen; Shams Kazmi, S M; Clark, Taylor A; Sullender, Colin T; Jones, Theresa A; Zemelman, Boris V; Dunn, Andrew K

    2017-07-01

    We perform high-resolution, non-invasive, in vivo deep-tissue imaging of the mouse neocortex using multiphoton microscopy with a high repetition rate optical parametric amplifier laser source tunable between λ=1,100 and 1,400 nm. By combining the high repetition rate (511 kHz) and high pulse energy (400 nJ) of our amplifier laser system, we demonstrate imaging of vasculature labeled with Texas Red and Indocyanine Green, and neurons expressing tdTomato and yellow fluorescent protein. We measure the blood flow speed of a single capillary at a depth of 1.2 mm, and image vasculature to a depth of 1.53 mm with fine axial steps (5 μm) and reasonable acquisition times. The high image quality enabled analysis of vascular morphology at depths to 1.45 mm.

  6. In Vivo Investigation of Escitalopram’s Allosteric Site on the Serotonin Transporter

    Science.gov (United States)

    Murray, Karen E.; Ressler, Kerry J.; Owens, Michael J.

    2015-01-01

    Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram’s kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10–30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p = 0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose of escitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p = 0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects. PMID:26621784

  7. Nucleus pulposus deformation in response to lumbar spine lateral flexion: an in vivo MRI investigation.

    Science.gov (United States)

    Fazey, Peter J; Takasaki, Hiroshi; Singer, Kevin P

    2010-07-01

    Whilst there are numerous studies examining aspects of sagittal plane motion in the lumbar spine, few consider coronal plane range of motion and there are no in vivo reports of nucleus pulposus (NP) displacement in lateral flexion. This study quantified in vivo NP deformation in response to side flexion in healthy volunteers. Concomitant lateral flexion and axial rotation range were also examined to evaluate the direction and extent of NP deformation. Axial T2- and coronal T1-weighted magnetic resonance images (MRI) were obtained from 21 subjects (mean age, 24.8 years) from L1 to S1 in the neutral and left laterally flexed position. Images were evaluated for intersegmental ranges of lateral flexion and axial rotation. A novel methodology derived linear pixel samples across the width of the disc from T2 images, from which the magnitude and direction of displacement of the NP was determined. This profiling technique represented the relative hydration pattern within the disc. The NP was displaced away from the direction of lateral flexion in 95/105 discs (p < 0.001). The extent of NP displacement was associated strongly with lateral flexion at L2-3 (p < 0.01). The greatest range of lateral flexion occurred at L2-3, L3-4 and L4-5. Small intersegmental ranges of axial rotation occurred at all levels, but were not associated with NP displacement. The direction of NP deformation was highly predictable in laterally flexed healthy lumbar spines; however, the magnitude of displacement was not consistent with the degree of intersegmental lateral flexion or rotation.

  8. The ability of human periodontium-derived stem cells to regenerate periodontal tissues: a preliminary in vivo investigation.

    Science.gov (United States)

    Grimm, Wolf-Dieter; Dannan, Aous; Becher, Sebastian; Gassmann, Georg; Arnold, Wolfgang; Varga, Gabor; Dittmar, Thomas

    2011-01-01

    Periodontium-derived stem cells (pdSCs) can be cultured as dentospheres and differentiated into various cells of the neuronal lineage such as glial cells, thereby demonstrating their stem cell state. This study investigated whether pdSCs could be differentiated into the osteogenic lineage and, if so, whether these cells are able to regenerate periodontal tissue in vivo in an athymic rat model. Human adult pdSCs were isolated during minimally invasive periodontal surgery and expanded in vitro. To induce osteogenic differentiation, expanded pdSCs were cultured for 3 weeks in osteogenic differentiation media. Staining for alkaline phosphatase expression was positive, suggesting osteogenic differentiation. For in vivo studies, pdSCs were delivered onto suitable collagen sponges and implanted into periodontal defects on the right buccal cortex of the mandible in 16 immunodeficient nude rats. Histologic analysis of samples from the test side revealed reformation of periodontal ligament-like tissue, collagen fibers, and elements of bone, but no functional periodontal tissue regeneration. The data show that human adult pdSCs are capable of regenerating elements of bone and collagen fibers in an in vivo animal model.

  9. Investigation of anticancer potential of hypophyllanthin and phyllanthin against breast cancer by in vitro and in vivo methods

    Directory of Open Access Journals (Sweden)

    Madhukiran Parvathaneni

    2014-02-01

    Full Text Available Objective: To investigate the in vitro and in vivo anticancer activities of hypophyllanthin and phyllanthin isolated from Phyllanthus amarus Schum & Thonn against breast cancer. Methods: In vitro anticancer activity was evaluated against two cell lines (MCF-7 and MDAMB-231 using MTT assay. In vivo anticancer activity was tested using Sprague-Dawley rats with N-methyl-N-nitrosourea induced mammary cancer. Results: In vitro studies demonstrated a dose-dependent inhibitory effect on cell growth with IC50 values of (35.18依1.48 µg/mL (hypophyllanthin and (32.51依0.95 µg/mL (phyllanthin for MCF-7; (38.74 依1.24 (hypophyllanthin and (32.2依1.17 (phyllanthin for MDA-MB-231 breast cancer cell lines. Tumor weights per group at doses of 5 and 10 mg/kg/day for hypophyllanthin (12.82 and 12.06 g and phyllanthin (11.95 and 8.87 g treated groups were significantly (P<0.001 lower than untreated N-methyl-N-nitrosourea group (35.85. Conclusions: Results of the present research work indicated that the isolated lignan compounds, hypophyllanthin and phyllanthin showed significant anticancer activities against breast cancer, in vitro and in vivo.

  10. An Investigation into the Prediction of in Vivo Clearance for a Range of Flavin-containing Monooxygenase Substrates.

    Science.gov (United States)

    Jones, Barry C; Srivastava, Abhishek; Colclough, Nicola; Wilson, Joanne; Reddy, Venkatesh Pilla; Amberntsson, Sara; Li, Danxi

    2017-10-01

    Flavin-containing monooxygenases (FMO) are metabolic enzymes mediating the oxygenation of nucleophilic atoms such as nitrogen, sulfur, phosphorus, and selenium. These enzymes share similar properties to the cytochrome P450 system but can be differentiated through heat inactivation and selective substrate inhibition by methimazole. This study investigated 10 compounds with varying degrees of FMO involvement to determine the nature of the correlation between human in vitro and in vivo unbound intrinsic clearance. To confirm and quantify the extent of FMO involvement six of the compounds were investigated in human liver microsomal (HLM) in vitro assays using heat inactivation and methimazole substrate inhibition. Under these conditions FMO contribution varied from 21% (imipramine) to 96% (itopride). Human hepatocyte and HLM intrinsic clearance (CLint) data were scaled using standard methods to determine the predicted unbound intrinsic clearance (predicted CLint u) for each compound. This was compared with observed unbound intrinsic clearance (observed CLint u) values back calculated from human pharmacokinetic studies. A good correlation was observed between the predicted and observed CLint u using hepatocytes (R(2) = 0.69), with 8 of the 10 compounds investigated within or close to a factor of 2. For HLM the in vitro-in vivo correlation was maintained (R(2) = 0.84) but the accuracy was reduced with only 3 out of 10 compounds falling within, or close to, twofold. This study demonstrates that human hepatocytes and HLM can be used with standard scaling approaches to predict the human in vivo clearance for FMO substrates. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  11. The Institution of a Standardized Investigation Protocol for Sudden Infant Death in the Eastern Metropole, Cape Town, South Africa,.

    Science.gov (United States)

    Dempers, Johan J; Coldrey, Jean; Burger, Elsie H; Thompson, Vonita; Wadee, Shabbir A; Odendaal, Hein J; Sens, Mary Ann; Randall, Brad B; Folkerth, Rebecca D; Kinney, Hannah C

    2016-11-01

    The rate for the sudden infant death syndrome (SIDS) in Cape Town, South Africa, is estimated to be among the highest in the world (3.41/1000 live births). In several of these areas, including those of extreme poverty, only sporadic, nonstandardized infant autopsy, and death scene investigation (DSI) occurred. In this report, we detail a feasibility project comprising 18 autopsied infants with sudden and unexpected death whose causes of death were adjudicated according to the 1991 NICHD definitions (SIDS, n = 7; known cause of death, n = 7; and unclassified, n = 4). We instituted a standardized autopsy and infant DSI through a collaborative effort of local forensic pathology officers and clinical providers. The high standard of forensic investigation met international standards, identified preventable disease, and allowed for incorporation of research. We conclude that an effective infant autopsy and DSI protocol can be established in areas with both high sudden unexpected infant death, and elsewhere. (SUID)/SIDS risk and infrastructure challenges. © 2016 American Academy of Forensic Sciences.

  12. In vivo performance of a matrix-based quantitative ultrasound imaging device dedicated to calcaneus investigation.

    Science.gov (United States)

    Gomez, M A; Defontaine, M; Giraudeau, B; Camus, E; Colin, L; Laugier, P; Patat, F

    2002-10-01

    We developed a prototype of an ultrasound (US) bone matrix densitometer, the BEAM scanner, in the context of a European Space Agency research program. This device, which is a contact imaging device, was designed to overcome the limitations of immersion devices in space. Broadband US attenuation (BUA) and speed of sound (SOS) parameters were calculated from the radiofrequency (RF) signal. The principle aim of this study was to evaluate in vivo performance in direct comparison with a currently available device (UBIS 3000, DMS, France). The short-term precision of the BEAM scanner for BUA was estimated at 2.8%, whereas it was 2.3% with UBIS 3000. The short-term precision for SOS was 0.3%, and this was the same as the coefficient of variation (CV) of the UBIS 3000. CVs of 3.4% and 0.6% for midterm precision were found for BUA and SOS, respectively, and UBIS 3000 scores were 3% and 0.4%, respectively. This preliminary study demonstrates the high performance of the BEAM scanner and its new concept offers a wide range of improvements and new applications.

  13. Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits.

    Science.gov (United States)

    Kivelio, A; Dekoninck, P; Perrini, M; Brubaker, C E; Messersmith, P B; Mazza, E; Deprest, J; Zimmermann, R; Ehrbar, M; Ochsenbein-Koelble, N

    2013-12-01

    Iatrogenic preterm prelabour rupture of fetal membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. The aim of this study was to evaluate the sealing capability and tissue interaction of mussel-mimetic tissue adhesive (mussel glue) in comparison to fibrin glue on punctured fetal membranes in vivo. A mid-gestational rabbit model was used for testing the materials. The fetal sacs of pregnant rabbits at day 23 were randomly assigned into experimental groups: unoperated (negative control), unclosed puncture (positive control), commercially available fibrin glue (FG) with decellularized amnion scaffold (DAM), mussel glue (MG) with DAM, or mussel glue alone. Evaluation was done at term (30 days' gestation) assessing fetal survival, fetal membrane integrity and histology of the membranes. Fetal survival was not significantly lower in any of the treatment groups compared to the negative control. All plugging materials could be found at the end of the pregnancy and no adverse effects on the fetus or the pregnant does could be observed. Sac integrity was higher in all treatment groups compared to the positive control group but significant only in the FG+DAM group. Cellular infiltration could be seen in fibrin glue and DAM in contrast to mussel glue which was only tightly adhering to the surrounding tissue. These cells were mostly of mesenchymal phenotype staining positive for vimentin. CD68 positive macrophages were found clustered around all the plugging materials, but their numbers were only significantly increased for the mussel glue alone group compared to negative controls. Mussel glues performance in sealing fetal membranes in the rabbit model was comparable to that of fibrin glue. Taking into account its other favorable properties, it is a noteworthy candidate for a clinically applicable fetal membrane sealant. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Experimental investigation on the mechanical behavior of polyurethane PICCs after long-term conservation in in vivo-like conditions.

    Science.gov (United States)

    Di Puccio, Francesca; Gallone, Giuseppe; Baù, Andrea; Calabrò, Emanuele M; Mainardi, Simona; Poli, Paolo; Scocca, Antonella

    2017-11-17

    In a previous paper, the authors investigated the mechanical behavior of several commercial polyurethane peripherally inserted central venous catheters (PICCs) in their 'brand new' condition. The present study represents a second step of the research activity and aims to investigate possible modifications of the PICC mechanical response, induced by long-term conservation in in vivo-like conditions, particularly when used to introduce oncologic drugs. Eight 5 Fr single-lumen catheters from as many different vendors, were examined. Several specimens were cut from each of them and kept in a bath at 37°C for 1, 2, 3 and 6 months. Two fluids were used to simulate in vivo-like conditions, i.e. ethanol and Ringer-lactate solutions, the first being chosen in order to reproduce a typical chemical environment of oncologic drugs. The test plan included swelling analyses, uniaxial tensile tests and dynamic mechanical thermal analysis (DMTA). All tested samples were chemically and mechanically stable in the studied conditions, as no significant weight variation was observed even after six months of immersion in ethanol solution. Uniaxial tensile tests confirmed such a response. For each PICC, very similar curves were obtained from samples tested after different immersion durations in the two fluid solutions, particularly for strains lower than 10%.

  15. PET imaging with copper-64 as a tool for real-time in vivo investigations of the necessity for crosslinking of polymeric micelles in nanomedicine

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann; Binderup, Tina; Ek, Pramod Kumar

    2017-01-01

    Polymeric micelles in nanomedicine are often crosslinked to prevent disintegration in vivo. This typically requires clinically problematic chemicals or laborious procedures. In addition, crosslinking may interfere with advanced release strategies. Despite this, it is often not investigated whether...

  16. Significance of different animal species in experimental models for in vivo investigations of hematopoiesis

    Directory of Open Access Journals (Sweden)

    Kovačević-Filipović Milica

    2004-01-01

    Full Text Available Numerous discoveries in medicine are results of experiments on different animal species. The most frequently used animals in hematopoiesis investigations are laboratory mice and rats, but so-called big animals, such as pigs, sheep, cats, dogs, and monkeys, evolution-wise closer to humans have a place in experimental hematology as well. The specific problematics of a certain animal specie can lead to fundamental knowledge on certain aspects of the process of hematopoiesis end the biology of stem cells in hematopoiesis. Furthermore, comparative investigations of certain phenomena in different species help in the recognition of the general rules in the living world. In the area f preclinicalinvesti- gations, animal models are an inevitable step in studies of transplantation biology of stem cells in hematopoiesis, as well as in studies of biologically active molecules which have an effect on the hematopoietic system. Knowledge acquired on animal models is applied in both human and veterinary medicine.

  17. Redundant systematic reviews on the same topic in surgery: a study protocol for a meta-epidemiological investigation.

    Science.gov (United States)

    Katsura, Morihiro; Kuriyama, Akira; Tada, Masafumi; Yamamoto, Kazumichi; Furukawa, Toshi A

    2017-08-21

    We are witnessing an explosive increase in redundant and overlapping publications of systematic reviews and meta-analyses (SRs/MAs) on the same topic, which often present conflicting results and interpretations, in the current medical literature. They represent wasted efforts on the part of investigators and peer reviewers and may confuse and possibly mislead clinicians and policymakers. Here, we present a protocol for a meta-epidemiological investigation to describe how often there are overlapping SRs/MAs on the same topic, to assess the quality of these multiple publications, and to investigate the causes of discrepant results between multiple SRs/MAs in the field of major surgery. We will use MEDLINE/PubMed to identify all SRs/MAs of randomised controlled trials (RCTs) published in 2015 regarding major surgical interventions. After identifying the 'benchmark' SRs/MAs published in 2015, a process of screening in MEDLINE will be carried out to identify the previous SRs/MAs of RCTs on the same topic that were published within 5 years of the 'benchmark' SRs/MAs. We will tabulate the number of previous SRs/MAs on the same topic of RCTs, and then describe their variations in numbers of RCTs included, sample sizes, effect size estimates and other characteristics. We will also assess the differences in quality of each SR/MA using A Measurement Tool to Assess Systematic Reviews (AMSTAR) score. Finally, we will investigate the potential reasons to explain the discrepant results between multiple SRs/MAs. No formal ethical approval and informed consent are required because this study will not collect primary individual data. The intended audiences of the findings include clinicians, healthcare researchers and policymakers. We will publish our findings as a scientific report in a peer-reviewed journal. In PROSPERO CRD42017059077, March 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial

  18. Investigation in vivo of Enterococcus faecalis in endodontic retreatment by phenotypic and genotypic methods

    Directory of Open Access Journals (Sweden)

    Marcos Sergio Endo

    2015-06-01

    Full Text Available This study aimed to investigate the prevalence of E. faecalis in root-filled canals using culture and molecular approaches. It was evaluated the antimicrobial susceptibility to different antibiotics and the virulence factors of E. faecalis isolates. Microbial samples were taken from thirty root-filled canals. Culture methods and 16S rDNA assay were used to identify E. faecalis. The antimicrobial susceptibility of E. faecalis was determined by MIC values using the E test. Cultivable strains of E. faecalis were investigated for virulence factors by PCR technique. E. faecalis were detected by culture (7/30, traditional PCR assay (13/30 and nested PCR (23/30. Both PCR were significantly more effective than culture in detecting  E. faecalis (p < 0.05. All tested E. faecalis were highly sensitive to amoxicillin. Some strains of E. faecalis were resistant to antibiotics such as rifampicin (4/12, erythromycin (3/12 and azythromycin (8/12. The genes efaA and ace were detected in all isolates. The other virulence genes were found in 91.6 (gelE, 83.3 (asa, 25 (esp and 16.6% (cylA. Strains of E. faecalis isolated from root-filled canals showed virulence factors related to adherence. They also showed resistance to some antibiotics commonly used in dentistry.

  19. In vivo investigations of neurotensin receptors in adipocytes, hepatocytes and enterocytes of rat.

    Science.gov (United States)

    Piątek, Jacek; Maćkowiak, Paweł; Krauss, Hanna; Nowak, Dorota; Bogdański, Paweł

    2011-01-01

    Atherosclerotic vascular disease is currently the biggest threat and the highest cause of death worldwide, approaching almost 60%.The development of atherosclerosis is affected by ecological factors associated with industry and pollution of the environment. Neurotensin (NT) is a peptide acting via 3 kinds of neurotensin receptors (NTR) localized in target tissues. In several studies, the presence of its receptors has been shown in chicken liver, and the influence of NT on the metabolism of this organ was confirmed (glycogenolysis stimulation through sympathetic nervous system, enterohepatic circulation of bile acids, metabolism of lipoproteins). Healthy male WISTAR rats weighing 300}30 grams, were used for the experiments. The animals were divided into 4 groups: 1) control group, to which 0.9% NaCl was administrated (i.p.); 2) the second group was given levocabastine 1mg/kg i.p.; 3) the third group received SR 48692 0.4 mg/; 4) the fourth group was given NT analog [D-Trp 11]-neurotensin 15 nM/kg. Plasmatic membranes of liver, small intestine and adipose tissue were prepared according to the method of Havrankova. Analysis of results obtained in the investigation of NT receptors was performed using the Scatchard method from LIGAND-Pc, v. 3.1 software. The investigation of antigenity of I125NT showed proper antigen-antibody reaction. No binding of the I125NT with plasmatic membranes of adipocytes or enterocytes was observed. Unspecific binding of I125NT with 10 μmol/L of free NT was observed in the plasmatic membranes of hepatocytes. The presence of NT receptors only in the membranes of hepatocytes may suggest their role in the regulation of lipid metabolism via receptor – ligand way.

  20. Development and validation of Triticum phytobiological method as an alternative procedure for investigating in vivo acute toxicity on mice

    Directory of Open Access Journals (Sweden)

    Emil Ştefănescu

    2017-10-01

    Full Text Available The goal of this study was to validate an alternative method for determining in vivo acute toxicity using vegetal material instead of laboratory animals, starting from the phytobiological method known also as the Triticum technique. We set out to demonstrate that vegetal cells have similar sensitivity to some toxic agents as animal cells, in which case a statistical correlation could be established. A series of new compounds synthesized by the Romanian National Institute for Chemical Pharmaceutical Research and Development as potential β3 adrenergic receptors agonists were tested for their acute toxicity using classic animal exposure models, before investigating possible anti-diabetic and anti-obesity effects. We then determined whether similar conclusions might be reached exposing vegetal material to the same agents. We successfully demonstrated that plants are affected in a very similar way as animals when exposed to some potentially toxic agents, providing new possibilities for ending unethical animal experiments.

  1. Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).

    Science.gov (United States)

    Ronchi, Silas Nascimento; Brasil, Girlandia Alexandre; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Scherer, Rodrigo; Costa, Helber B; Romão, Wanderson; Boëchat, Giovanna Assis Pereira; Lenz, Dominik; Fronza, Marcio; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

    2015-10-01

    The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays. The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis. The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril. Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting

  2. Use of a structured investigative protocol enhances young children's responses to free-recall prompts in the course of forensic interviews.

    Science.gov (United States)

    Sternberg, K J; Lamb, M E; Orbach, Y; Esplin, P W; Mitchell, S

    2001-10-01

    One hundred alleged victims of child sexual abuse (ages 4-12 years; M = 8.1 years) were interviewed by police investigators about their alleged experiences. Half of the children were interviewed using the National Institute of Child Health and Human Development's structured interview protocol, whereas the other children--matched with respect to their age, relationship with the alleged perpetrator, and seriousness of the alleged offenses--were interviewed using standard interview practices. Protocol-guided interviews elicited more information using open-ended prompts and less information using option-posing and suggestive questions than did standard interviews; there were no age differences in the amount of information provided in response to open-ended invitations. In 89% of the protocol interviews, children made their preliminary allegations in response to open-ended prompts, compared with 36% in the standard interviews.

  3. Investigating the clinical feasibility of an adapted early mobility readiness protocol for critical ill patients: A non-randomised experimental pilot trial.

    Science.gov (United States)

    Conradie, Elmarie; Fourie, Catharina E; Hanekom, Susan D

    2017-10-01

    Uncertainty exists whether a therapeutic early mobility position will affect the outcome of a critically ill patient. To evaluate the feasibility of an existing protocol to identify patients who would tolerate this position. A non-randomised experimental pilot trail was performed. Twice weekly, all patients nursed in surgical and respiratory units were screened with the protocol. Haemodynamic parameters, mean arterial pressure and central venous oxygen saturation of included patients were tested in the baseline position followed by the testing position at 0, 3 and 10minutes. We screened 138 patients. Eleven patients passed the protocol, male/female (9/2) with a median (range) age of 47 (20-67) years. Placement from the 10minutes baseline position to the 0min testing position resulted in a mean difference of the mean arterial pressure of 2.03 (95% Confidence interval -1.12 to 5.18), and the mean difference of central venous oxygen saturation was 0.79 (95% Confidence interval -3.15 to 4.74). One adverse event was noted. The protocol provides healthcare professionals with an interim tool to identify patients who would tolerate a therapeutic upright position. While the results question the clinical feasibility of protocol. The effect of incorporating a therapeutic early mobility position into standard nursing care, on patient outcome can now be investigated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Mechanisms of in vivo muscle fatigue in humans: investigating age‐related fatigue resistance with a computational model

    Science.gov (United States)

    Callahan, Damien M.; Umberger, Brian R.

    2016-01-01

    Key points Muscle fatigue can be defined as the transient decrease in maximal force that occurs in response to muscle use. Fatigue develops because of a complex set of changes within the neuromuscular system that are difficult to evaluate simultaneously in humans.The skeletal muscle of older adults fatigues less than that of young adults during static contractions. The potential sources of this difference are multiple and intertwined.To evaluate the individual mechanisms of fatigue, we developed an integrative computational model based on neural, biochemical, morphological and physiological properties of human skeletal muscle.Our results indicate first that the model provides accurate predictions of fatigue and second that the age‐related resistance to fatigue is due largely to a lower reliance on glycolytic metabolism during contraction.This model should prove useful for generating hypotheses for future experimental studies into the mechanisms of muscle fatigue. Abstract During repeated or sustained muscle activation, force‐generating capacity becomes limited in a process referred to as fatigue. Multiple factors, including motor unit activation patterns, muscle fibre contractile properties and bioenergetic function, can impact force‐generating capacity and thus the potential to resist fatigue. Given that neuromuscular fatigue depends on interrelated factors, quantifying their independent effects on force‐generating capacity is not possible in vivo. Computational models can provide insight into complex systems in which multiple inputs determine discrete outputs. However, few computational models to date have investigated neuromuscular fatigue by incorporating the multiple levels of neuromuscular function known to impact human in vivo function. To address this limitation, we present a computational model that predicts neural activation, biomechanical forces, intracellular metabolic perturbations and, ultimately, fatigue during repeated isometric contractions

  5. In vivo and in vitro investigations of retinal fluorophores in age-related macular degeneration by fluorescence lifetime imaging

    Science.gov (United States)

    Hammer, M.; Quick, S.; Klemm, M.; Schenke, S.; Mata, N.; Eitner, A.; Schweitzer, D.

    2009-02-01

    Ocular fundus autofluorescence imaging has been introduced into clinical diagnostics recently for the observation of the age pigment lipofuscin, a precursor of age-related macular degeneration (AMD). However, a deeper understanding of the generation of single compounds contributing to the lipofuscin as well as of the role of other fluorophores such as FAD, glycated proteins, and collagen needs their discrimination by fluorescence lifetime imaging (FLIM). FLIM at the ocular fundus is performed using a scanning laser ophthalmoscope equipped with a picosecond laser source (448nm or 468nm respectively, 100ps, 80 MHz repetition rate) and dual wavelength (490-560nm and 560-7600nm) time-correlated single photon counting. A three-exponential fit of the fluorescence decay revealed associations of decay times to anatomical structures. Disease-related features are identified from alterations in decay times and-amplitudes. The in-vivo investigations in patients were paralleled by experiments in an organ culture of the porcine ocular fundus. Photo-oxidative stress was induced by exposure to blue light (467nm, 0.41 mW/mm2). Subsequent analysis (fluorescence microscopy, HPLC, LC-MS) indicated the accumulation of the pyridinium bis-retinoid A2E and its oxidation products as well as oxidized phospholipids. These compounds contribute to the tissue auto-fluorescence and may play a key role in the pathogenesis of AMD. Thus, FLIM observation at the ocular fundus in vivo enhances our knowledge on the etiology of AMD and may become a diagnostic tool.

  6. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

    Directory of Open Access Journals (Sweden)

    Al Asmari AK

    2016-10-01

    Full Text Available Abdulrahman K Al Asmari, Abdul Quaiyoom Khan Research Centre, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Abstract: Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo antitumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone. Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 µg, 35 µg, and 52.5 µg per animal were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules. Keywords: Leiurus quinquestriatus, skin cancer, apoptosis, immunosuppression

  7. TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

    Science.gov (United States)

    This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

  8. Pre-analytical factors in clinical proteomics investigations: impact of ex vivo protein modifications for multiple sclerosis biomarker discovery.

    Science.gov (United States)

    Pieragostino, Damiana; Petrucci, Francesca; Del Boccio, Piero; Mantini, Dante; Lugaresi, Alessandra; Tiberio, Sara; Onofrj, Marco; Gambi, Domenico; Sacchetta, Paolo; Di Ilio, Carmine; Federici, Giorgio; Urbani, Andrea

    2010-01-03

    Serum proteome investigations have raised an incredible interest in the research of novel molecular biomarker, nevertheless few of the proposed evidences have been translated to the clinical practice. One of the limiting factors has been the lack of generally accepted guidelines for clinical proteomics studies and the lack of a robust analytical and pre-analytical ground for the proposed classification models. Pre-analytical issues may results in a deep impact for biomarker discovery campaign. In this study we present a systematic evaluation of sample storage and sampling conditions for clinical proteomics investigations. We have developed and validated a linear MALDI-TOF-MS protein profiling method to explore the low protein molecular weight region (5-20 kDa) of serum samples. Data normalization and processing was performed using optimise peak detection routine (LIMPIC) able to describe each group under investigation. Data were acquired either from healthy volunteers and from multiple sclerosis patients in order to highlight ex vivo protein profile alteration related to different physio-pathological conditions. Our data showed critical conditions for serum protein profiles depending on storage times and temperatures: 23 degrees C, 4 degrees C, -20 degrees C and -80 degrees C. We demonstrated that upon a -20 degrees C short term storage, characteristic degradation profiles are associated with different clinical groups. Protein signals were further identified after preparative HPLC separation by peptide sequencing on a nanoLC-Q-TOF TANDEM mass spectrometer. Apolipoprotein A-IV and complement C3 protein fragments, transthyretin and the oxidized isoforms in different apolipoprotein species represent the major molecular features of such a degradation pattern. (c) 2009 Elsevier B.V. All rights reserved.

  9. Application of two segmentation protocols during the processing of virtual images in rapid prototyping: ex vivo study with human dry mandibles.

    Science.gov (United States)

    Ferraz, Eduardo Gomes; Andrade, Lucio Costa Safira; dos Santos, Aline Rode; Torregrossa, Vinicius Rabelo; Rubira-Bullen, Izabel Regina Fischer; Sarmento, Viviane Almeida

    2013-12-01

    The aim of this study was to evaluate the accuracy of virtual three-dimensional (3D) reconstructions of human dry mandibles, produced from two segmentation protocols ("outline only" and "all-boundary lines"). Twenty virtual three-dimensional (3D) images were built from computed tomography exam (CT) of 10 dry mandibles, in which linear measurements between anatomical landmarks were obtained and compared to an error probability of 5 %. The results showed no statistically significant difference among the dry mandibles and the virtual 3D reconstructions produced from segmentation protocols tested (p = 0,24). During the designing of a virtual 3D reconstruction, both "outline only" and "all-boundary lines" segmentation protocols can be used. Virtual processing of CT images is the most complex stage during the manufacture of the biomodel. Establishing a better protocol during this phase allows the construction of a biomodel with characteristics that are closer to the original anatomical structures. This is essential to ensure a correct preoperative planning and a suitable treatment.

  10. Quality assessment in in vivo NMR spectroscopy: V. Multicentre evaluation of prototype test objects and protocols for performance assessment in small bore MRS equipment

    DEFF Research Database (Denmark)

    Howe, F.A.; Canese, R; Podo, F

    1995-01-01

    This paper reports the results of multicentre studies aimed at designing, constructing, and evaluating prototype test objects for performance assessment in small-bore MRS systems, by utilizing the test protocols already proposed by the EEC COMAC-BME Concerted Action for clinical MRS equipment...

  11. Delayed voluntary exercise does not enhance cognitive performance after hippocampal injury: an investigation of differentially distributed exercise protocols

    OpenAIRE

    Wogensen, Elise; Gram, Marie Gajhede; Sommer, Jens Bak; Vilsen, Christina Rytter; Mogensen, Jesper; Mal?, Hana

    2016-01-01

    Voluntary exercise has previously been shown to enhance cognitive recovery after acquired brain injury (ABI). The present study evaluated effects of two differentially distributed protocols of delayed, voluntary exercise on cognitive recovery using an allocentric place learning task in an 8-arm radial maze. Fifty-four Wistar rats were subjected to either bilateral transection of the fimbria-fornix (FF) or to sham surgery. Twenty-one days postinjury, the animals started exercising in running w...

  12. Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf extract in the streptozotocin-induced diabetic rat.

    Science.gov (United States)

    Magielse, Joanna; Verlaet, Annelies; Breynaert, Annelies; Keenoy, Begoña Manuel Y; Apers, Sandra; Pieters, Luc; Hermans, Nina

    2014-01-01

    The in vivo antioxidant activity of a quantified leaf extract of Cynara scolymus (artichoke) was studied. The aqueous artichoke leaf extract (ALE), containing 1.5% caffeoylquinic acid with chlorogenic acid being most abundant (0.30%), and luteolin-7-O-glucoside as major flavonoid (0.15%), was investigated by evaluating the effect on different oxidative stress biomarkers, after 3 wk oral supplementation in the streptozotocin-induced diabetic rat model. Apart from two test groups (0.2 g ALE/kg BW/day and 1 g ALE/kg BW/day, where BW is body weight), a healthy control group, untreated oxidative stress group, and vitamin E treated group (positive control) were included. A 0.2 g/kg BW/day of ALE decreased oxidative stress: malondialdehyde and 8-hydroxydeoxyguanosine levels significantly diminished, whereas erythrocyte glutathione levels significantly increased. A 1.0 g/kg BW/day ALE did not show higher antioxidant activity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Hemocyte responses of Dreissena polymorpha following a short-term in vivo exposure to titanium dioxide nanoparticles: Preliminary investigations

    Energy Technology Data Exchange (ETDEWEB)

    Couleau, Nicolas; Techer, Didier [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Pagnout, Christophe [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); International Consortium for the Environmental Implications of Nanotechnology, iCEINT, http://www.i-ceint.org (France); Jomini, Stephane [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); Foucaud, Laurent; Laval-Gilly, Philippe; Falla, Jairo [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Bennasroune, Amar, E-mail: amar.bennasroune@univ-metz.fr [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France)

    2012-11-01

    The widespread use of titanium-based nanoparticles and their environmental release may pose a significant risk to aquatic organisms within freshwater ecosystems. Suspension-feeder invertebrates like bivalve molluscs represent a unique target group for nanoparticle toxicology. The aim of this work was to investigate the short-term responses of Dreissena polymorpha hemocytes after in vivo exposure to titanium dioxide nanoparticles (TiO{sub 2} NP). For this purpose, freshwater mussels were exposed to P25 TiO{sub 2} NP at the concentrations of 0.1, 1, 5 and 25 mg/L during 24 h. Viability, phagocytosis activity and mitogen activated protein kinase (MAPK) phosphorylation level of ERK 1/2 and p38 in hemocytes extracted from exposed mussels were compared to those from control specimens. Results demonstrated an inhibition of the phagocytosis activity after exposure to TiO{sub 2} NP at 0.1 and 1 mg/L. Similar trends, albeit less pronounced, were reported for higher concentrations of NP. Transmission electron microscopy showed for the first time the internalization of TiO{sub 2} NP into Dreissena polymorpha hemocytes. Besides, exposure to NP increased the ERK 1/2 phosphorylation levels in all treatments. Concerning the phosphorylation level of p38, only exposures to 5 and 25 mg/L of NP induced significant p38 activation in comparison to that of the control. Finally, these short-term effects observed at environmentally relevant concentrations highlighted the need for further studies concerning ecotoxicological evaluation of nanoparticle release into an aquatic environment. -- Highlights: Black-Right-Pointing-Pointer Phagocytosis inhibition at TiO{sub 2} NP exposure concentrations of 0.1 and 1 mg/L. Black-Right-Pointing-Pointer Internalization of TiO{sub 2} NP in freshwater mussel hemocytes. Black-Right-Pointing-Pointer Increased phosphorylation level of p38 and ERK 1/2 after in vivo exposure to TiO{sub 2} NP.

  14. Antioxidant activity of omega-3 derivatives and their delivery via nanocages and nanocones: DFT and experimental in vivo investigation.

    Science.gov (United States)

    Najafi, Houshang; Changizi-Ashtiyani, Saeed; Najafi, Meysam

    2017-10-28

    The antioxidant properties of omega-3 were investigated via experimental in vivo and theoretical methods. For experimental evaluation, oxidative stress was induced by 30 min bilateral renal ischemia and 24 h of reperfusion in male Sprague Dawley rats. The oxidative stress was evaluated through measuring malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) levels in renal tissue. In theoretical methods, the reaction enthalpies of antioxidant mechanisms of omega-3 were calculated and the effects of NHMe, OMe, OH, Cl, and Me substituents on its antioxidant activity were investigated. Moreover, the omega-3 delivery potential by carbon and boron nitride nanocages and naocones were evaluated. The experimental results showed that omega-3 administration decreases MDA and increases FRAP levels after their changes by ischemia/reperfusion. Theoretical results indicated that NHMe and OMe substituents can significantly improve the antioxidant activity of omega-3. Also, boron nitride nanocone (BNNC) has higher |∆Ead| values, so it has higher potential for omega-3 delivery. Taken together, the new findings presented here indicate that omega-3 has anti-oxidative properties and NHMe and OMe substituents can improve its antioxidant activity. Moreover, adsorption of omega-3 on the surface of the studied nanostructures was exothermic, and BNNC with higher |∆Ead| values has higher potential for omega-3 delivery. Graphical abstract The interaction and adsorption of BNNC with omega-3 is exothermic and experimentally possible from the energetic viewpoint, so the BNNC with higher |∆Ead| and |∆Gad| values has higher potential for omega-3 delivery.

  15. A proboscis extension response protocol for investigating behavioral plasticity in insects: application to basic, biomedical, and agricultural research.

    Science.gov (United States)

    Smith, Brian H; Burden, Christina M

    2014-09-08

    Insects modify their responses to stimuli through experience of associating those stimuli with events important for survival (e.g., food, mates, threats). There are several behavioral mechanisms through which an insect learns salient associations and relates them to these events. It is important to understand this behavioral plasticity for programs aimed toward assisting insects that are beneficial for agriculture. This understanding can also be used for discovering solutions to biomedical and agricultural problems created by insects that act as disease vectors and pests. The Proboscis Extension Response (PER) conditioning protocol was developed for honey bees (Apis mellifera) over 50 years ago to study how they perceive and learn about floral odors, which signal the nectar and pollen resources a colony needs for survival. The PER procedure provides a robust and easy-to-employ framework for studying several different ecologically relevant mechanisms of behavioral plasticity. It is easily adaptable for use with several other insect species and other behavioral reflexes. These protocols can be readily employed in conjunction with various means for monitoring neural activity in the CNS via electrophysiology or bioimaging, or for manipulating targeted neuromodulatory pathways. It is a robust assay for rapidly detecting sub-lethal effects on behavior caused by environmental stressors, toxins or pesticides. We show how the PER protocol is straightforward to implement using two procedures. One is suitable as a laboratory exercise for students or for quick assays of the effect of an experimental treatment. The other provides more thorough control of variables, which is important for studies of behavioral conditioning. We show how several measures for the behavioral response ranging from binary yes/no to more continuous variable like latency and duration of proboscis extension can be used to test hypotheses. And, we discuss some pitfalls that researchers commonly encounter

  16. Ex vivo evaluation of four final irrigation protocols on the removal of hard-tissue debris from the mesial root canal system of mandibular first molars.

    Science.gov (United States)

    Leoni, G B; Versiani, M A; Silva-Sousa, Y T; Bruniera, J F B; Pécora, J D; Sousa-Neto, M D

    2017-04-01

    To evaluate the efficacy of four final irrigation protocols on the reduction of hard-tissue debris accumulated within the mesial root canal system of mandibular first molars using micro-CT analysis. Forty mesial roots of mandibular molars with a single and continuous isthmus connecting the mesiobuccal and mesiolingual canals (Vertucci's Type I configuration) were selected and scanned at a resolution of 8.6 μm. Canals were enlarged sequentially using WaveOne Small and Primary instruments activated in reciprocating motion without intracanal irrigation to allow debris to accumulate within the mesial root canal system. Then, specimens were anatomically matched and distributed into four groups (n = 10), according to the final irrigation protocol: apical positive pressure (APP), passive ultrasonic irrigation (PUI), Self-adjusting File (SAF) and XP-endo Finisher (XPF). The final irrigation procedures were performed over 2 min using a total of 5.5 mL of 2.5% NaOCl per canal. Reconstructed data sets were coregistered, and the mean percentage reduction of accumulated hard-tissue debris after the final irrigation procedures was compared statistically between groups using the anovapost hoc Tukey test with a significance level set at 5%. Reduction of accumulated hard-tissue debris was observed in all groups after the final irrigation protocol. Overall, PUI and XPF groups had higher mean percentage reductions of accumulated hard-tissue debris (94.1% and 89.7%, respectively) than APP and SAF groups (45.7% and 41.3%, respectively) (P  0.05) or APP and SAF groups (P > 0.05). The PUI technique and XP-endo Finisher instrument were associated with significantly lower levels of AHTD compared with conventional irrigation and the modified SAF system protocol in mesial root canals of mandibular molars. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  17. Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence

    DEFF Research Database (Denmark)

    Schallig, Henk D. F. H.; Tinto, Halidou; Sawa, Patrick

    2017-01-01

    susceptibility to ACT in Africa have now been well documented. Strategies that retain current ACT as efficacious treatments are urgently needed. Methods We present an open-label, randomised three-arm clinical trial protocol in three African settings representative of varying malaria epidemiology to investigate......-inferior safety compared with standard single-course ACT given to 540 children. The primary endpoint is PCR-corrected clinical and parasitological response at day 42 or day 63 of follow-up. Persistence of PCR-detectable parasitaemia at day 3 is analysed as a key covariate. Secondary endpoints include...... gametocytaemia, occurrence of treatment-related adverse events in the double-ACT versus single-ACT arms, carriage of molecular markers of drug resistance, drug kinetics and patient adherence to treatment. Discussion This protocol addresses efficacy and safety of sequential ACT regimens in P. falciparum malaria...

  18. Unexplained developmental delay/learning disability: guidelines for best practice protocol for first line assessment and genetic/metabolic/radiological investigations.

    Science.gov (United States)

    O'Byrne, J J; Lynch, S A; Treacy, E P; King, M D; Betts, D R; Mayne, P D; Sharif, F

    2016-02-01

    Investigation of patients, particularly children, with unexplained global developmental delay (GDD)/learning disability (LD) has been challenging due to a lack of clear guidance from specialised centres. Limited knowledge of rare diseases and a poor understanding of the purpose or limitations of appropriate investigations have been some of the principal reasons for this difficulty. A guideline development group was formed to recommend on appropriate, first line metabolic, genetic and radiological investigations for children and adults with unexplained GDD/ID. A comprehensive literature search was conducted, evaluated and reviewed by the guideline committee and a best practice protocol for first line assessment and genetic, metabolic and radiological investigations was decided upon after considering diagnostic yield, practicality, treatability and costs. It is hoped that these recommendations will become national guidelines for the first line metabolic, genetic and radiological investigation of patients presenting with unexplained GDD/ID.

  19. The German AugUR study: study protocol of a prospective study to investigate chronic diseases in the elderly.

    Science.gov (United States)

    Stark, Klaus; Olden, Matthias; Brandl, Caroline; Dietl, Alexander; Zimmermann, Martina E; Schelter, Sabine C; Loss, Julika; Leitzmann, Michael F; Böger, Carsten A; Luchner, Andreas; Kronenberg, Florian; Helbig, Horst; Weber, Bernhard H F; Heid, Iris M

    2015-10-21

    The majority of patients suffering from chronic health disabilities is beyond 70 years of age. Typical late-onset chronic diseases include those affecting the heart, the kidney, cancer, and conditions of the eye such as age-related macular degeneration. These diseases disable patients for many years and largely compromise autonomy in daily life. Due to challenges in recruiting the elderly, the collection of population-based epidemiological data as a prerequisite to understand associated risk factors and mechanisms is commonly done in the general population within an age-range of 20 to 70 years. We establish the German AugUR study (Age-related diseases: understanding genetic and non-genetic influences - a study at the University of Regensburg), a prospective study in the mobile elderly general population in and around Regensburg in eastern Bavaria. In the long term, we aim to recruit 3,000 persons of Caucasian ethnicity with at least 70 years of age via residents' registration offices and conduct 3-year follow-ups. The study protocol includes a standardized interview regarding social and life-style factors, medication history, quality-of-life, and existing diagnoses of common diseases. The participants undergo medical examinations for ophthalmological, cardiovascular or diabetes-related conditions, and general measurements of body shape and fitness. The program is particularly tailored for the elderly. Biobanking of whole blood, serum, plasma, and urine is conducted and standard laboratory measurements are performed in fresh samples. AugUR is specifically designed as a research platform to host studies of late onset diseases. Consequently, this platform will help (1) to unravel the genetic and non-genetic etiology of disease development and progression, (2) to serve as control group of elderly individuals for comparisons with various patient groups, (3) to derive prevalence and incidence data on chronic diseases, and (4) to provide clinical reference parameters

  20. Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-(13)C2]pyruvate in vivo.

    Science.gov (United States)

    Chen, Albert P; Hurd, Ralph E; Schroeder, Marie A; Lau, Angus Z; Gu, Yi-ping; Lam, Wilfred W; Barry, Jennifer; Tropp, James; Cunningham, Charles H

    2012-02-01

    (13)C MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of prepolarized [1-(13)C]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non-invasively. However, to allow investigation of Krebs cycle metabolism, the (13)C label must be placed on the C2 position of pyruvate. Thus, the utilization of either C1 or C2 labeled prepolarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the prepolarized pyruvate molecules were labeled at both C1 and C2 positions, then it would be possible to observe the downstream metabolites that were the results of both PDH flux ((13)CO(2) and H(13)CO(3)(-)) and Krebs cycle flux ([5-(13)C]glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the (13)CO(2) resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve (13)CO(2) detection, the feasibility of using dual-labeled hyperpolarized [1,2-(13)C(2)]pyruvate as a substrate for dynamic cardiac metabolic MRS studies to allow simultaneous investigation of PDH flux, Krebs cycle flux and pH, was demonstrated in vivo. Copyright © 2011 John Wiley & Sons, Ltd.

  1. Persistent Luminescence Nanophosphor Involved Near-Infrared Optical Bioimaging for Investigation of Foodborne Probiotics Biodistribution in Vivo: A Proof-of-Concept Study.

    Science.gov (United States)

    Liu, Yaoyao; Liu, Jing-Min; Zhang, Dongdong; Ge, Kun; Wang, Peihua; Liu, Huilin; Fang, Guozhen; Wang, Shuo

    2017-09-20

    Probiotics has attracted great attention in food nutrition and safety research field, but thus far there are limited analytical techniques for visualized and real-time monitoring of the probiotics when they are ingested in vivo. Herein, the optical bioimaging technique has been introduced for investigation of foodborne probiotics biodistribution in vivo, employing the near-infrared (NIR) emitting persistent luminescence nanophosphors (PLNPs) of Cr 3+ -doped zinc gallogermanate (ZGGO) as the contrast nanoprobes. The ultrabrightness, super long afterglow, polydispersed size, low toxicity, and excellent photostability and biocompatibility of PLNPs were demonstrated to be qualified as a tracer for labeling probiotics via antibody (anti-Gram positive bacteria LTA antibody) recognition as well as contrast agent for long-term bioimaging the probiotics. In vivo optical bioimaging assay showed that the LTA antibody functionalized ZGGO nanoprobes that could be efficiently tagged to the probiobics were successfully applied for real-time monitoring and nondamaged probing of the biodistribution of probiotics inside the living body after oral administration. This work presents a proof-of-concept that exploited the bioimaging methodology for real-time and nondamaged researching the foodborne probiotics behaviors in vivo, which would open up a novel way of food safety detection and nutrition investigation.

  2. An in Vivo Investigation of Brain Inflammation in Gulf War Illness with Integrated PET/MR Imaging

    Science.gov (United States)

    2015-10-01

    previously  pending)     R01  AT007550  (PI:  Harris/Napadow)    Neuroimaging  Approaches  to  Deconstructing   Acupuncture  for...Kreisl WC, Fujita M, Dustin I, Khan O, Appel S, et al. Increased in vivo expression of an inflammatory marker in temporal lobe epilepsy . J Nuclear Med

  3. Mimicking titration experiments with MD simulations: A protocol for the investigation of pH-dependent effects on proteins

    Science.gov (United States)

    Socher, Eileen; Sticht, Heinrich

    2016-03-01

    Protein structure and function are highly dependent on the environmental pH. However, the temporal or spatial resolution of experimental approaches hampers direct observation of pH-induced conformational changes at the atomic level. Molecular dynamics (MD) simulation strategies (e.g. constant pH MD) have been developed to bridge this gap. However, one frequent problem is the sampling of unrealistic conformations, which may also lead to poor pKa predictions. To address this problem, we have developed and benchmarked the pH-titration MD (pHtMD) approach, which is inspired by wet-lab titration experiments. We give several examples how the pHtMD protocol can be applied for pKa calculation including peptide systems, Staphylococcus nuclease (SNase), and the chaperone HdeA. For HdeA, pHtMD is also capable of monitoring pH-dependent dimer dissociation in accordance with experiments. We conclude that pHtMD represents a versatile tool for pKa value calculation and simulation of pH-dependent effects in proteins.

  4. Q-ball imaging models: comparison between high and low angular resolution diffusion-weighted MRI protocols for investigation of brain white matter integrity

    Energy Technology Data Exchange (ETDEWEB)

    Caiazzo, Giuseppina; Trojsi, Francesca; Cirillo, Mario; Tedeschi, Gioacchino [MRI Research Center SUN-FISM-Neurological Institute for Diagnosis and Care ' ' Hermitage Capodimonte' ' , Naples (Italy); Second University of Naples, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Naples (Italy); Esposito, Fabrizio [University of Salerno, Department of Medicine and Surgery, Baronissi (Salerno) (Italy); Maastricht University, Department of Cognitive Neuroscience, Maastricht (Netherlands)

    2016-02-15

    Q-ball imaging (QBI) is one of the typical data models for quantifying white matter (WM) anisotropy in diffusion-weighted MRI (DwMRI) studies. Brain and spinal investigation by high angular resolution DwMRI (high angular resolution imaging (HARDI)) protocols exhibits higher angular resolution in diffusion imaging compared to low angular resolution models, although with longer acquisition times. We aimed to assess the difference between QBI-derived anisotropy values from high and low angular resolution DwMRI protocols and their potential advantages or shortcomings in neuroradiology. Brain DwMRI data sets were acquired in seven healthy volunteers using both HARDI (b = 3000 s/mm{sup 2}, 54 gradient directions) and low angular resolution (b = 1000 s/mm{sup 2}, 32 gradient directions) acquisition schemes. For both sequences, tract of interest tractography and generalized fractional anisotropy (GFA) measures were extracted by using QBI model and were compared between the two data sets. QBI tractography and voxel-wise analyses showed that some WM tracts, such as corpus callosum, inferior longitudinal, and uncinate fasciculi, were reconstructed as one-dominant-direction fiber bundles with both acquisition schemes. In these WM tracts, mean percent different difference in GFA between the two data sets was less than 5 %. Contrariwise, multidirectional fiber bundles, such as corticospinal tract and superior longitudinal fasciculus, were more accurately depicted by HARDI acquisition scheme. Our results suggest that the design of optimal DwMRI acquisition protocols for clinical investigation of WM anisotropy by QBI models should consider the specific brain target regions to be explored, inducing researchers to a trade-off choice between angular resolution and acquisition time. (orig.)

  5. Developing a Comparative Docking Protocol for the Prediction of Peptide Selectivity Profiles: Investigation of Potassium Channel Toxins

    Directory of Open Access Journals (Sweden)

    Serdar Kuyucak

    2012-02-01

    Full Text Available During the development of selective peptides against highly homologous targets, a reliable tool is sought that can predict information on both mechanisms of binding and relative affinities. These tools must first be tested on known profiles before application on novel therapeutic candidates. We therefore present a comparative docking protocol in HADDOCK using critical motifs, and use it to “predict” the various selectivity profiles of several major αKTX scorpion toxin families versus Kv1.1, Kv1.2 and Kv1.3. By correlating results across toxins of similar profiles, a comprehensive set of functional residues can be identified. Reasonable models of channel-toxin interactions can be then drawn that are consistent with known affinity and mutagenesis. Without biological information on the interaction, HADDOCK reproduces mechanisms underlying the universal binding of αKTX-2 toxins, and Kv1.3 selectivity of αKTX-3 toxins. The addition of constraints encouraging the critical lysine insertion confirms these findings, and gives analogous explanations for other families, including models of partial pore-block in αKTX-6. While qualitatively informative, the HADDOCK scoring function is not yet sufficient for accurate affinity-ranking. False minima in low-affinity complexes often resemble true binding in high-affinity complexes, despite steric/conformational penalties apparent from visual inspection. This contamination significantly complicates energetic analysis, although it is usually possible to obtain correct ranking via careful interpretation of binding-well characteristics and elimination of false positives. Aside from adaptations to the broader potassium channel family, we suggest that this strategy of comparative docking can be extended to other channels of interest with known structure, especially in cases where a critical motif exists to improve docking effectiveness.

  6. Study protocol: a randomised controlled trial investigating the effect of a healthy lifestyle intervention for people with severe mental disorders

    Directory of Open Access Journals (Sweden)

    Castle David

    2011-01-01

    Full Text Available Abstract Background The largest single cause of death among people with severe mental disorders is cardiovascular disease (CVD. The majority of people with schizophrenia and bipolar disorder smoke and many are also overweight, considerably increasing their risk of CVD. Treatment for smoking and other health risk behaviours is often not prioritized among people with severe mental disorders. This protocol describes a study in which we will assess the effectiveness of a healthy lifestyle intervention on smoking and CVD risk and associated health behaviours among people with severe mental disorders. Methods/Design 250 smokers with a severe mental disorder will be recruited. After completion of a baseline assessment and an initial face-to-face intervention session, participants will be randomly assigned to either a multi-component intervention for smoking cessation and CVD risk reduction or a telephone-based minimal intervention focusing on smoking cessation. Randomisation will be stratified by site (Newcastle, Sydney, Melbourne, Australia, Body Mass Index (BMI category (normal, overweight, obese and type of antipsychotic medication (typical, atypical. Participants will receive 8 weekly, 3 fortnightly and 6 monthly sessions delivered face to face (typically 1 hour or by telephone (typically 10 minutes. Assessments will be conducted by research staff blind to treatment allocation at baseline, 15 weeks, and 12-, 18-, 24-, 30- and 36-months. Discussion This study will provide comprehensive data on the effect of a healthy lifestyle intervention on smoking and CVD risk among people with severe mental disorders. If shown to be effective, this intervention can be disseminated to treating clinicians using the treatment manuals. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR identifier: ACTRN12609001039279

  7. Investigation of bacterial and archaeal communities: novel protocols using modern sequencing by Illumina MiSeq and traditional DGGE-cloning.

    Science.gov (United States)

    Kraková, Lucia; Šoltys, Katarína; Budiš, Jaroslav; Grivalský, Tomáš; Ďuriš, František; Pangallo, Domenico; Szemes, Tomáš

    2016-09-01

    Different protocols based on Illumina high-throughput DNA sequencing and denaturing gradient gel electrophoresis (DGGE)-cloning were developed and applied for investigating hot spring related samples. The study was focused on three target genes: archaeal and bacterial 16S rRNA and mcrA of methanogenic microflora. Shorter read lengths of the currently most popular technology of sequencing by Illumina do not allow analysis of the complete 16S rRNA region, or of longer gene fragments, as was the case of Sanger sequencing. Here, we demonstrate that there is no need for special indexed or tailed primer sets dedicated to short variable regions of 16S rRNA since the presented approach allows the analysis of complete bacterial 16S rRNA amplicons (V1-V9) and longer archaeal 16S rRNA and mcrA sequences. Sample augmented with transposon is represented by a set of approximately 300 bp long fragments that can be easily sequenced by Illumina MiSeq. Furthermore, a low proportion of chimeric sequences was observed. DGGE-cloning based strategies were performed combining semi-nested PCR, DGGE and clone library construction. Comparing both investigation methods, a certain degree of complementarity was observed confirming that the DGGE-cloning approach is not obsolete. Novel protocols were created for several types of laboratories, utilizing the traditional DGGE technique or using the most modern Illumina sequencing.

  8. Impacts of Humanized Mouse Models on the Investigation of HIV-1 Infection: Illuminating the Roles of Viral Accessory Proteins in Vivo

    Directory of Open Access Journals (Sweden)

    Eri Yamada

    2015-03-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 encodes four accessory genes: vif, vpu, vpr, and nef. Recent investigations using in vitro cell culture systems have shed light on the roles of these HIV-1 accessory proteins, Vif, Vpr, Vpu, and Nef, in counteracting, modulating, and evading various cellular factors that are responsible for anti-HIV-1 intrinsic immunity. However, since humans are the exclusive target for HIV-1 infection, conventional animal models are incapable of mimicking the dynamics of HIV-1 infection in vivo. Moreover, the effects of HIV-1 accessory proteins on viral infection in vivo remain unclear. To elucidate the roles of HIV-1 accessory proteins in the dynamics of viral infection in vivo, humanized mouse models, in which the mice are xenotransplanted with human hematopoietic stem cells, has been utilized. This review describes the current knowledge of the roles of HIV-1 accessory proteins in viral infection, replication, and pathogenicity in vivo, which are revealed by the studies using humanized mouse models.

  9. Ex vivo

    Science.gov (United States)

    Matsuda, Kant M; Lopes-Calcas, Ana; Honke, Michael L; O'Brien-Moran, Zoe; Buist, Richard; West, Michael; Martin, Melanie

    2017-07-01

    To advance magnetic resonance imaging (MRI) technologies further for in vivo tissue characterization with histopathologic validation, we investigated the feasibility of ex vivo tissue imaging of a surgically removed human brain tumor as a comprehensive approach for radiology-pathology correlation in histoanatomically identical fashion in a rare case of pigmented ganglioglioma with complex paramagnetic properties. Pieces of surgically removed ganglioglioma, containing melanin and hemosiderin pigments, were imaged with a small bore 7-T MRI scanner to obtain T1-, T2-, and T2*-weighted image and diffusion tensor imaging (DTI). Corresponding histopathological slides were prepared for routine hematoxylin and eosin stain and special stains for melanin and iron/hemosiderin to correlate with MRI signal characteristics. Furthermore, mean diffusivity (MD) maps were generated from DTI data and correlated with cellularity using image analysis. While the presence of melanin was difficult to interpret in in vivo MRI with certainty due to concomitant hemosiderin pigments and calcium depositions, ex vivo tissue imaging clearly demonstrated pieces of tissue exhibiting the characteristic MR signal pattern for melanin with pathologic confirmation in a histoanatomically identical location. There was also concordant correlation between MD and cellularity. Although it is still in an initial phase of development, ex vivo tissue imaging is a promising approach, which offers radiology-pathology correlation in a straightforward and comprehensive manner.

  10. The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study protocol.

    Science.gov (United States)

    van den Bos, W; de Bruin, D M; Muller, B G; Varkarakis, I M; Karagiannis, A A; Zondervan, P J; Laguna Pes, M P; Veelo, D P; Savci Heijink, C D; Engelbrecht, M R W; Wijkstra, H; de Reijke, T M; de la Rosette, J J M C H

    2014-10-29

    Current surgical and ablative treatment options for prostate cancer have a relatively high incidence of side effects, which may diminish the quality of life. The side effects are a consequence of procedure-related damage of the blood vessels, bowel, urethra or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective in destroying tumour cells and harbours the advantage of sparing surrounding tissue and vital structures. The aim of the study is to evaluate the safety and efficacy and to acquire data on patient experience of minimally invasive, transperineally image-guided IRE for the focal ablation of prostate cancer. In this multicentre pilot study, 16 patients with prostate cancer who are scheduled for a radical prostatectomy will undergo an IRE procedure, approximately 30 days prior to the radical prostatectomy. Data as adverse events, side effects, functional outcomes, pain and quality of life will be collected and patients will be controlled at 1 and 2 weeks post-IRE, 1 day preprostatectomy and postprostatectomy. Prior to the IRE procedure and the radical prostatectomy, all patients will undergo a multiparametric MRI and contrast-enhanced ultrasound of the prostate. The efficacy of ablation will be determined by whole mount histopathological examination, which will be correlated with the imaging of the ablation zone. The protocol is approved by the ethics committee at the coordinating centre (Academic Medical Center (AMC) Amsterdam) and by the local Institutional Review Board at the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. This pilot study will determine the safety and efficacy of IRE in the prostate. It will show the radiological and histopathological effects of IRE ablations and it will provide data to construct an accurate treatment planning tool for IRE in prostate tissue. Clinicaltrials.gov database: NCT01790451. Published by the BMJ

  11. Study protocol: a randomized controlled trial investigating the effects of a psychosexual training program for adolescents with autism spectrum disorder

    OpenAIRE

    Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka Tamar; Verhulst, Frank; Maras, Athanasios; Vegt, de, F.

    2015-01-01

    BACKGROUND: Previous research shows that adolescents with autism spectrum disorder (ASD) run several risks in their psychosexual development and that these adolescents can have limited access to reliable information on puberty and sexuality, emphasizing the need for specific guidance of adolescents with ASD in their psychosexual development. Few studies have investigated the effects of psychosexual training programs for adolescents with ASD and to date no randomized controlled trials are avai...

  12. Support and reluctance in the pre-substantive phase of alleged child abuse victim investigative interviews: revised versus standard NICHD protocols.

    Science.gov (United States)

    Ahern, Elizabeth C; Hershkowitz, Irit; Lamb, Michael E; Blasbalg, Uri; Winstanley, Alice

    2014-01-01

    Children's unwillingness to report abuse places them at risk for re-victimization, and interviewers who do not respond sensitively to that unwillingness may increase the likelihood that victims will not disclose abuse. Interviewer support and children's reluctance were examined on a turn-by-turn basis using sequential analyses in 199 forensic interviews of 3- to 13-year-olds who alleged maltreatment. Half of the children were interviewed using the Revised Protocol that emphasized rapport-building (RP), the others using the Standard National Institute of Child Health and Human Development Protocol (SP). When using the RP, interviewers provided proportionally more support than when using the SP, but even when using the RP they did not specifically provide support when children expressed reluctance. The RP promoted immediate cooperation when reluctant utterances were met with support, however, suggesting that supportive statements were valuable. The findings enhance our understanding of children's willingness to participate in investigative interviews and the means through which interviewers can foster the comfort and well-being of young witnesses. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Design of an ex vivo culture system to investigate the effects of shear stress on cardiovascular tissue.

    Science.gov (United States)

    Sucosky, Philippe; Padala, Muralidhar; Elhammali, Adnan; Balachandran, Kartik; Jo, Hanjoong; Yoganathan, Ajit P

    2008-06-01

    Mechanical forces are known to affect the biomechanical properties of native and engineered cardiovascular tissue. In particular, shear stress that results from the relative motion of heart valve leaflets with respect to the blood flow is one important component of their mechanical environment in vivo. Although different types of bioreactors have been designed to subject cells to shear stress, devices to expose biological tissue are few. In an effort to address this issue, the aim of this study was to design an ex vivo tissue culture system to characterize the biological response of heart valve leaflets subjected to a well-defined steady or time-varying shear stress environment. The novel apparatus was designed based on a cone-and-plate viscometer. The device characteristics were defined to limit the secondary flow effects inherent to this particular geometry. The determination of the operating conditions producing the desired shear stress profile was streamlined using a computational fluid dynamic (CFD) model validated with laser Doppler velocimetry. The novel ex vivo tissue culture system was validated in terms of its capability to reproduce a desired cone rotation and to maintain sterile conditions. The CFD results demonstrated that a cone angle of 0.5 deg, a cone radius of 40 mm, and a gap of 0.2 mm between the cone apex and the plate could limit radial secondary flow effects. The novel cone-and-plate permits to expose nine tissue specimens to an identical shear stress waveform. The whole setup is capable of accommodating four cone-and-plate systems, thus concomitantly subjecting 36 tissue samples to desired shear stress condition. The innovative design enables the tissue specimens to be flush mounted in the plate in order to limit flow perturbations caused by the tissue thickness. The device is capable of producing shear stress rates of up to 650 dyn cm(-2) s(-1) (i.e., maximum shear stress rate experienced by the ventricular surface of an aortic valve leaflet

  14. In vitro and in vivo investigation on genomic stability of Salmonella enterica Typhimurium DT41 obtained from broiler breeders in Denmark

    DEFF Research Database (Denmark)

    Barua, Himel; Lindblom, Ina Lucilia; Bisgaard, Magne

    2013-01-01

    Salmonella enterica serovar Typhimurium phage type DT41 has previously been identified from salmonella-positive broiler breeder flocks in Denmark and isolates obtained from different flocks have demonstrated major diversity by multiple-locus variable-number tandem-repeats analysis (MLVA) typing...... and human origin, respectively. The in vitro experiment demonstrated that DT41 survived more than 6 months in feed-pellets at 20 °C whereas the survival in dust was less than 4 weeks. Infection pattern and excretion varied for the poultry and human strain and birds of different age groups as revealed...... by the in vivo experiment. Genetic stability of cultures obtained from the in vitro and in vivo survival/passage was investigated by plasmid profiling, pulsed-field gel electrophoresis (PFGE) and MLVA. The results of plasmid profiling and PFGE demonstrated genomic stability of all but one strain kept in dust...

  15. Bioremediation protocols

    National Research Council Canada - National Science Library

    Sheehan, David

    1997-01-01

    ..., .. . . . . .. ,. . . .. . . . . . . . .. . . . . .. . . .. . .. 3 2 Granular Nina Sludge Christiansen, Consortia lndra for Bioremediation, M. Mathrani, and Birgitte K. Ahring . 23 PART II PROTOCOLS...

  16. Once-daily propranolol extended-release tablet dosage form: formulation design and in vitro/in vivo investigation.

    Science.gov (United States)

    Huang, Yaw-Bin; Tsai, Yi-Hung; Yang, Wan-Chiech; Chang, Jui-Sheng; Wu, Pao-Chu; Takayama, Kozo

    2004-11-01

    The purpose of this study was to develop and optimize the propranolol once-daily extended release formulations containing HPMC, Microcrystalline cellulose (MCC) and lactose. In vitro studies, the response surface methodology and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals. The constrained mixture experimental design was used to prepare systematic model formulations, which were composed of three formulation variables: the content of HPMC (X(1)) MCC (X(2)) and lactose (X(3)). The drug release percent at 1.5, 4, 8, 14 and 24 h were the target responses and were restricted to 15-30, 35-55, 55-75, 75-90 and 90-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrix tablets followed non-Fickian diffusion. In the vivo study, the MRT was prolonged for matrix tablets when compared with commercial immediate release tablets. Furthermore, a linear relationship between in vitro dissolution and in vivo absorption was observed in the beagle dogs.

  17. In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E PO as drug particle coating agent in orally disintegrating tablets.

    Science.gov (United States)

    Drašković, Milica; Medarević, Djordje; Aleksić, Ivana; Parojčić, Jelena

    2017-05-01

    Considering that bitter taste of drugs incorporated in orally disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy, it is of the utmost importance to achieve successful taste-masking. The evaluation of taste-masking effectiveness is still a major challenge. The objective of this study was to mask bitter taste of the selected model drugs by drug particle coating with Eudragit ® E PO, as well as to evaluate taste-masking effectiveness of prepared ODTs using compendial dissolution testing, dissolution in the small-volume shake-flask assembly and trained human taste panel. Model drugs were coated in fluidized bed. Disintequik™ ODT was used as a novel co-processed excipient for ODT preparation. Selected formulations were investigated in vitro and in vivo using techniques for taste-masking assessment. Significantly slower drug dissolution was observed from tablets with coated drug particles during the first 3 min of investigation. Results of in vivo taste-masking assessment demonstrated significant improvement in drug bitterness suppression in formulations with coated drug. Strong correlation between the results of drug dissolution in the small-volume shake-flask assembly and in vivo evaluation data was established (R ≥ 0.970). Drug particle coating with Eudragit ® E PO can be a suitable approach for bitter taste-masking. Strong correlation between in vivo and in vitro results implicate that small-volume dissolution method may be used as surrogate for human panel taste-masking assessment, in the case of physical taste-masking approach application.

  18. Sevoflurane-induced Preconditioning Impact of Protocol and Aprotinin Administration on Infarct Size and Endothelial Nitric-Oxide Synthase Phosphorylation in the Rat Heart In Vivo

    NARCIS (Netherlands)

    Fräßdorf, Jan; Huhn, Ragnar; Weber, Nina C.; Ebel, Dirk; Wingert, Nadja; Preckel, Benedikt; Toma, Octavian; Schlack, Wolfgang; Hollmann, Markus W.

    2010-01-01

    Background Sevoflurane induces preconditioning (SevoPC) 1 he effect of aprotinin and the involvement of endothelial nitric-oxide synthase (NOS) on SevoPC are unknown We investigated (1) whether SevoPC is strengthened by multiple preconditioning cycles (2) whether SevoPC is blocked by aprotinin, and

  19. An investigation into the role of alcohol in self-harm in rural Sri Lanka: a protocol for a multimethod, qualitative study

    DEFF Research Database (Denmark)

    Sørensen, Jane Brandt; Rheinländer, Thilde; Sørensen, Birgitte Refslund

    2014-01-01

    Introduction: Sri Lanka has one of the highest suicide and self-harm rates in the world and although alcohol has been found to be a risk factor for self-harm in Sri Lanka, we know little about the connection between the two. This paper comprises a protocol for a qualitative study investigating...... alcohol’s role in selfharm in rural Sri Lanka at three levels: the individual, community and policy level. The analysis will bring new understanding of the link between alcohol and self-harm in Sri Lanka, drawing on structural, cultural and social concepts. It will equip researchers, health systems...... and policy makers with vital information for developing strategies to address alcohol-related problems as they relate to self-harm. Methods and analysis: To capture the complexity of the link between alcohol and self-harm in the Anuradhapura district in the North Central Province in Sri Lanka, qualitative...

  20. An investigation of somatosensory profiles in work related upper limb disorders: a case-control observational study protocol.

    LENUS (Irish Health Repository)

    Moloney, Niamh

    2010-01-01

    BACKGROUND: Work related upper limb disorders constitute 45% of all occupational diseases and are a significant public health problem. A subgroup, non specific arm pain (NSAP), remains elusive in terms of understanding its pathophysiological mechanisms with its diagnosis based on the absence of specific clinical findings. One commonly proposed theory is that a neural tissue disorder is the primary dysfunction in NSAP and findings from previous studies lend some support to this theory. However, it is not clear if changes identified are simply a consequence of ongoing pain rather than due to specific neural changes. The presence of neuropathic pain has been investigated in several other musculoskeletal conditions but currently, there is no specific diagnostic tool or gold standard which permits an unequivocal diagnosis of neuropathic pain. The purpose of this study is to further describe the somatosensory profiles in patients with NSAP and to compare these profiles to a group of patients with MRI confirmed cervical radiculopathy who have been previously classified as having neuropathic pain. METHODS\\/DESIGN: Three groups of participants will be investigated: Groups 1 and 2 will be office workers with either NSAP or cervical radiculopathy and Group 3 will be a control group of non office workers without upper limb pain. Participants will undergo a clinical assessment, pain questionnaires (LANSS, Short Form McGill, DASH and TSK) and quantitative sensory testing comprising thermal detection and pain thresholds, vibration thresholds and pressure pain thresholds. DISCUSSION: The spectrum of clinically suspected neuropathic pain ranges from more obvious conditions such as trigeminal neuralgia to those with vague signs of nerve disorder such as NSAP. A thorough description of the somatosensory profiles of NSAP patients and a comparison with a more defined group of patients with evidence of neuropathic pain will help in the understanding of underlying neurophysiology in

  1. Experimental protocol of a randomized controlled clinical trial investigating exercise, subclinical atherosclerosis, and walking mobility in persons with multiple sclerosis.

    Science.gov (United States)

    Griffith, Garett; Klaren, Rachel E; Motl, Robert W; Baynard, Tracy; Fernhall, Bo

    2015-03-01

    This randomized controlled trial (RCT) will investigate the effects of a home-based aerobic exercise training regimen (i.e., cycle ergometry) on subclinical atherosclerosis and walking mobility in persons with multiple sclerosis (MS) and minimal disability. This RCT will recruit 54 men and women who have an Expanded Disability Status Scale characteristic of the 1st stage of MS (i.e., 0-4.0) to participate in a 3 month exercise or stretching intervention, with assessments of subclinical atherosclerosis and walking mobility conducted at baseline, week 6 (midpoint), and week 12 (conclusion) of the program. The exercise intervention will consist of 3 days/week of cycling, with a gradual increase of duration followed by an increase in intensity across the 3 month period. The attention-control condition will incorporate stretching activities and will require the same contact time commitment as the exercise condition. Both study groups will participate in weekly video chat sessions with study personnel in order to monitor and track program adherence. Primary outcomes will consist of assessments of vascular structure and function, as well as several walking tasks. Additional outcomes will include questionnaires, cardiorespiratory fitness assessment, and a 1-week free-living physical activity assessment. This investigation will increase understanding of the role of aerobic exercise as part of a treatment plan for managing subclinical atherosclerosis and improving walking mobility persons in the 1st stage of MS. Overall, this study design has the potential to lead to effective aerobic exercise intervention strategies for this population and improve program adherence. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Dynamic longitudinal investigation of individual nerve endings in the skin of anesthetized mice using in vivo two-photon microscopy

    Science.gov (United States)

    Yuryev, Mikhail; Khiroug, Leonard

    2012-04-01

    Visualization of individual cutaneous nerve endings has previously relied on laborious procedures of tissue excision, fixation, sectioning and staining for light or electron microscopy. We present a method for non-invasive, longitudinal two-photon microscopy of single nerve endings within the skin of anesthetized transgenic mice. Besides excellent signal-to-background ratio and nanometer-scale spatial resolution, this method offers time-lapse ``movies'' of pathophysiological changes in nerve fine structure over minutes, hours, days or weeks. Structure of keratinocytes and dermal matrix is visualized simultaneously with nerve endings, providing clear landmarks for longitudinal analysis. We further demonstrate feasibility of dissecting individual nerve fibers with infra-red laser and monitoring their degradation and regeneration. In summary, our excision-free optical biopsy technique is ideal for longitudinal microscopic analysis of animal skin and skin innervations in vivo and can be applied widely in preclinical models of chronic pain, allergies, skin cancers and a variety of dermatological disorders.

  3. Investigating medical decision-making capacity in patients with cognitive impairment using a protocol based on linguistic features.

    Science.gov (United States)

    Tallberg, Ing-Mari; Stormoen, Sara; Almkvist, Ove; Eriksdotter, Maria; Sundström, Erik

    2013-10-01

    A critical question is whether cognitively impaired patients have the competence for autonomous decisions regarding participation in clinical trials. The present study aimed to investigate medical decision-making capacity by use of a Swedish linguistic instrument for medical decision-making (LIMD) in hypothetical clinical trials in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Three comparable groups (age, education) participated in the study: AD (n = 20; MMSE: 24.1 ± 3.3) and MCI (n = 22; MMSE: 26.7 ± 2.4) patients and healthy controls (n = 37; MMSE: 29.1 ± 1.0). Medical decision-making capacity was operationalized as answers to questions regarding participation in three hypothetical clinical trials. Answers were scored regarding comprehension, evaluation and intelligibility of decisions, and a total LIMD score was used as the measure of medical decision-making ability. Groups differed significantly in LIMD with AD patients performing worst and MCI poorer than the control group. A strong association was found between all LIMD scores and diagnosis which supported the assertion that LIMD as it is designed is a one-dimensional instrument of medical decision-making capacity (MDMC). The results indicate that a fundamental communicative ability has an impact on the competence for autonomous decisions in cognitive impairment. © 2013 The Scandinavian Psychological Associations.

  4. An investigation of the impact of using different methods for network meta-analysis: a protocol for an empirical evaluation.

    Science.gov (United States)

    Karahalios, Amalia Emily; Salanti, Georgia; Turner, Simon L; Herbison, G Peter; White, Ian R; Veroniki, Areti Angeliki; Nikolakopoulou, Adriani; Mckenzie, Joanne E

    2017-06-24

    Network meta-analysis, a method to synthesise evidence from multiple treatments, has increased in popularity in the past decade. Two broad approaches are available to synthesise data across networks, namely, arm- and contrast-synthesis models, with a range of models that can be fitted within each. There has been recent debate about the validity of the arm-synthesis models, but to date, there has been limited empirical evaluation comparing results using the methods applied to a large number of networks. We aim to address this gap through the re-analysis of a large cohort of published networks of interventions using a range of network meta-analysis methods. We will include a subset of networks from a database of network meta-analyses of randomised trials that have been identified and curated from the published literature. The subset of networks will include those where the primary outcome is binary, the number of events and participants are reported for each direct comparison, and there is no evidence of inconsistency in the network. We will re-analyse the networks using three contrast-synthesis methods and two arm-synthesis methods. We will compare the estimated treatment effects, their standard errors, treatment hierarchy based on the surface under the cumulative ranking (SUCRA) curve, the SUCRA value, and the between-trial heterogeneity variance across the network meta-analysis methods. We will investigate whether differences in the results are affected by network characteristics and baseline risk. The results of this study will inform whether, in practice, the choice of network meta-analysis method matters, and if it does, in what situations differences in the results between methods might arise. The results from this research might also inform future simulation studies.

  5. An investigation into the depth of penetration of low level laser therapy through the equine tendon in vivo

    Directory of Open Access Journals (Sweden)

    Ryan Teresa

    2007-05-01

    Full Text Available Abstract Low level laser therapy (LLLT is frequently used in the treatment of wounds, soft tissue injury and in pain management. The exact penetration depth of LLLT in human tissue remains unspecified. Similar uncertainty regarding penetration depth arises in treating animals. This study was designed to test the hypothesis that transmission of LLLT in horses is increased by clipping the hair and/or by cleaning the area to be treated with alcohol, but is unaffected by coat colour. A LLLT probe (810 nm, 500 mW was applied to the medial aspect of the superficial flexor tendon of seventeen equine forelimbs in vivo. A light sensor was applied to the lateral aspect, directly opposite the laser probe to measure the amount of light transmitted. Light transmission was not affected by individual horse, coat colour or leg. However, it was associated with leg condition (F = 4.42, p = 0.0032. Tendons clipped dry and clipped and cleaned with alcohol, were both associated with greater transmission of light than the unprepared state. Use of alcohol without clipping was not associated with an increase in light transmission. These results suggest that, when applying laser to a subcutaneous structure in the horse, the area should be clipped and cleaned beforehand.

  6. The pathogenesis of Randall's plaque: a papilla cartography of Ca compounds through an ex vivo investigation based on XANES spectroscopy.

    Science.gov (United States)

    Carpentier, Xavier; Bazin, Dominique; Jungers, Paul; Reguer, Solenn; Thiaudière, Dominique; Daudon, Michel

    2010-05-01

    At the surface of attached kidney stones, a particular deposit termed Randall's plaque (RP) serves as a nucleus. This structural particularity as well as other major public health problems such as diabetes type-2 may explain the dramatic increase in urolithiasis now affecting up to 20% of the population in the industrialized countries. Regarding the chemical composition, even if other phosphate phases such as whitlockite or brushite can be found as minor components (less than 5%), calcium phosphate apatite as well as amorphous carbonated calcium phosphate (ACCP) are the major components of most RPs. Through X-ray absorption spectroscopy performed at the Ca K-absorption edge, a technique specific to synchrotron radiation, the presence and crystallinity of the Ca phosphate phases present in RP were determined ex vivo. The sensitivity of the technique was used as well as the fact that the measurements can be performed directly on the papilla. The sample was stored in formol. Moreover, a first mapping of the chemical phase from the top of the papilla to the deep medulla is obtained. Direct structural evidence of the presence of ACCP as a major constituent is given for the first time. This set of data, coherent with previous studies, shows that this chemical phase can be considered as one precursor in the genesis of RP.

  7. Cryptographic Protocols:

    DEFF Research Database (Denmark)

    Geisler, Martin Joakim Bittel

    implemented the comparison protocol in Java and benchmarks show that is it highly competitive and practical. The biggest contribution of this dissertation is a general framework for secure multiparty computation. Instead of making new ad hoc implementations for each protocol, we want a single and extensible...... real-world cases, a large probability of being caught is sufficient to prevent the adversary from trying to cheat. We show how to compile a passively secure protocol for honest majority into a protocol that is secure against covert attacks, again for honest majority. The transformed protocol catches...... cheating with probability 1/4 . Though we present no implementation of this compiler, we believe it will be very efficient and practical to implement using, say, VIFF. The cost of the modified protocol is essentially twice that of the original plus an overhead that only depends on the number of inputs. We...

  8. The Institution of a Standardized Investigation Protocol for Sudden Infant Death in the Eastern Metropole, Cape Town, South Africa*,†,‡

    Science.gov (United States)

    Dempers, Johan J.; Coldrey, Jean; Burger, Elsie H.; Thompson, Vonita; Wadee, Shabbir A.; Odendaal, Hein J.; Sens, Mary Ann; Randall, Brad B.; Folkerth, Rebecca D.; Kinney, Hannah C.

    2017-01-01

    The rate for the sudden infant death syndrome (SIDS) in Cape Town, South Africa, is estimated to be among the highest in the world (3.41/1000 live births). In several of these areas, including those of extreme poverty, only sporadic, nonstandardized infant autopsy, and death scene investigation (DSI) occurred. In this report, we detail a feasibility project comprising 18 autopsied infants with sudden and unexpected death whose causes of death were adjudicated according to the 1991 NICHD definitions (SIDS, n = 7; known cause of death, n = 7; and unclassified, n = 4). We instituted a standardized autopsy and infant DSI through a collaborative effort of local forensic pathology officers and clinical providers. The high standard of forensic investigation met international standards, identified preventable disease, and allowed for incorporation of research. We conclude that an effective infant autopsy and DSI protocol can be established in areas with both high sudden unexpected infant death, and elsewhere. (SUID)/SIDS risk and infrastructure challenges. PMID:27677096

  9. Non-Invasive Assessment of Skin Barrier Properties: Investigating Emerging Tools for In Vitro and In Vivo Applications

    Directory of Open Access Journals (Sweden)

    Emer Duffy

    2017-10-01

    Full Text Available There is increasing interest in the development of non-invasive tools for studying the properties of skin, due to the potential for non-destructive sampling, reduced ethical concerns and the potential comparability of results in vivo and in vitro. The present research focuses on the use of a range of non-invasive approaches for studying skin and skin barrier properties in human skin and human skin equivalents (HSE. Analytical methods used include pH measurements, electrical sensing of the epidermis and detection of volatile metabolic skin products. Standard probe based measurements of pH and the tissue dielectric constant (TDC are used. Two other more novel approaches that utilise wearable platforms are also demonstrated here that can assess the electrical properties of skin and to profile skin volatile species. The potential utility of these wearable tools that permit repeatability of testing and comparability of results is considered through application of our recently reported impedance-based tattoo sensors and volatile samplers on both human participants and HSEs. The HSE exhibited a higher pH (6.5 and TDC (56 than human skin (pH 4.9–5.6, TDC 29–36, and the tattoo sensor revealed a lower impedance signal for HSEs, suggesting the model could maintain homeostasis, but in a different manner to human skin, which demonstrated a more highly resistive barrier. Characterisation of volatiles showed a variety of compound classes emanating from skin, with 16 and 27 compounds identified in HSEs and participants respectively. The continuing development of these tools offers potential for improved quality and relevance of data, and potential for detection of changes that are undetectable in traditional palpable and visual assessments, permitting early detection of irritant reactions.

  10. Morphological and functional properties of the conducting human airways investigated by in vivo CT and in vitro MRI.

    Science.gov (United States)

    Van de Moortele, Tristan; Wendt, Christine H; Coletti, Filippo

    2017-11-02

    The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyze CT scans of a cohort of healthy subjects and obtain comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle. While some of the geometrical parameters (such as the child-to-parent branch diameter ratio) are found to be in line with accepted values, for others (such as the branch length-to-diameter ratio) our findings challenge the common assumptions. We also evaluate several metrics of self-similarity, including the fractal dimension of the airway tree. Additionally, we use phase-contrast magnetic resonance imaging (MRI) to obtain the volumetric flow field in the 3D printed airway model of one of the subjects during steady inhalation. This is used to relate structural and functional parameters and, in particular, to close the power-law relationship between branch flow rate and diameter. The diameter exponent is found to be significantly lower than in the usually assumed Poiseuille regime, which we attribute to the strong secondary (i.e. transverse) velocity component. The strength of the secondary velocity with respect to the axial component exceeds the levels found in idealized airway models, and persists within the first seven generations. Copyright © 2017, Journal of Applied Physiology.

  11. Prevalence of middle mesial canals in mandibular molars after guided troughing under high magnification: an in vivo investigation.

    Science.gov (United States)

    Azim, Adham A; Deutsch, Allan S; Solomon, Charles S

    2015-02-01

    A limited number of in vivo studies have discussed the prevalence of middle mesial canals in root canal systems of mandibular molars. The reported results have varied between 1% and 25%, with no detailed description of the depth and direction of troughing needed to identify such small canal orifices. The objective of the present study was to determine (1) the prevalence of a middle mesial canal before and after troughing by using a standardized troughing technique, (2) the pathway of the middle mesial canal in relation to the mesiobuccal (MB) and mesiolingual (ML) canals, and (3) its correlation with the patient's age. Ninety-one mandibular molars from 87 patients were included in this study. The patient's age and tooth number were recorded. After access cavity preparation, a standardized troughing technique was performed between MB and ML canals to search for a middle mesial canal by using a dental operating microscope. If a middle mesial canal was located, it was recorded as separate or as joining the MB or the ML canals. Results were statistically analyzed by using Z test and logistic regression. A middle mesial canal was found in 42 of 91 mandibular molars (46.2%). Six middle mesial canals were located after conventional access preparation (6.6%). The other 36 were located after standardized troughing (39.6%). The results were statistically significant (P magnification, troughing, and patient's age appeared to be determining factors in accessing the middle mesial canal. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. (dtltt) protocol

    African Journals Online (AJOL)

    2013-03-01

    Mar 1, 2013 ... STLODGSTT protocol uses static value of threshold bandwidth to allocate available bandwidth to the asynchronous traffic, as such, the ... 12, 13 ] SAFENET [14], Manufacturing Automation. Protocol (MAP) [15], High-Speed ... the threshold bandwidth used in allocating available bandwidth to the n heavily ...

  13. Implications of adipose-derived stromal cells in a 3D culture system for osteogenic differentiation: an in vitro and in vivo investigation.

    Science.gov (United States)

    Shen, Francis H; Werner, Brian C; Liang, Haixiang; Shang, Hulan; Yang, Ning; Li, Xudong; Shimer, Adam L; Balian, Gary; Katz, Adam J

    2013-01-01

    Healthy mammalian cells in normal tissues are organized in complex three-dimensional (3D) networks that display nutrient and signaling gradients. Conventional techniques that grow cells in a 2D monolayer fail to reproduce the environment that is observed in vivo. In recent years, 3D culture systems have been used to mimic tumor microenvironments in cancer research and to emulate embryogenesis in stem cell cultures. However, there have been no studies exploring the ability for adipose-derived stromal (ADS) cells in a 3D culture system to undergo osteogenic differentiation. To characterize and investigate the in vitro and in vivo potential for human ADS cells in a novel 3D culture system to undergo osteogenic differentiation. Basic science and laboratory study. Human ADS cells were isolated and prepared as either a 2D monolayer or 3D multicellular aggregates (MAs). Multicellular aggregates were formed using the hanging droplet technique. Cells were treated in osteogenic medium in vitro, and cellular differentiation was investigated using gene expression, histology, and microCT at 1-, 2-, and 4-week time points. In vivo investigation involved creating a muscle pouch by developing the avascular muscular interval in the vastus lateralis of male athymic rats. Specimens were then pretreated with osteogenic medium and surgically implanted as (1) carrier (Matrigel) alone (control), (2) carrier with human ADS cells in monolayer, or (3) human ADS cells as MAs. In vivo evidence of osteogenic differentiation was evaluated with micro computed tomography and histologic sectioning at a 2-week time point. Human ADS cells cultured by the hanging droplet technique successfully formed MAs at the air-fluid interface. Adipose-derived stromal cells cultured in monolayer or as 3D MAs retain their ability to self-replicate and undergo multilineage differentiation as confirmed by increased runx2/Cbfa2, ALP, and OCN and increased matrix mineralization on histologic sectioning

  14. Application of the holographic interference microscope for investigation of ozone therapy influence on blood erythrocytes of patients in vivo

    Science.gov (United States)

    Tishko, Tatyana V.; Titar, V. P.; Barchotkina, T. M.; Tishko, D. N.

    2004-09-01

    The holographic methods of phase micro-objects visualization (the holographic phase contrast method and the method of holographic interferometry) are considered. Comparative analysis of classical and holographic methods in microscopy of phase micro-objects is carried out. An arrangement of the holographic interference microscope realizing the holographic methods and experimental results of 3-D imaging of native blood erythrocytes are presented. It is shown that 3-D morphology of blood erythrocytes reflects and determines the state of a human organism and those different physical and chemical factors and internal pathologies influence erythrocytes morphology. The holographic interference microscope was used for investigation of ozone therapy influence on human blood erythrocytes. Blood samples of 60 patients of different age with neurosensoric hardness of hearing before and after ozone therapy were investigated. It was shown that all patients have changed erythrocytes mrophology. Ozone therapy treatment results in normalization of erythrocytes morphology of patients.

  15. Quantification of functional brace forces for posterior cruciate ligament injuries on the knee joint: an in vivo investigation.

    Science.gov (United States)

    LaPrade, Robert F; Smith, Sean D; Wilson, Katharine J; Wijdicks, Coen A

    2015-10-01

    Counteracting posterior translation of the tibia with an anterior force on the posterior proximal tibia has been demonstrated clinically to improve posterior knee laxity following posterior cruciate ligament (PCL) injury. This study quantified forces applied to the posterior proximal tibia by two knee braces designed for treatment of PCL injuries. The forces applied by two knee braces to the posterior proximal tibia and in vivo three-dimensional knee kinematics of six adult, male, healthy volunteer subjects (mean ± standard deviation: height, 182.5 ± 5.2 cm; body mass, 83.2 ± 9.3 kg; body mass index, 24.9 ± 1.5 kg/m(2); age, 25.8 ± 2.9 years) were measured using a custom pressure mapping technique and traditional surface marker motion capture techniques, while subjects performed three functional activities. The activities included seated unloaded knee flexion, squatting, and stair descent in a new generation dynamic force (DF) PCL brace and a static force (SF) PCL brace. During unloaded flexion at the lowest force level setting, the force applied by the DF brace increased as a function of flexion angle (slope = 0.7 N/°; p brace effect. Force applied by the SF brace did not significantly change as a function of flexion angle (slope = 0.0 N/°; n.s.). By 45° of flexion, the average force applied by the DF brace (48.1 N) was significantly larger (p brace (25.0 N). The difference in force continued to increase as flexion angle increased. During stair descent, average force (mean ± standard deviation) at toe off was significantly higher (p = 0.013) for the DF brace (78.7 ± 21.6 N) than the SF brace (37.3 ± 7.2 N). Similar trends were observed for squatting and for the higher force level settings. The DF brace applied forces to the posterior proximal tibia that dynamically increased with increased flexion angle. Additionally, the DF brace applied significantly larger forces at higher flexion angles compared to the SF brace

  16. Investigation of protocols to extraction and quantification of folates in vegetables matrices split into liquor and fiber fraction using factorial design.

    Science.gov (United States)

    Prado de Paiva, Emmanuela; Anderson de Azevedo Filho, Clayton; Ferreira, Sabrina Gomes; Stamford, Tânia Lucia Montenegro; da Paixão, Jose Almiro

    2012-10-19

    The main protocols of extraction were investigated for the six folate forms in vegetable matrices, treated in two fractions, liquor and fiber. In a pilot study, it was used ammonium acetate added of 2-mercaptoetanol and ascorbic acid as extraction solution. The condition of use of protease and folate conjugase was evaluated, besides alternative treatments without enzyme use. Based on the results of this stage, it was built the factorial design 2(4), with three replications at the central point, using the following variables: temperature, time for reaction, molar concentration of the extraction solution and ratio sample/solution as independent variables and dependent variable, the amount of each folate form extracted as well as spectral and chromatographic parameters. In the pilot study it was verified that the enzyme use can cause an increase in the variability of the folate content, which enabled to build the factorial design without the enzyme use. The binomial time and temperature showed greatest impact on the extraction profile, besides high concentrations of ammonium acetate resulting in bifurcation of some peaks. 5-Methyltetrahydrofolate was extracted primordially in the liquor fraction, indicating that this treatment on the matrix provoked suitable extraction condition to this folate. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Investigation of in vitro and in vivo antioxidant activities of flavonoids rich extract from the berries of Rhodomyrtus tomentosa(Ait.) Hassk.

    Science.gov (United States)

    Wu, Pingping; Ma, Guangzhi; Li, Nianghui; Deng, Qian; Yin, Yanyan; Huang, Ruqiang

    2015-04-15

    This study investigated the in vitro and in vivo antioxidant activities of the flavonoids rich extract from Rhodomyrtus tomentosa Hassk (R. tomentosa) berries. The in vitro antioxidant assay demonstrated that the flavonoids rich extract (62.09% rutin equivalent) extracted by ethanol and purified by AB-8 macroporous resin was strong in reducing power, superoxide radical, hydroxyl radical and DPPH radical scavenging activity, as well as inhibiting lipid peroxidation. In the in vivo assays, the flavonoids rich extract significantly enhanced the activities of antioxidant enzymes in serums of mice after they were administered with the extract. The results suggested that the flavonoids rich extract from R. tomentosa fruits possesses potent antioxidant properties. In addition, the chemical compositions of flavonoids rich extract were identified by UPLC-TOF-MS/MS. Six flavonoids were tentatively identified as myricetin, quercetin, dihydromyricetin, kaempferol, quercetin 7,4'-diglucoside and vitexin. Therefore, R. tomentosa berries could be used as a new source of antioxidant ingredient. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [{sup 123}I]FP-CIT and a dedicated small animal SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf [Heinrich-Heine University, Clinic of Nuclear Medicine, Duesseldorf (Germany); Schramm, Nils [Research Center Juelich, Central Laboratory for Electronics, Juelich (Germany)

    2005-03-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [{sup 123}I]FP-CIT. [{sup 123}I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [{sup 123}I]FP-CIT scans with bone metabolism and perfusion scans obtained with {sup 99m}Tc-DPD and {sup 99m}Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [{sup 123}I]FP-CIT scans with images of brain perfusion obtained with {sup 99m}Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''{sub 3}) of 0.24{+-}0.26 (mean {+-} SD) and 1.09{+-}0.42, respectively (ttest, two-tailed, p<0.0001). Cortical V''{sub 3} values amounted to 0.05{+-}0.28 (methylphenidate) and 0.3{+-}0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [{sup 123}I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [{sup 123}I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and

  19. In-vivo laser induced urethral stricture animal model for investigating the potential of LDR-brachytherapy

    Science.gov (United States)

    Sroka, Ronald; Lellig, Katja; Bader, Markus; Stief, Christian; Weidlich, Patrick; Wechsel, G.; Assmann, Walter; Becker, R.; Fedorova, O.; Khoder, Wael

    2015-02-01

    Purpose: Treatment of urethral strictures is a major challenge in urology. For investigation of different treatment methods an animal model was developed by reproducible induction of urethral strictures in rabbits to mimic the human clinical situation. By means of this model the potential of endoluminal LDR brachytherapy using β-irradiation as prophylaxis of recurrent urethral strictures investigated. Material and Methods: A circumferential urethral stricture was induced by energy deposition using laser light application (wavelength λ=1470 nm, 10 W, 10 s, applied energy 100 J) in the posterior urethra of anaesthetized New Zealand White male rabbits. The radial light emitting fiber was introduced by means of a children resectoscope (14F). The grade of urethral stricture was evaluated in 18 rabbits using videourethroscopy and urethrography at day 28 after stricture induction. An innovative catheter was developed based on a β-irradiation emitting foil containing 32P, which was wrapped around the application system. Two main groups (each n=18) were separated. The "internal urethrotomy group" received after 28days of stricture induction immediately after surgical urethrotomy of the stricture the radioactive catheter for one week in a randomized, controlled and blinded manner. There were 3 subgroups with 6 animals each receiving 0 Gy, 15 Gy and 30 Gy. In contrast animals from the "De Nuovo group" received directly after the stricture induction (day 0) the radioactive catheter also for the duration of one week divided into the same dose subgroups. In order to determine the radiation tolerance of the urethral mucosa, additional animals without any stricture induction received a radioactive catheter applying a total dose of 30 Gy (n=2) and 15 Gy (n=1). Cystourethrography and endoscopic examination of urethra were performed on all operation days for monitoring treatment progress. Based on these investigation a classification of the stricture size was performed and

  20. Post-injury ex vivo model to investigate effects and toxicity of pharmacological treatment in rings of rabbit aortic vessels.

    Science.gov (United States)

    Finking, G; Wolkenhauer, M; Lenz, C; Hanke, H

    2000-01-01

    Animal experiments are widely accepted in arteriosclerosis research. The aim of the present study was to establish an organ culture model (rings of rabbit aortic vessels) to investigate inhibitory estrogen effects on post injury neointima formation in the vessel wall and to examine whether these effects are cytotoxic. Estrogens are used for secondary prevention of atherosclerosis in postmenopausal women (estrogen replacement therapy/ERT). Phytoestrogens as well as the ovarian 17 beta-estradiol have been demonstrated to inhibit proliferation and migration of vascular smooth muscle cells which are key events in atherogenesis and restenosis after coronary angioplasty. In situ endothelial denudation of the thoracic and abdominal aorta was performed in female rabbits by a 3F Fogarty catheter. Segments of 5 mm were randomized in groups of n = 12 and held in culture. 17 beta-estradiol, Genistein and Daidzein were applied in concentrations of 20 microM, 30 microM, and 40 microM. Groups without estrogen treatment served as controls. The segments were investigated after 21 days. Afterwards, 3 further groups (n = 12) were held with the lowest concentrations of 17 beta-estradiol or the two phytoestrogens having been evaluated to inhibit the neointima formation significantly. After 21 days of treatment these sections were held in medium only for another 7 days to proof whether these segments were still able to proliferate. A denuded control group was held in medium only over 28 days. Compared to controls, 30 microM 17 beta-estradiol, 20 microM Genistein, and 40 microM Daidzein inhibited neointima formation significantly over 21 days. After another 7 days of cultivation in medium only the amount of neointima formation was comparable to that of non-estrogen-treated controls after 21 days. We therefore suggest that the demonstrated inhibitory effect is not explained by toxicity. In conclusion, by the use of this organ culture model it was possible to demonstrate non-toxic post

  1. Investigation of left and right lateral fluid percussion injury in C57BL6/J mice: In vivo functional consequences.

    Science.gov (United States)

    Schurman, Lesley D; Smith, Terry L; Morales, Anthony J; Lee, Nancy N; Reeves, Thomas M; Phillips, Linda L; Lichtman, Aron H

    2017-07-13

    Although rodent models of traumatic brain injury (TBI) reliably produce cognitive and motor disturbances, behavioral characterization resulting from left and right hemisphere injuries remains unexplored. Here we examined the functional consequences of targeting the left versus right parietal cortex in lateral fluid percussion injury, on Morris water maze (MWM) spatial memory tasks (fixed platform and reversal) and neurological motor deficits (neurological severity score and rotarod). In the MWM fixed platform task, right lateral injury produced a small delay in acquisition rate compared to left. However, injury to either hemisphere resulted in probe trial deficits. In the MWM reversal task, left-right performance deficits were not evident, though left lateral injury produced mild acquisition and probe trial deficits compared to sham controls. Additionally, left and right injury produced similar neurological motor task deficits, impaired righting times, and lesion volumes. Injury to either hemisphere also produced robust ipsilateral, and modest contralateral, morphological changes in reactive microglia and astrocytes. In conclusion, left and right lateral TBI impaired MWM performance, with mild fixed platform acquisition rate differences, despite similar motor deficits, histological damage, and glial cell reactivity. Thus, while both left and right lateral TBI produce cognitive deficits, laterality in mouse MWM learning and memory merits consideration in the investigation of TBI-induced cognitive consequences. Copyright © 2017. Published by Elsevier B.V.

  2. Road Safety Data, Collection, Transfer and Analysis DaCoTa. Workpackage 2, Developing a Pan-European In-depth Accident Investigation Network: Deliverable 2.3: Training package including training manual and Draft Protocols.

    NARCIS (Netherlands)

    Fagerlind, H. Armstrong, J. Atala, D. Dodson, E. Talbot, R. Hill, J. Roynard, M. Martensen, H. Jänsch, M. Margaritis, D. Ocampo Sanchez, A. Peez, J. Ferrer, A. Elslande, P. van Perrin, C. Hermitte, T. Giustiniani, G. & Davidse, R.

    2015-01-01

    This deliverable is intended to collate the DaCoTA training manual and draft protocols for in-depth road accident investigations in Europe. This deliverable aims at producing a document that will be used in the training of new and previously experienced teams in the realm of in depth accident data

  3. In vivo Investigation of Anti-diabetic Properties of Ripe Onion Juice in Normal and Streptozotocin-induced Diabetic Rats

    Science.gov (United States)

    Lee, Chul-Won; Lee, Hyung-Seok; Cha, Yong-Jun; Joo, Woo-Hong; Kang, Dae-Ook; Moon, Ja-Young

    2013-01-01

    The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is “Black Onion Extract”) were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyper-glycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product “Black Onion Extract” may possess anti-hyperglycemic potential in diabetes. PMID:24471128

  4. Ex vivo investigation on the postoperative integrity of the apical constriction after the sole use of electronic working length determination.

    Science.gov (United States)

    Wolgin, Michael; Grundmann, Markus J; Tchorz, Jörg P; Frank, Wilhelm; Kielbassa, Andrej M

    2017-09-01

    The present study investigated the accuracy of root canal preparation with regard to the integrity of the apical constriction (AC) using two different working length determination approaches: (1) the electronic method of working length determination (EWLD), and (2) the radiologic "gold standard" method (GS). Simulation models were constructed by arranging extracted human teeth by means of silicon bolstered gingiva masks, along with a conductive medium (alginate). Electronic working length determination (group 1; EWLD) and radiologic plus initial electronic working length determination for posterior comparability (group 2; GS) preceded manual root canal preparation of teeth in both groups. Master cones were inserted according to working lengths obtained from the group specific method. Subsequently, root apices (n=36) were longitudinally sectioned using a diamond-coated bur. The distance between the achieved apical endpoint of the endodontic preparation and the apical constriction (AC) was measured using digital photography. Then, distances between radiologically identified apical endpoints and AC (GS-AC) were compared with the corresponding distances EWLD-AC. Moreover, the postoperative status of the AC was examined with regard to both preparation approaches. Differences between distances GS-AC and EWLD-AC were not statistically significant (p >0.401) (Mann-Whitney-U). Among EWLD samples, 83% of the master cones exhibiting tugback at final insertion terminated close to the apical constriction (±0.5 mm), and no impairment of the minor diameter's integrity was observed. The sole use of EWLD allowed for a high accuracy of measurements and granted precise preparation of the apical regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. In vivo and qualitative studies investigating the translational potential of microneedles for use in the older population.

    Science.gov (United States)

    Quinn, Helen L; Hughes, Carmel M; Donnelly, Ryan F

    2017-05-15

    Microneedles (MNs) are a novel transdermal drug delivery platform, rapidly progressing from a substantive evidence base, towards commercialisation. As part of this transition, it is important to consider the future use of MNs by older people in order to ensure optimal therapeutic outcomes for this unique and increasing population group. This paper, therefore, considers the use of MNs by those aged over 65 years, investigating insertion parameters in ageing skin, alongside the feasibility and acceptability of the technology. Hydrogel-forming MN arrays were applied to seven subjects aged over 65 years, with breach of the stratum corneum confirmed using optical coherence tomography. Insertion depths recorded in each case were similar to a comparative group, aged 20-30 years. Skin recovery was, however, demonstrated to occur at a slower rate in the older subjects, as measured using transepidermal water loss. Qualitative methods, including focus groups and semi-structured interviews, were employed to collect the views and opinions of older people and community pharmacists respectively. The overall consensus was positive, with a number of benefits to MN-mediated drug delivery identified, such as reduced dosing frequency, improved adherence and an alternative delivery route where oral or injectable medication was precluded. Concerns centred on practical issues associated with age-related functional decline, including, for example, reduced dexterity and skin changes. The presentation of this work collectively provides the first convincing report of the importance of further translational research in this area to support future MN use in older people, ensuring an age-appropriate delivery platform.

  6. An investigation into the role of alcohol in self-harm in rural Sri Lanka: a protocol for a multimethod, qualitative study.

    Science.gov (United States)

    Sørensen, Jane Brandt; Rheinländer, Thilde; Sørensen, Birgitte Refslund; Pearson, Melissa; Agampodi, Thilini; Siribaddana, Sisira; Konradsen, Flemming

    2014-10-07

    Sri Lanka has one of the highest suicide and self-harm rates in the world and although alcohol has been found to be a risk factor for self-harm in Sri Lanka, we know little about the connection between the two. This paper comprises a protocol for a qualitative study investigating alcohol's role in self-harm in rural Sri Lanka at three levels: the individual, community and policy level. The analysis will bring new understanding of the link between alcohol and self-harm in Sri Lanka, drawing on structural, cultural and social concepts. It will equip researchers, health systems and policy makers with vital information for developing strategies to address alcohol-related problems as they relate to self-harm. To capture the complexity of the link between alcohol and self-harm in the Anuradhapura district in the North Central Province in Sri Lanka, qualitative methods will be utilised. Specifically, the data will consist of serial narrative life-story interviews with up to 20 individuals who have non-fatally self-harmed and where alcohol directly or indirectly was involved in the incidence as well as with their significant others; observations in communities and families; six focus group discussions with community members; and key-informant interviews with 15-25 stakeholders who have a stake in alcohol distribution, marketing, policies, prevention and treatment as they relate to self-harm. The study has received ethical approval from the Ethical Review Committee of the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. A sensitive data collection technique will be used and ethical issues will be considered throughout the study. The results will be disseminated in scientific peer-reviewed articles in collaboration with Sri Lankan and other international research partners. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Investigating within-day and longitudinal effects of maternal stress on children's physical activity, dietary intake, and body composition: Protocol for the MATCH study.

    Science.gov (United States)

    Dunton, Genevieve F; Liao, Yue; Dzubur, Eldin; Leventhal, Adam M; Huh, Jimi; Gruenewald, Tara; Margolin, Gayla; Koprowski, Carol; Tate, Eleanor; Intille, Stephen

    2015-07-01

    Parental stress is an understudied factor that may compromise parenting practices related to children's dietary intake, physical activity, and obesity. However, studies examining these associations have been subject to methodological limitations, including cross-sectional designs, retrospective measures, a lack of stress biomarkers, and the tendency to overlook momentary etiologic processes occurring within each day. This paper describes the recruitment, data collection, and data analytic protocols for the MATCH (Mothers And Their Children's Health) study, a longitudinal investigation using novel real-time data capture strategies to examine within-day associations of maternal stress with children's physical activity and dietary intake, and how these effects contribute to children's obesity risk. In the MATCH study, 200 mothers and their 8 to 12 year-old children are participating in 6 semi-annual assessment waves across 3 years. At each wave, measures for mother-child dyads include: (a) real-time Ecological Momentary Assessment (EMA) of self-reported daily psychosocial stressors (e.g., work at a job, family demands), feeling stressed, perceived stress, parenting practices, dietary intake, and physical activity with time and location stamps; (b) diurnal salivary cortisol patterns, accelerometer-monitored physical activity, and 24-hour dietary recalls; (c) retrospective questionnaires of sociodemographic, cultural, family, and neighborhood covariates; and (d) height, weight, and waist circumference. Putative within-day and longitudinal effects of maternal stress on children's dietary intake, physical activity, and body composition will be tested through multilevel modeling and latent growth curve models, respectively. The results will inform interventions that help mothers reduce the negative effects of stress on weight-related parenting practices and children's obesity risk. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

    OpenAIRE

    Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

    2007-01-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via...

  9. Improving implementation of evidence-based practice in mental health service delivery: protocol for a cluster randomised quasi-experimental investigation of staff-focused values interventions.

    Science.gov (United States)

    Williams, Virginia; Oades, Lindsay G; Deane, Frank P; Crowe, Trevor P; Ciarrochi, Joseph; Andresen, Retta

    2013-07-02

    There is growing acceptance that optimal service provision for individuals with severe and recurrent mental illness requires a complementary focus on medical recovery (i.e., symptom management and general functioning) and personal recovery (i.e., having a 'life worth living'). Despite significant research attention and policy-level support, the translation of this vision of healthcare into changed workplace practice continues to elude. Over the past decade, evidence-based training interventions that seek to enhance the knowledge, attitudes, and skills of staff working in the mental health field have been implemented as a primary redress strategy. However, a large body of multi-disciplinary research indicates disappointing rates of training transfer. There is an absence of empirical research that investigates the importance of worker-motivation in the uptake of desired workplace change initiatives. 'Autonomy' is acknowledged as important to human effectiveness and as a correlate of workplace variables like productivity, and wellbeing. To our knowledge, there have been no studies that investigate purposeful and structured use of values-based interventions to facilitate increased autonomy as a means of promoting enhanced implementation of workplace change. This study involves 200 mental health workers across 22 worksites within five community-managed organisations in three Australian states. It involves cluster-randomisation of participants within organisation, by work site, to the experimental (values) condition, or the control (implementation). Both conditions receive two days of training focusing on an evidence-based framework of mental health service delivery. The experimental group receives a third day of values-focused intervention and 12 months of values-focused coaching. Well-validated self-report measures are used to explore variables related to values concordance, autonomy, and self-reported implementation success. Audits of work files and staff work samples

  10. The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo.

    Science.gov (United States)

    Zhou, Ning; Singh, Kamini; Mir, Maria C; Parker, Yvonne; Lindner, Daniel; Dreicer, Robert; Ecsedy, Jeffrey A; Zhang, Zhongfa; Teh, Bin T; Almasan, Alexandru; Hansel, Donna E

    2013-04-01

    Despite more than 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluated Aurora kinase A, identified as an upregulated candidate molecule in bladder cancer, as a potential therapeutic target. Gene expression in human bladder cancer samples was evaluated using RNA microarray and quantitative reverse transcriptase PCR. Effects of the Aurora kinase A inhibitor MLN8237 (Millennium) on cell dynamics in malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells were evaluated in vitro and in vivo in a mouse xenograft model. A set of 13 genes involved in the mitotic spindle checkpoint, including Aurora kinases A and B, were upregulated in human urothelial carcinoma compared with normal urothelium. The Aurora kinase A inhibitor MLN8237 induced cell-cycle arrest, aneuploidy, mitotic spindle failure, and apoptosis in the human bladder cancer cell lines T24 and UM-UC-3. MLN8237 also arrested tumor growth when administered orally over 4 weeks in a mouse bladder cancer xenograft model. Finally, in vitro sequential administration of MLN8237 with either paclitaxel or gemcitabine resulted in synergistic cytotoxic effects in T24 cells. Mitotic spindle checkpoint dysfunction is a common characteristic of human urothelial carcinoma and can be exploited with pharmacologic Aurora A inhibition. Given our demonstration of the ability of the Aurora A inhibitor MLN8237 to inhibit growth of bladder cancer in vitro and in vivo, we conclude that Aurora kinase inhibitors warrant further therapeutic investigation in bladder cancer. ©2013 AACR.

  11. The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell cycle progression in malignant bladder cancer cells in vitro and in vivo

    Science.gov (United States)

    Zhou, Ning; Singh, Kamini; Mir, Maria C.; Parker, Yvonne; Lindner, Daniel; Dreicer, Robert; Ecsedy, Jeffrey A; Zhang, Zhongfa; Teh, Bin T.; Almasan, Alexandru; Hansel, Donna E.

    2013-01-01

    PURPOSE Despite over 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluated Aurora kinase A, identified as an upregulated candidate molecule in bladder cancer, as a potential therapeutic target. EXPERIMENTAL DESIGN Gene expression in human bladder cancer samples was evaluated using RNA microarray and quantitative reverse-transcriptase PCR. Effects of the Aurora kinase A inhibitor MLN8237 (Millennium) on cell dynamics in malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells were evaluated in vitro and in vivo in a mouse xenograft model. RESULTS A set of 13 genes involved in the mitotic spindle checkpoint, including Aurora kinases A and B, were upregulated in human urothelial carcinoma compared to normal urothelium. The Aurora kinase A inhibitor MLN8237 induced cell cycle arrest, aneuploidy, mitotic spindle failure, and apoptosis in the human bladder cancer cell lines T24 and UM-UC-3. MLN8237 also arrested tumor growth when administered orally over 4 weeks in a mouse bladder cancer xenograft model. Finally, in vitro sequential administration of MLN8237 with either paclitaxel or gemcitabine resulted in synergistic cytotoxic effects in T24 cells. CONCLUSIONS Mitotic spindle checkpoint dysfunction is a common characteristic of human urothelial carcinoma, and can be exploited with pharmacologic Aurora A inhibition. Given our demonstration of the ability of the Aurora A inhibitor MLN8237 to inhibit growth of bladder cancer in vitro and in vivo, we conclude that Aurora kinase inhibitors warrant further therapeutic investigation in bladder cancer. PMID:23403633

  12. Peer Observations among Faculty in a College of Education: Investigating the Summative and Formative Uses of the Reformed Teaching Observation Protocol (RTOP)

    Science.gov (United States)

    Amrein-Beardsley, Audrey; Osborn Popp, Sharon E.

    2012-01-01

    Teacher educators piloted the use of the Reformed Teaching Observation Protocol (RTOP), a peer observation instrument associated with increases in learning in science and mathematics teacher education courses. Faculty participants received a series of trainings in RTOP use and rated each other's teaching during multiple peer observations. The…

  13. A study protocol of a randomised controlled trial to investigate if a community based strength training programme improves work task performance in young adults with Down syndrome

    Directory of Open Access Journals (Sweden)

    Taylor Nicholas F

    2010-03-01

    Full Text Available Abstract Background Muscle strength is important for young people with Down syndrome as they make the transition to adulthood, because their workplace activities typically emphasise physical rather than cognitive skills. Muscle strength is reduced up to 50% in people with Down syndrome compared to their peers without disability. Progressive resistance training improves muscle strength and endurance in people with Down syndrome. However, there is no evidence on whether it has an effect on work task performance or physical activity levels. The aim of this study is to investigate if a student-led community-based progressive resistance training programme can improve these outcomes in adolescents and young adults with Down syndrome. Methods A randomised controlled trial will compare progressive resistance training with a control group undertaking a social programme. Seventy adolescents and young adults with Down syndrome aged 14-22 years and mild to moderate intellectual disability will be randomly allocated to the intervention or control group using a concealed method. The intervention group will complete a 10-week, twice a week, student-led progressive resistance training programme at a local community gymnasium. The student mentors will be undergraduate physiotherapy students. The control group will complete an arts/social programme with a student mentor once a week for 90 minutes also for 10 weeks to control for the social aspect of the intervention. Work task performance (box stacking, pail carry, muscle strength (1 repetition maximum for chest and leg press and physical activity (frequency, duration, intensity over 7-days will be assessed at baseline (Week 0, following the intervention (Week 11, and at 3 months post intervention (Week 24 by an assessor blind to group allocation. Data will be analysed using ANCOVA with baseline measures as covariates. Discussion This paper outlines the study protocol for a randomised controlled trial on the

  14. Investigating fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO): a scoping review protocol.

    Science.gov (United States)

    Mostafavi-Pour-Manshadi, Seyed-Mohammad-Yousof; Naderi, Nafiseh; Barrecheguren, Miriam; Dehghan, Abolfazl; Bourbeau, Jean

    2017-12-21

    During the last decade, many articles have been published, including reviews on fractional exhaled nitric oxide (FeNO) use and utility in clinical practice and for monitoring and identifying eosinophilic airway inflammation, especially in asthma, and evaluating corticosteroid responsiveness. However, the exact role of FeNO in patients with chronic obstructive pulmonary disease (COPD) and its ability to distinguish patients with COPD and those having concomitant asthma, that is, asthma-COPD overlap (ACO) is still unclear and needs to be defined. Due to the broad topics of FeNO in chronic airway disease, we undertook a scoping review. The present article describes the protocol of a scoping review of peer-reviewed published literature specific to FeNO in COPD/ACO over the last decade. We used Joanna Briggs Institute Reviewers' Manual scoping review methodology as well as Levac et al 's and Arksey et al 's framework as guides. We searched a variety of databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and BioSciences Information Service (BIOSIS) on 29 June 2016. Additional studies will be recognised by exploring the reference list of identified eligible studies. Screening of eligible studies will be independently performed by two reviewers and any disagreement will be solved by the third reviewer. We will analyse the gathered data from article bibliographies and abstracts. To investigate the body of published studies regarding the role of FeNO in patients with COPD and its usefulness in the clinical setting, a scoping review can be used as a modern and pioneer model, which does not need ethics approval. By this review, new insights for conducting new research specific to FeNO in COPD/ACO population will emerge. The results of this study will be reported in the scientific meetings and conferences, which aim to provide information to the clinicians, primary care providers and basic

  15. Investigating the burden of antibiotic resistance in ethnic minority groups in high-income countries: protocol for a systematic review and meta-analysis.

    Science.gov (United States)

    Lishman, Hannah; Aylin, Paul; Alividza, Vivian; Castro-Sanchez, Enrique; Chatterjee, Anuja; Mariano, Victor; Johnson, Alan P; Jeraj, Samir; Costelloe, Céire

    2017-12-11

    Antibiotic resistance (ABR) is an urgent problem globally, with overuse and misuse of antibiotics being one of the main drivers of antibiotic-resistant infections. There is increasing evidence that the burden of community-acquired infections such as urinary tract infections and bloodstream infections (both susceptible and resistant) may differ by ethnicity, although the reasons behind this relationship are not well defined. It has been demonstrated that socioeconomic status and ethnicity are often highly correlated with each other; however, it is not yet known whether accounting for deprivation completely explains any discrepancy seen in infection risk. There have currently been no systematic reviews summarising the evidence for the relationship between ethnicity and antibiotic resistance or prescribing. This protocol will outline how we will conduct this systematic literature review and meta-analysis investigating whether there is an association between patient ethnicity and (1) risk of antibiotic-resistant infections or (2) levels of antibiotic prescribing in high-income countries. We will search PubMed/MEDLINE, EMBASE, Global Health, Scopus and CINAHL using MESH terms where applicable. Two reviewers will conduct title/abstract screening, data extraction and quality assessment independently. The Critical Appraisal Skills Programme (CASP) checklist will be used for cohort and case-control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials, if they are included. Meta-analyses will be performed by calculating the minority ethnic group to majority ethnic group odds ratios or risk ratios for each study and presenting an overall pooled odds ratio for the two outcomes. The Grading of Recommendations, Assessments, Development and Evaluation (GRADE) approach will be used to assess the overall quality of the body of evidence. In this systematic review and meta-analysis, we will aim to collate the available evidence of

  16. Proper protocol

    NARCIS (Netherlands)

    F. Arbab (Farhad)

    2016-01-01

    textabstractTreating interaction as an explicit first-class concept, complete with its own composition operators, leads to a model of concurrency that allows direct specification and manipulation of protocols as proper mathematical objects. Reo [2,5,6,8] serves as a premier example of such an

  17. Investigation of phytochemical contents, in vitro antioxidant and antibacterial behavior and in vivo anti-inflammatory potential of Ecballium elaterium methanol fruits extract

    Directory of Open Access Journals (Sweden)

    Samir FELHI

    Full Text Available Abstract Ecballium elaterium species are mostly used as therapeutic agents and food ingredient. The current work was designed to investigate phytochemical contents, antioxidant, antibacterial, and anti-inflammatory properties of methanol fruits extract of Ecballium elaterium. Good antioxidant activity was observed with IC50 values of 156 ± 4 and 377 ± 6 μg/mL for DPPH and ABTS, respectively, and EC50 of 126 ± 4 µg/mL for FRAP assays, which is related with their richness in total phenolic, flavonoid and condensed tannins contents. The results of antibacterial activity showed the effectiveness of methanol extract against Bacillus cereus with value of inhibition zone diameter of 15 ± 0 mm and a MIC and MBC values of 6 ± 0 and 12 ± 0 mg/mL, respectively. The in vivo anti-inflammatory effects have been also studied by carrageenan induced rat paw edema assay and the results revealed that a dose of 75 mg/kg induced a significant inhibition of 66.4% at 2 h. FT-IR spectral data justified the presence of biological functional groups such as ─OH, C─H, C─O, C─C and C=O. These results highlighted the potential using of Ecballium elaterium fruits extract as natural antimicrobial, antioxidant and anti-inflammatory agents for food applications and for the pharmaceutical industry.

  18. A field investigation of a modified intravaginal progesterone releasing device and oestradiol benzoate based ovulation synchronisation protocol designed for fixed-time artificial insemination of Brahman heifers.

    Science.gov (United States)

    Edwards, S A A; Boe-Hansen, G B; Satake, N; Chandra, K; McGowan, M R

    2015-09-01

    Pregnancy rates (PR) to fixed-time AI (FTAI) in Brahman heifers were compared after treatment with a traditional oestradiol-based protocol (OPO-8) or a modified protocol (OPO-6) where the duration of intravaginal progesterone releasing device (IPRD) was reduced from 8 to 6 days, and the interval from IPRD removal to oestradiol benzoate (ODB) was increased from 24 to 36 h. Rising 2 yo heifers on Farm A: (n = 238 and n = 215; two consecutive days AI); B (n = 271); and C (n = 393) were allocated to OPO-8 or OPO-6. An IPRD was inserted and 1mg ODB i.m. on Day 0 for OPO-8 heifers and Day 2 for OPO-6 heifers. On Day 8, the IPRD was removed and 500 μg cloprostenol i.m. At 24h, for OPO-8 heifers, and 36 h, for OPO-6 heifers, post IPRD removal all heifers received 1mg ODB i.m. FTAI was conducted at 54 and 72 h post IPRD removal for OPO-8 and OPO-6 heifers. At Farm A, OPO-6 heifers, AI on the second day, the PR was 52.4% to FTAI (P = 0.024) compared to 36.8% for OPO-8 heifers. However, no differences were found between OPO-8 and OPO-6 protocols at Farm A (first day of AI) (39.9 vs. 35.7%), or Farms B (26.2 vs. 35.4%) and C (43.2% vs. 40.3%). Presence of a corpus luteum at IPRD insertion affected PR to FTAI (43.9% vs. 28.8%; P OPO-6 may be a viable alternative to the OPO-8 protocol for FTAI in B. indicus heifers. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Investigation of lithium distribution in the rat brain ex vivo using lithium-7 magnetic resonance spectroscopy and imaging at 17.2 T.

    Science.gov (United States)

    Stout, Jacques; Hanak, Anne-Sophie; Chevillard, Lucie; Djemaï, Boucif; Risède, Patricia; Giacomini, Eric; Poupon, Joël; Barrière, David André; Bellivier, Frank; Mégarbane, Bruno; Boumezbeur, Fawzi

    2017-11-01

    Lithium is the first-line mood stabilizer for the treatment of patients with bipolar disorder. However, its mechanisms of action and transport across the blood-brain barrier remain poorly understood. The contribution of lithium-7 magnetic resonance imaging (7 Li MRI) to investigate brain lithium distribution remains limited because of the modest sensitivity of the lithium nucleus and the expected low brain concentrations in humans and animal models. Therefore, we decided to image lithium distribution in the rat brain ex vivo using a turbo-spin-echo imaging sequence at 17.2 T. The estimation of lithium concentrations was performed using a phantom replacement approach accounting for B1 inhomogeneities and differential T1 and T2 weighting. Our MRI-derived lithium concentrations were validated by comparison with inductively coupled plasma-mass spectrometry (ICP-MS) measurements ([Li]MRI  = 1.18[Li]MS , R = 0.95). Overall, a sensitivity of 0.03 mmol/L was achieved for a spatial resolution of 16 μL. Lithium distribution was uneven throughout the brain (normalized lithium content ranged from 0.4 to 1.4) and was mostly symmetrical, with consistently lower concentrations in the metencephalon (cerebellum and brainstem) and higher concentrations in the cortex. Interestingly, low lithium concentrations were also observed close to the lateral ventricles. The average brain-to-plasma lithium ratio was 0.34 ± 0.04, ranging from 0.29 to 0.39. Brain lithium concentrations were reasonably correlated with plasma lithium concentrations, with Pearson correlation factors ranging from 0.63 to 0.90. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    Science.gov (United States)

    Avcıbaşı, Uğur; Avcıbaşı, Nesibe; Akalın, Hilmi Arkut; Ediz, Melis; Demiroğlu, Hasan; Gümüşer, Fikriye Gül; Özçalışkan, Emir; Türkcan, Ceren; Uygun, Deniz Aktaş; Akgöl, Sinan

    2013-10-01

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe3O4 particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, 131I. Thin-layer radiochromatography experiments demonstrated that 131I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 ± 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with 131I [131I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with 131I is a compound which has a significant potential for being used as an anti-cancer agent. Certain results can only be obtained whether this

  1. A Survey on Investigating the Need for Intelligent Power-Aware Load Balanced Routing Protocols for Handling Critical Links in MANETs

    Directory of Open Access Journals (Sweden)

    B. Sivakumar

    2014-01-01

    Full Text Available In mobile ad hoc networks connectivity is always an issue of concern. Due to dynamism in the behavior of mobile nodes, efficiency shall be achieved only with the assumption of good network infrastructure. Presence of critical links results in deterioration which should be detected in advance to retain the prevailing communication setup. This paper discusses a short survey on the specialized algorithms and protocols related to energy efficient load balancing for critical link detection in the recent literature. This paper also suggests a machine learning based hybrid power-aware approach for handling critical nodes via load balancing.

  2. Comparison of In-Vitro and Ex-Vivo Wound Healing Assays for the Investigation of Diabetic Wound Healing and Demonstration of a Beneficial Effect of a Triterpene Extract.

    Directory of Open Access Journals (Sweden)

    Christopher Ueck

    Full Text Available Diabetes mellitus is a frequent cause for chronic, difficult-to-treat wounds. New therapies for diabetic wounds are urgently needed and in-vitro or ex-vivo test systems are essential for the initial identification of new active molecules. The aim of this study is to compare in-vitro and ex-vivo test systems for their usability for early drug screening and to investigate the efficacy of a birch bark triterpene extract (TE that has been proven ex-vivo and clinically to accelerate non-diabetic wound healing (WH, in a diabetic context. We investigated in-vitro models for diabetic WH, i.e. scratch assays with human keratinocytes from diabetic donors or cultured under hyperglycaemic conditions and a newly developed porcine ex-vivo hyperglycaemic WH model for their potential to mimic delayed diabetic WH and for the influence of TE in these test systems. We show that keratinocytes from diabetic donors often fail to exhibit significantly delayed WH. For cells under hyperglycaemic conditions significant decrease is observed but is influenced by choice of medium and presence of supplements. Also, donor age plays a role. Interestingly, hyperglycaemic effects are mainly hyperosmolaric effects in scratch assays. Ex-vivo models under hyperglycaemic conditions show a clear and substantial decrease of WH, and here both glucose and hyperosmolarity effects are involved. Finally, we provide evidence that TE is also beneficial for ex-vivo hyperglycaemic WH, resulting in significantly increased length of regenerated epidermis to 188±16% and 183±11% (SEM; p<0.05 compared to controls when using two different TE formulations. In conclusion, our results suggest that microenvironmental influences are important in WH test systems and that therefore the more complex hyperglycaemic ex-vivo model is more suitable for early drug screening. Limitations of the in-vitro and ex-vivo models are discussed. Furthermore our data recommend TE as a promising candidate for in-vivo

  3. Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

    Science.gov (United States)

    Wang, Mengshu; Zhang, Yong; Feng, Jiao; Gu, Tiejun; Dong, Qingguang; Yang, Xu; Sun, Yanan; Wu, Yongge; Chen, Yan; Kong, Wei

    2013-01-01

    Background Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results Nanoparticles were prepared using a modified water–oil–water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9- and 16.5-fold, respectively

  4. Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Ugur, E-mail: uguravcibasi@yahoo.com [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Nesibe [Ege University, Ege Higher Vocational School (Turkey); Akal Latin-Small-Letter-Dotless-I n, Hilmi Arkut; Ediz, Melis; Demiroglu, Hasan [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Guemueser, Fikriye Guel [Celal Bayar University, Department of Nuclear Medicine, Faculty of Medicine (Turkey); Oezcal Latin-Small-Letter-Dotless-I skan, Emir; Tuerkcan, Ceren [Ege University, Department of Biochemistry, Faculty of Science (Turkey); Uygun, Deniz Aktas [Adnan Menderes University, Department of Chemistry, Faculty of Arts and Science (Turkey); Akgoel, Sinan [Ege University, Department of Biochemistry, Faculty of Science (Turkey)

    2013-10-15

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe{sub 3}O{sub 4} particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, {sup 131}I. Thin-layer radiochromatography experiments demonstrated that {sup 131}I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 {+-} 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with {sup 131}I [{sup 131}I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with {sup 131}I is a compound which has a significant potential for being used as an anti-cancer agent. Certain

  5. 177Lu-labeled HPMA copolymers utilizing cathepsin B and S cleavable linkers: synthesis, characterization and preliminary in vivo investigation in a pancreatic cancer model.

    Science.gov (United States)

    Ogbomo, Sunny M; Shi, Wen; Wagh, Nilesh K; Zhou, Zhengyuan; Brusnahan, Susan K; Garrison, Jered C

    2013-07-01

    A major barrier to the advancement of therapeutic nanomedicines has been the non-target toxicity caused by the accumulation of the drug delivery systems in organs associated with the reticuloendothelial system, particularly the liver and spleen. Herein, we report the development of peptide based metabolically active linkers (MALs) that are enzymatically cleaved by cysteine cathepsin B and S, two proteases highly expressed in the liver and spleen. The overall goal of this approach is to utilize the MALs to lower the non-target retention and toxicity of radiolabeled drug delivery systems, thus resulting in higher diagnostic and radiotherapeutic efficacy. In this study three MALs (MAL0, MAL1 and MAL2) were investigated. MAL1 and MAL2 are composed of known substrates of cathepsin B and S, respectively, while MAL0 is a non-cleavable control. Both MAL1 and MAL2 were shown to undergo enzymatic cleavage with the appropriate cathepsin protease. Subsequent to conjugation to the HPMA copolymer and radiolabeling with (177)Lu, the peptide-polymer conjugates were renamed (177)Lu-metabolically active copolymers ((177)Lu-MACs) with the corresponding designations: (177)Lu-MAC0, (177)Lu-MAC1 and (177)Lu-MAC2. In vivo evaluation of the (177)Lu-MACs was performed in an HPAC human pancreatic cancer xenograft mouse model. (177)Lu-MAC1 and (177)Lu-MAC2 demonstrated 3.1 and 2.1 fold lower liver retention, respectively, compared to control ((177)Lu-MAC0) at 72h post-injection. With regard to spleen retention, (177)Lu-MAC1 and (177)Lu-MAC2 each exhibited a nearly fourfold lower retention, relative to control, at the 72h time point. However, the tumor accumulation of the (177)Lu-MAC0 was two to three times greater than (177)Lu-MAC1 and (177)Lu-MAC2 at the same time point. The MAL approach demonstrated the capability of substantially reducing the non-target retention of the (177)Lu-labeled HPMA copolymers. While further studies are needed to optimize the pharmacokinetics of the (177)Lu

  6. Species Extrapolation of Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models to Investigate the Developmental Toxicology of Ethanol Using In vitro to In vivo (IVIVE) Methods

    Science.gov (United States)

    To provide useful alternatives to in vivo animal studies, in vitro assays for dose-response assessments of xenobiotic chemicals must use concentrations in media and target tissues that are within biologically-plausible limits. Determining these concentrations is a complex matter,...

  7. Setting up and using the autopatcher for automated intracellular neural recording in vivo

    Science.gov (United States)

    Kodandaramaiah, Suhasa B.; Holst, Gregory L.; Wickersham, Ian R.; Singer, Annabelle C.; Franzesi, Giovanni Talei; McKinnon, Michael L.; Forest, Craig R.; Boyden, Edward S.

    2016-01-01

    Whole cell patch clamping in vivo is an important neuroscience technique that uniquely provides access to both supra-threshold spiking and sub-threshold synaptic events of single neurons in the brain. This article describes how to set up and use the autopatcher, a robot for automatically obtaining high yield and high quality whole cell patch clamp recordings in vivo. Following this protocol, a functional experimental rig for automated whole cell patch clamping can be set up in one week. High quality surgical preparation of mice takes approximately 1 hour, and each autopatching experiment can be carried out over periods lasting several hours. Autopatching should enable in vivo intracellular investigations to be accessible by a significant number of neuroscience labs, and enable labs already doing in vivo patch clamp to scale up their efforts by reducing training time for new lab members and increasing experimental durations by handling mentally intensive tasks automatically. PMID:26938115

  8. Investigating the nature of interprofessional collaboration in primary care across the Western Health Region of Brasília, Brazil: A study protocol.

    Science.gov (United States)

    Pinho, Diana; Parreira, Clelia; Queiroz, Elizabeth; Abbad, Gardênia; Reeves, Scott

    2018-03-01

    Primary care can provide a supportive context for the development of interprofessional collaborative practice owing to its nature and dynamics. In Brazil, a number of practice changes have already occurred to primary care, notably the implementation of the Family Health Strategy which promoted interprofessional collaboration (IPC). In Brasilia, a new arrangement was implemented in 2016 that focused on an expansion of primary healthcare. However, it is not clear how these reforms will affect the nature of IPC or the delivery of patient care. The article presents a study protocol which describes a study that aims to explore the nature of IPC in the context of primary care in the Western Health Region of Brasilia. A sequential mixed methods design will be used to gather both quantitative and qualitative data. Initially, we will translate, cross-culturally adapt, and validate an IPC scale for a survey of primary care teams. We will then undertake a series of focus groups with a purposeful sample of team members to explore the results from the survey. Quantitative data will be analysed with descriptive and multivariate statistics. A content analysis will be undertaken with the focus group data. We expect that the results will illuminate a range of elements linked to IPC in primary care as well as identify areas for improving IPC skills, patient safety, quality of care, and healthcare outcomes in this clinical context.

  9. Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

    Directory of Open Access Journals (Sweden)

    Crossman David C

    2010-10-01

    Full Text Available Abstract Background Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design Sixty patients with stable angina will be recruited and randomised 1:1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training. Trial Registration Clinicaltrials.gov identifier: NCT01147952

  10. Investigation of microstructure, mechanical properties and cellular viability of poly(L-lactic acid) tissue engineering scaffolds prepared by different thermally induced phase separation protocols.

    Science.gov (United States)

    Molladavoodi, Sara; Gorbet, Maud; Medley, John; Kwon, Hyock Ju

    2013-01-01

    Two thermally induced phase separation (TIPS) methods have been used to fabricate biodegradable poly(L-lactic acid) (PLLA) tissue engineering scaffolds each with fibrous (F-TIPS) and porous (P-TIPS) microstructures. Three levels of PLLA concentration (3, 5 and 7 wt%) were employed in each fabrication method and both wet and dry specimens were studied. Simple compression testing revealed that an elastic-plastic representation of the mechanical behavior was possible for all specimens. Both elastic and plastic moduli were higher for the P-TIPS, for higher polymer concentration, and might be somewhat higher for dry as opposed to wet specimens. For F-TIPS specimens, permanent deformation occurred successively during cyclic deformation but a "memory effect" simplified the behavior. Although F-TIPS microstructure better resembled the natural extracellular matrix, human osteosarcoma fibroblast cells showed more consistent viability in the P-TIPS scaffolds under our unloaded test protocols. Biodegradation in cell culture medium resulted in a decreased elastic moduli for F-TIPS specimens. Information presented regarding the microstructure, mechanical properties and cell viability of these PLLA scaffolds that should help reduce the number of iterations involved in developing tissue engineering products. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Investigation of complexes with bone affinity using the In vivo generator system {sup 166} Dy/{sup 166} Ho; Investigacion de complejos con afinidad osea utilizando el Sistema de Generador in vivo {sup 166} Dy/{sup 166} Ho

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M

    2006-07-01

    The importance of this original research lies in the fact that it has proven that the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system is a stable complex that can be used as a therapeutic radiopharmaceutical. Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. Bone-seeking radiopharmaceuticals such as {sup 166}Ho-DOTMP or {sup 153}Sm-DTMP, have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other hematological malignancies or have shown excellent results in palliative bone metastasis pain therapy, respectively. As lanthanides have similar chemical characteristics the phosphonate with bone affinity (EDTMP) labeled with Dy/Ho can be used for marrow ablation while causing minimal irradiation to normal organs. This in vivo generator system has not been previously reported. The aim of this research was to label EDTMP (ethylene diamine tetramethylene phosphonate) with {sup 166}Dy/{sup 166}Ho; to evaluate the in vitro and in vivo stability of both {sup 166}Dy-EDTMP and {sup 166}Ho-EDTMP complexes when the daughter {sup 166}Ho is formed as a dysprosium decay product; to determine the bone marrow cytotoxic and genotoxic effect in mice and to evaluate, by histopathology, the myeloablative potential of the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system. {sup 166}Dy was obtained by neutron irradiation of enriched {sup 164}Dy{sub 2}O{sub 3} in a TRIGA Mark III reactor. Labeling was carried out in an aqueous phosphate medium at pH 8.0 by addition of {sup 166}DyCl{sub 3} to EDTMP at a molar ratio 1:1.75, with >99 % radiochemical purity, as determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). In vitro studies demonstrated that {sup 166}Dy/{sup 166}Ho-EDTMP is unstable after dilution in saline but stable in human serum with no translocation of the daughter nucleus

  12. An Ultrasound Image-Based Dynamic Fusion Modeling Method for Predicting the Quantitative Impact of In Vivo Liver Motion on Intraoperative HIFU Therapies: Investigations in a Porcine Model.

    Directory of Open Access Journals (Sweden)

    W Apoutou N'Djin

    Full Text Available Organ motion is a key component in the treatment of abdominal tumors by High Intensity Focused Ultrasound (HIFU, since it may influence the safety, efficacy and treatment time. Here we report the development in a porcine model of an Ultrasound (US image-based dynamic fusion modeling method for predicting the effect of in vivo motion on intraoperative HIFU treatments performed in the liver in conjunction with surgery. A speckle tracking method was used on US images to quantify in vivo liver motions occurring intraoperatively during breathing and apnea. A fusion modeling of HIFU treatments was implemented by merging dynamic in vivo motion data in a numerical modeling of HIFU treatments. Two HIFU strategies were studied: a spherical focusing delivering 49 juxtapositions of 5-second HIFU exposures and a toroidal focusing using 1 single 40-second HIFU exposure. Liver motions during breathing were spatially homogenous and could be approximated to a rigid motion mainly encountered in the cranial-caudal direction (f = 0.20 Hz, magnitude > 13 mm. Elastic liver motions due to cardiovascular activity, although negligible, were detectable near millimeter-wide sus-hepatic veins (f = 0.96 Hz, magnitude 75%. Fusion modeling predictions were preliminarily validated in vivo and showed the potential of using a long-duration toroidal HIFU exposure to accelerate the ablation process during breathing (from 0.5 to 6 cm3 · min(-1. To improve HIFU treatment control, dynamic fusion modeling may be interesting for assessing numerically focusing strategies and motion compensation techniques in more realistic conditions.

  13. An Ultrasound Image-Based Dynamic Fusion Modeling Method for Predicting the Quantitative Impact of In Vivo Liver Motion on Intraoperative HIFU Therapies: Investigations in a Porcine Model

    Science.gov (United States)

    N'Djin, W. Apoutou; Chapelon, Jean-Yves; Melodelima, David

    2015-01-01

    Organ motion is a key component in the treatment of abdominal tumors by High Intensity Focused Ultrasound (HIFU), since it may influence the safety, efficacy and treatment time. Here we report the development in a porcine model of an Ultrasound (US) image-based dynamic fusion modeling method for predicting the effect of in vivo motion on intraoperative HIFU treatments performed in the liver in conjunction with surgery. A speckle tracking method was used on US images to quantify in vivo liver motions occurring intraoperatively during breathing and apnea. A fusion modeling of HIFU treatments was implemented by merging dynamic in vivo motion data in a numerical modeling of HIFU treatments. Two HIFU strategies were studied: a spherical focusing delivering 49 juxtapositions of 5-second HIFU exposures and a toroidal focusing using 1 single 40-second HIFU exposure. Liver motions during breathing were spatially homogenous and could be approximated to a rigid motion mainly encountered in the cranial-caudal direction (f = 0.20Hz, magnitude >13mm). Elastic liver motions due to cardiovascular activity, although negligible, were detectable near millimeter-wide sus-hepatic veins (f = 0.96Hz, magnitude HIFU exposure in stationary tissues (Dice Similarity Coefficient: DSCHIFU ablations during respiration, either by juxtaposing “cigar-shaped” lesions with spherical HIFU exposures, or by generating one large single lesion with toroidal HIFU exposures (DSC>75%). Fusion modeling predictions were preliminarily validated in vivo and showed the potential of using a long-duration toroidal HIFU exposure to accelerate the ablation process during breathing (from 0.5 to 6 cm3·min-1). To improve HIFU treatment control, dynamic fusion modeling may be interesting for assessing numerically focusing strategies and motion compensation techniques in more realistic conditions. PMID:26398366

  14. A Novel In Vivo Joint Loading System to Investigate the Effect of Daily Mechanical Load on a Healing Anterior Cruciate Ligament Reconstruction

    OpenAIRE

    Stasiak, Mark; Imhauser, Carl; Packer, Jonathan; Bedi, Asheesh; Brophy, Robert; Kovacevic, David; Jackson, Kent; Deng, Xiang-Hua; Rodeo, Scott; Torzilli, Peter

    2010-01-01

    We designed and validated a novel knee joint fixation/distraction system to study tendon–to-bone healing in an in vivo rat model of anterior cruciate ligament (ACL) reconstruction. The system uses an external fixator to apply a cyclic distraction of the knee joint while monitoring the resultant force developed across the joint, thus providing a temporal indication of structural changes during the healing process of the bone-tendon-bone reconstruction. The validation was performed using an opt...

  15. In vivo metabolic investigation of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry in combination with online hydrogen/deuterium exchange experiments.

    Science.gov (United States)

    Raju, B; Ramesh, M; Borkar, Roshan M; Srinivas, R; Padiya, Raju; Banerjee, Sanjay K

    2012-08-30

    Tuberculosis is a leading cause of death from an infectious disease and moxifloxacin is an effective drug as compared to other fluoroquinolones. To date only two metabolites of the drug are known. Therefore, the present study on characterization of hitherto unknown in vivo metabolites of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) is undertaken. In vivo metabolites of moxifloxacin have been identified and characterized by using LC/ESI-MS/MS in combination with an online hydrogen/deuterium (H/D) exchange technique. To identify in vivo metabolites, blood, urine and faeces samples were collected after oral administration of moxifloxacin to Sprague-Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation, liquid-liquid extraction followed by solid-phase extraction and LC/MS/MS analysis. A total of nine phase I and ten phase II metabolites of moxifloxacin have been identified in urine samples including N-sulphated, glucuronide and hydroxylated metabolites which are also observed in plasma samples. In faeces samples, only the N-sulphated metabolite is observed. The structures of metabolites have been elucidated based on fragmentation patterns, accurate mass measurements and online H/D exchange LC/MS/MS experiments. Online H/D exchange experiments are used to support the identification and structural characterization of drug metabolites. A total of 19 in vivo metabolites of moxifloxacin have been characterized using LC/ESI-MS/MS in combination with accurate mass measurements and online H/D exchange experiments. The main phase I metabolites of moxifloxacin are hydroxylated, decarbonylated, desmethylated and desmethylhydroxylated metabolites which undergo subsequent phase II glucuronidation pathways. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Overcoming language barriers in healthcare: A protocol for investigating safe and effective communication when patients or clinicians use a second language.

    Science.gov (United States)

    Meuter, Renata F I; Gallois, Cindy; Segalowitz, Norman S; Ryder, Andrew G; Hocking, Julia

    2015-09-10

    Miscommunication in the healthcare sector can be life-threatening. The rising number of migrant patients and foreign-trained staff means that communication errors between a healthcare practitioner and patient when one or both are speaking a second language are increasingly likely. However, there is limited research that addresses this issue systematically. This protocol outlines a hospital-based study examining interactions between healthcare practitioners and their patients who either share or do not share a first language. Of particular interest are the nature and efficacy of communication in language-discordant conversations, and the degree to which risk is communicated. Our aim is to understand language barriers and miscommunication that may occur in healthcare settings between patients and healthcare practitioners, especially where at least one of the speakers is using a second (weaker) language. Eighty individual interactions between patients and practitioners who speak either English or Chinese (Mandarin or Cantonese) as their first language will be video recorded in a range of in- and out-patient departments at three hospitals in the Metro South area of Brisbane, Australia. All participants will complete a language background questionnaire. Patients will also complete a short survey rating the effectiveness of the interaction. Recordings will be transcribed and submitted to both quantitative and qualitative analyses to determine elements of the language used that might be particularly problematic and the extent to which language concordance and discordance impacts on the quality of the patient-practitioner consultation. Understanding the role that language plays in creating barriers to healthcare is critical for healthcare systems that are experiencing an increasing range of culturally and linguistically diverse populations both amongst patients and practitioners. The data resulting from this study will inform policy and practical solutions for

  17. Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-07-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped

  18. Imaging N-acyl homoserine lactone quorum sensing in vivo

    DEFF Research Database (Denmark)

    Christensen, Louise Dahl; van Gennip, Maria; Jakobsen, Tim Holm

    2011-01-01

    In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...... intratracheally with alginate beads containing both a P. aeruginosa strain together with the E. coli monitor strain can be investigated at different time points postinfection. Epifluorescent or confocal scanning laser microscopy (CSLM) is used to detect the GFP-expressing E. coli monitor strain in the lung...

  19. Protocol Coordinator II | Center for Cancer Research

    Science.gov (United States)

    Provides programmatic and logistical support for the operations of clinical research for Phase I and Phase II clinical trials Provides deployment of clinical support services for clinical research  Streamlines protocol development timeline Provides data and document collection and compilation for regulatory filing with the FDA and other regulatory authorities Provides technical review and report preparation Provides administrative coordination and general logistical support for regulatory activities Ensures the provision of training for investigators and associate staff to reinforce and enhance a GCP culture Provides quality assurance and quality control oversight Performs regulatory review of clinical protocols, informed consent and other clinical documents  Tracks and facilitates a portfolio of protocols through each process step (IRB, RAC, DSMB, Office of Protocol Services) Assists clinical investigators in preparing clinical research protocols, including writing and formatting protocol documents and consent forms Prepares protocol packages for review and ensures that protocol packages include all the required material and comply with CCR, NCI and NIH policies Collaborates with investigators to resolve any protocol/data issues Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI Institutional Review Board (IRB) and the clinical trial sponsor or the FDA Monitors the review process and maintains detailed, complete and accurate records for each protocol of the approvals at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events Attends and prepares minutes for the Branch Protocol Review Committees For protocols that are performed with other research centers: contacts coordinators at other centers to obtain review committee approvals at these centers,  maintains records of

  20. Dynamic protocol stack composition: protocol independent addressing

    OpenAIRE

    Michiels, Sam; Mahieu, Tom; Matthijs, Frank; Verbaeten, Pierre

    2001-01-01

    This paper presents a generic addressing framework (GAF) which enables the development of protocol stack independent applications. This framework has been developed in the context of dynamic protocol stack composition. Having a way to compose and build protocol stacks is not sufficient. The protocol layers a stack is composed of have an impact on the addressing used inside the stack. Since addresses are used by applications, the impact of modifying the stack dynamically is not automaticall...

  1. In vivo electroporation mediated gene delivery to the beating heart.

    Directory of Open Access Journals (Sweden)

    Erick L Ayuni

    Full Text Available Gene therapy may represent a promising alternative strategy for cardiac muscle regeneration. In vivo electroporation, a physical method of gene transfer, has recently evolved as an efficient method for gene transfer. In the current study, we investigated the efficiency and safety of a protocol involving in vivo electroporation for gene transfer to the beating heart. Adult male rats were anesthetised and the heart exposed through a left thoracotomy. Naked plasmid DNA was injected retrograde into the transiently occluded coronary sinus before the electric pulses were applied. Animals were sacrificed at specific time points and gene expression was detected. Results were compared to the group of animals where no electric pulses were applied. No post-procedure arrhythmia was observed. Left ventricular function was temporarily altered only in the group were high pulses were applied; CK-MB (Creatine kinase and TNT (Troponin T were also altered only in this group. Histology showed no signs of toxicity. Gene expression was highest at day one. Our results provide evidence that in vivo electroporation with an optimized protocol is a safe and effective tool for nonviral gene delivery to the beating heart. This method may be promising for clinical settings especially for perioperative gene delivery.

  2. Investigating an approach to identifying the biomechanical differences between intercostal cartilage in subjects with pectus excavatum and normals in vivo: preliminary assessment of normal subjects

    Science.gov (United States)

    Rechowicz, Krzysztof; McKenzie, Frederic; Yan, Zhenzhen; Bawab, Sebastian; Ringleb, Stacie

    2009-02-01

    The cause of pectus excavatum (PE) is unknown and little research has been done to assess the material properties of the PE costal cartilage. One source reported, after studying ex vivo various properties of the costal cartilage in cases of PE that the biomechanical stability of PE cartilage is decreased when compared to that of normals. Building on this idea, it would be beneficial to measure the biomechanical properties of the costal cartilages in vivo to further determine the differences between PE subjects and normals. An approach to doing this would be to use a modified FARO arm, which can read applied loads and resulting deflections. These values can be used to establish a finite element model of the chest area of a person with PE. So far, a validated technique for the registration between a CT based 3D model of the ribcage and a skin surface scan in case of PE has been addressed. On the basis of the data gathered from 10 subjects with normal chests using a robot arm, stylus and 3D laser scanner, we tried to evaluate the influence of inter-measurement respiration of a subject on results accuracy and the possibility of using the stylus for deflection measurement. In addition, we established the best strategy for taking measurements.

  3. Melatonin reduces hypoxic-ischaemic (HI) induced autophagy and apoptosis: An in vivo and in vitro investigation in experimental models of neonatal HI brain injury.

    Science.gov (United States)

    Hu, Yingying; Wang, Zhouguang; Liu, Yanlong; Pan, Shulin; Zhang, Hao; Fang, Mingchu; Jiang, Huai; Yin, Jiayu; Zou, Shuangshuang; Li, Zhenmao; Zhang, Hongyu; Lin, Zhenlang; Xiao, Jian

    2017-07-13

    Melatonin has neuroprotective effects in many diseases, including neonatal hypoxic-ischaemic (HI) brain injury. The purpose of this study was to evaluate the neuroprotective effects of melatonin both in vivo and in vitro and associated molecular mechanisms behind these effects. Postnatal day 7 male and female rat pups were subjected to unilateral HI, melatonin was injected intraperitoneally 1h before HI and an additional six doses were administered at 24h intervals. The pups were sacrificed at 24h and 7 d after HI. Pre-treatment with melatonin significantly reduced brain damage at 7 d after HI, with 15mg/kg melatonin achieving over 30% recovery in tissue loss compared to vehicle-treated animals. Autophagy and apoptotic cell death as indicated by autophagy associated proteins, cleaved caspase 3 and Tunel staining, was significantly inhibited after melatonin treatment in vivo as well as in PC12 cells. Melatonin treatment also significantly increased the GAP43 in the cortex. In conclusion, melatonin treatment reduced neonatal rat brain injury after HI, and this appeared to be related to inhibiting autophagy as well as reducing apoptotic cell death. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Protocol Coordinator III | Center for Cancer Research

    Science.gov (United States)

    Provides programmatic and logistical support for the operations of clinical research Provides deployment of clinical support services for clinical research Streamlines the protocol development timeline Provides data and documents collection and compilation for regulatory filing with the Food and Drug Administration (FDA) and other regulatory authorities Provides technical review and report preparation Provides administrative coordination and general logistical support for regulatory activities Ensures the provision of training for investigators and associate staff to reinforce and enhance a Good Clinical Practices (GCP) culture Oversees quality assurance and quality control, performs regulatory review of clinical protocols, informed consent and other clinical documents Tracks and facilitates a portfolio of protocols through each process step (Institutional Review Board [IRB], Regulatory Affairs Compliance [RAC], Data Safety Monitoring Board [DSMB], Office of Protocol Services) Assists clinical investigators in preparing clinical research protocols, including writing and formatting consent forms Prepares protocol packages for review and ensures that protocol packages include all required material and complies with CCR, NCI and NIH policies Collaborates with investigators to resolve any protocol/data issues Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI IRB, and the clinical trial sponsor or the FDA Monitors the review process and maintains detailed, complete and accurate approval records for each protocol at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events Attends and prepares minutes for the Branch Protocol Review Committees Contacts coordinators at other centers for protocols that are performed there to obtain review committee approvals at those centers

  5. HEPBURN - investigating the efficacy and safety of nebulized heparin versus placebo in burn patients with inhalation trauma: study protocol for a multi-center randomized controlled trial.

    Science.gov (United States)

    Glas, Gerie J; Muller, Johannes; Binnekade, Jan M; Cleffken, Berry; Colpaert, Kirsten; Dixon, Barry; Juffermans, Nicole P; Knape, Paul; Levi, Marcel M; Loef, Bert G; Mackie, David P; Malbrain, Manu; Schultz, Marcus J; van der Sluijs, Koenraad F

    2014-03-25

    Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma. The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours. As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma. NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013.Recruiting. Randomisation commenced on 1 January 2014.

  6. Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib - findings from an investigator initiated phase 2 study

    DEFF Research Database (Denmark)

    Niemann, Carsten U; Herman, Sarah E M; Maric, Irina

    2016-01-01

    of tumor cells from the microenvironment. While the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment. EXPERIMENTAL DESIGN: Patients received single...... the chemoattraction of CLL cells. CONCLUSIONS: In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the anti-tumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL.......PURPOSE: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress...

  7. Investigation of skin permeation, ex vivo inhibition of venom-induced tissue destruction, and wound healing of African plants used against snakebites

    DEFF Research Database (Denmark)

    Schmidt, Marianne Molander; Stærk, Dan; Nielsen, Hanne Mørck

    2015-01-01

    . Materials and methods Extracts which had previously shown in vitro inhibitory activity against necrosis enzymes, were tested in an ex vivo air–liquid-interface model, and a wound healing scratch assay as well as for their ability to permeate the skin barrier and inhibit venom induced cell death. Results...... Of the 14 water extracts and 16 ethanol extracts tested at a concentration of 10 μg/mL, only the ethanol extracts of Tamarindus indica and Paullinia pinnata resulted in a small but significant increase in cell migration of around 10% compared to treatment with buffer after 24 h treatment. The remaining...... extracts showed no effect, or they even delayed the cell migration compared to the treatment with buffer. After 48 h treatment, 10 of the tested extracts showed a decreased cell migration compared to no treatment. At a 100 μg/mL concentration all the extracts inhibited cell migration and five extracts...

  8. An in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers.

    Science.gov (United States)

    Lensing, Cody J; Freeman, Katie T; Schnell, Sathya M; Adank, Danielle N; Speth, Robert C; Haskell-Luevano, Carrie

    2016-04-14

    Pharmacological probes for the melanocortin receptors have been utilized for studying various disease states including cancer, sexual function disorders, Alzheimer's disease, social disorders, cachexia, and obesity. This study focused on the design and synthesis of bivalent ligands to target melanocortin receptor homodimers. Lead ligands increased binding affinity by 14- to 25-fold and increased cAMP signaling potency by 3- to 5-fold compared to their monovalent counterparts. Unexpectedly, different bivalent ligands showed preferences for particular melanocortin receptor subtypes depending on the linker that connected the binding scaffolds, suggesting structural differences between the various dimer subtypes. Homobivalent compound 12 possessed a functional profile that was unique from its monovalent counterpart providing evidence of the discrete effects of bivalent ligands. Lead compound 7 significantly decreased feeding in mice after intracerebroventricular administration. To the best of our knowledge, this is the first report of a melanocortin bivalent ligand's in vivo physiological effects.

  9. Preparation, characterization and investigation of in vitro and in vivo biological properties of strontium-modified calcium phosphate cement for bone defect repair

    Directory of Open Access Journals (Sweden)

    Reza Masaeli

    2015-12-01

    Full Text Available Background and Aims: The aim of this study was to evaluate the invitro and invivo performance of a 3 wt% of strontium additive hydroxyapatite calcium phosphate cements (CPC. Materials and Methods: The prepared calcium phosphate cement was characterized with XRD, FTIR, setting time, STA and in vitro and in vivo biological analyses. The MTT assay ALP activities as in vitro study and radiological and histological examinations as in vivo study between the three groups of 3 wt% Sr-HA/CPC, CPC and control were performed and compared. Data were analyzed using T-test and One-way ANOVA. Results: XRD analysis demonstrated that by increasing the ratio of Powder/Liquid (P/L, the crystallinity of the prepared cement increased. The substitution of strontium instead of calcium in CPC could also alter the crystal structure, including some structural disorder. However, in the CPC with no strontium hydroxyapatite (Sr-HA, no significant increase in the crystallinity was observed. SEM observations revealed CPC with increasing P/L ratio, the formation of hydroxyapatite crystals arising from the interaction of solid and liquid phase of cement was decreased. Also, the addition of Sr within Ca site culminated in a dramatic increase in crystallinity of hydroxyapatite. In vitro biological properties ascertained that addition of 3 wt. % Sr-HA into CPC enhanced MTT assay and ALP activity, which could be due to the presence of strontium ions. The histological study showed that greater remodeling was seen at 4 weeks after implantation when the 3 wt% Sr-HA/CPC was used. Conclusion: The obtained results cleared that CPC can be a potential candidate as a carrier with strontium additives for bone remodeling and regeneration.

  10. Two-photon microscopy imaging of thy1GFP-M transgenic mice: a novel animal model to investigate brain dendritic cell subsets in vivo.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    Full Text Available Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype.With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity of dendritic cells (DCs, and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions.

  11. Two-Photon Microscopy Imaging of thy1GFP-M Transgenic Mice: A Novel Animal Model to Investigate Brain Dendritic Cell Subsets In Vivo

    Science.gov (United States)

    Laperchia, Claudia; Allegra Mascaro, Anna L.; Sacconi, Leonardo; Andrioli, Anna; Mattè, Alessandro; De Franceschi, Lucia; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Buffelli, Mario; Pavone, Francesco S.

    2013-01-01

    Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF) microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP) in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype. With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity) of dendritic cells (DCs), and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions. PMID:23409142

  12. Early rehabilitation in sepsis: a prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article

    Directory of Open Access Journals (Sweden)

    Kayambu Geetha

    2011-10-01

    Full Text Available Abstract Background Patients with sepsis syndromes in comparison to general intensive care patients can have worse outcomes for physical function, quality of life and survival. Early intensive care rehabilitation can improve the outcome in general Intensive Care Unit (ICU patients, however no investigations have specifically looked at patients with sepsis syndromes. The 'i-PERFORM Trial' will investigate if early targeted rehabilitation is both safe and effective in patients with sepsis syndromes admitted to ICU. Methods/Design A single-centred blinded randomized controlled trial will be conducted in Brisbane, Australia. Participants (n = 252 will include those ≥ 18 years, mechanically ventilated for ≥ 48 hours and diagnosed with a sepsis syndrome. Participants will be randomised to an intervention arm which will undergo an early targeted rehabilitation program according to the level of arousal, strength and cardiovascular stability and a control group which will receive normal care. The primary outcome measures will be physical function tests on discharge from ICU (The Acute Care Index of Function and The Physical Function ICU Test. Health-related quality of life will be measured using the Short Form-36 and the psychological component will be tested using The Hospital Anxiety and Depression Scale. Secondary measures will include inflammatory biomarkers; Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-α, peripheral blood mitochondrial DNA content and lactate, fat free muscle mass, tissue oxygenation and microcirculatory flow. Discussion The 'i-PERFORM Trial' will determine whether early rehabilitation for patients with sepsis is effective at improving patient outcomes with functional and physiological parameters reflecting long and short-term effects of early exercise and the safety in its application in critical illness. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12610000808044

  13. Short Review on Quantum Key Distribution Protocols.

    Science.gov (United States)

    Giampouris, Dimitris

    2017-01-01

    Cryptographic protocols and mechanisms are widely investigated under the notion of quantum computing. Quantum cryptography offers particular advantages over classical ones, whereas in some cases established protocols have to be revisited in order to maintain their functionality. The purpose of this paper is to provide the basic definitions and review the most important theoretical advancements concerning the BB84 and E91 protocols. It also aims to offer a summary on some key developments on the field of quantum key distribution, closely related with the two aforementioned protocols. The main goal of this study is to provide the necessary background information along with a thorough review on the theoretical aspects of QKD, concentrating on specific protocols. The BB84 and E91 protocols have been chosen because most other protocols are similar to these, a fact that makes them important for the general understanding of how the QKD mechanism functions.

  14. In vivo

    Science.gov (United States)

    Berkowitz, Bruce A; Lenning, Jacob; Khetarpal, Nikita; Tran, Catherine; Wu, Johnny Y; Berri, Ali M; Dernay, Kristin; Haacke, E Mark; Shafie-Khorassani, Fatema; Podolsky, Robert H; Gant, John C; Maimaiti, Shaniya; Thibault, Olivier; Murphy, Geoffrey G; Bennett, Brian M; Roberts, Robin

    2017-09-01

    Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/ T 1 that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal-ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising in vivo paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.-Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. © FASEB.

  15. A systematic review protocol investigating tests for physical or physiological qualities and game-specific skills commonly used in rugby and related sports and their psychometric properties.

    Science.gov (United States)

    Chiwaridzo, Matthew; Ferguson, Gillian D; Smits-Engelsman, Bouwien C M

    2016-07-27

    Scientific focus on rugby has increased over the recent years, providing evidence of the physical or physiological characteristics and game-specific skills needed in the sport. Identification of tests commonly used to measure these characteristics is important for the development of test batteries, which in turn may be used for talent identification and injury prevention programmes. Although there are a number of tests available in the literature to measure physical or physiological variables and game-specific skills, there is limited information available on the psychometric properties of the tests. Therefore, the purpose of this study is to systematically review the literature for tests commonly used in rugby to measure physical or physiological characteristics and rugby-specific skills, documenting evidence of reliability and validity of the identified tests. A systematic review will be conducted. Electronic databases such as Scopus, MEDLINE via EBSCOhost and PubMed, Academic Search Premier, CINAHL and Africa-Wide Information via EBSCOhost will be searched for original research articles published in English from January 1, 1995, to December 31, 2015, using a pre-defined search strategy. The principal investigator will select potentially relevant articles from titles and abstracts. To minimise bias, full text of titles and abstracts deemed potentially relevant will be retrieved and reviewed by two independent reviewers based on the inclusion criteria. Data extraction will be conducted by the principal investigator and verified by two independent reviewers. The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist will be used to assess the methodological quality of the selected studies. Choosing an appropriate test to be included in the screening test battery should be based on sound psychometric properties of the test available. This systematic review will provide an overview of the tests commonly used in rugby union

  16. Psychotherapy integration under scrutiny: investigating the impact of integrating emotion-focused components into a CBT-based approach: a study protocol of a randomized controlled trial.

    Science.gov (United States)

    Babl, Anna; Grosse Holtforth, Martin; Heer, Sara; Lin, Mu; Stähli, Annabarbara; Holstein, Dominique; Belz, Martina; Egenolf, Yvonne; Frischknecht, Eveline; Ramseyer, Fabian; Regli, Daniel; Schmied, Emma; Flückiger, Christoph; Brodbeck, Jeannette; Berger, Thomas; Caspar, Franz

    2016-11-24

    This currently recruiting randomized controlled trial investigates the effects of integrating components of Emotion-Focused Therapy (EFT) into Psychological Therapy (PT), an integrative form of cognitive-behavioral therapy in a manner that is directly mirroring common integrative practice in the sense of assimilative integration. Aims of the study are to understand how both, an existing therapy approach as well as the elements to be integrated, are affected by the integration and to clarify the role of emotional processing as a mediator of therapy outcome. A total of 130 adults with a diagnosed unipolar depressive, anxiety or adjustment disorder (seeking treatment at a psychotherapy outpatient clinic) are randomized to either treatment as usual (PT) with integrated emotion-focused components (TAU + EFT) or PT (TAU). Primary outcome variables are psychopathology and symptom severity at the end of therapy and at follow up; secondary outcome variables are interpersonal problems, psychological wellbeing, quality of life, attainment of individual therapy goals, and emotional competency. Furthermore, process variables such as the quality of the therapeutic relationship are studied as well as aptitude-treatment interactions. Variables are assessed at baseline, after 8 and 16 sessions, at the end of therapy, after 25 ± 3 sessions, and at 6, 12 and 36 month follow-up. Underlying mechanisms of change are investigated. Statistical analyses will be conducted using the appropriate multilevel approaches, mainly two-level regression and growth analysis. The results of this study will indicate whether the integration of emotion-focused elements into treatment as usual increases the effectiveness of Psychological Therapy. If advantages are found, which may be limited to particular variables or subgroups of patients, recommendations for a systematic integration, and caveats if also disadvantages are detected, can be formulated. On a more abstract level, a cognitive

  17. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar

    2013-01-01

    This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each...... as possible. Evaluations show that the proposed protocol provides considerable gains over the standard tree splitting protocol applying SIC. The improvement comes at the expense of an increased feedback and receiver complexity....

  18. The Physical Activity and Redesigned Community Spaces (PARCS Study: Protocol of a natural experiment to investigate the impact of citywide park redesign and renovation

    Directory of Open Access Journals (Sweden)

    Terry T. K. Huang

    2016-11-01

    Full Text Available Abstract Background The built environment plays a critical role in promoting physical activity and health. The association between parks, as a key attribute of the built environment, and physical activity, however, remains inconclusive. This project leverages a natural experiment opportunity to assess the impact of the Community Parks Initiative (CPI, a citywide park redesign and renovation effort in New York City, on physical activity, park usage, psychosocial and mental health, and community wellbeing. Methods The project will use a longitudinal design with matched controls. Thirty intervention park neighborhoods are socio-demographically matched to 20 control park neighborhoods. The study will investigate whether improvements in physical activity, park usage, psychosocial and mental health, and community wellbeing are observed from baseline to 3 years post-renovation among residents in intervention vs. control neighborhoods. Discussion This study represents a rare opportunity to provide robust evidence to further our understanding of the complex relationship between parks and health. Findings will inform future investments in health-oriented urban design policies and offer evidence for addressing health disparities through built environment strategies.

  19. The IGNITE (investigation to guide new insight into translational effectiveness trial: Protocol for a translational study of an evidenced-based wellness program in fire departments

    Directory of Open Access Journals (Sweden)

    MacKinnon David P

    2010-10-01

    Full Text Available Abstract Background Worksites are important locations for interventions to promote health. However, occupational programs with documented efficacy often are not used, and those being implemented have not been studied. The research in this report was funded through the American Reinvestment and Recovery Act Challenge Topic 'Pathways for Translational Research,' to define and prioritize determinants that enable and hinder translation of evidenced-based health interventions in well-defined settings. Methods The IGNITE (investigation to guide new insights for translational effectiveness trial is a prospective cohort study of a worksite wellness and injury reduction program from adoption to final outcomes among 12 fire departments. It will employ a mixed methods strategy to define a translational model. We will assess decision to adopt, installation, use, and outcomes (reach, individual outcomes, and economic effects using onsite measurements, surveys, focus groups, and key informant interviews. Quantitative data will be used to define the model and conduct mediation analysis of each translational phase. Qualitative data will expand on, challenge, and confirm survey findings and allow a more thorough understanding and convergent validity by overcoming biases in qualitative and quantitative methods used alone. Discussion Findings will inform worksite wellness in fire departments. The resultant prioritized influences and model of effective translation can be validated and manipulated in these and other settings to more efficiently move science to service.

  20. Study protocol

    DEFF Research Database (Denmark)

    Smith, Benjamin E; Hendrick, Paul; Bateman, Marcus

    2017-01-01

    and acceptability of conducting a definitive RCT which will evaluate the clinical and cost-effectiveness of a loaded self-managed exercise programme for people with patellofemoral pain. METHOD: This is a single-centred, multiphase, sequential, mixed-methods trial that will evaluate the feasibility of running...... that target movements and activities patients find fearful and painful. High-quality research on exercise prescription in relation to pain mechanisms, not directed at specific tissue pathology, and dose response clearly warrants further investigation. Our primary aim is to establish the feasibility...... a definitive large-scale randomised controlled trial of a loaded self-managed exercise programme versus usual physiotherapy. Initially, 8-10 participants with a minimum 3-month history of PFP will be recruited from an NHS physiotherapy waiting list and interviewed. Participants will be invited to discuss...

  1. An investigation of the predictors of photoprotection and UVR dose to the face in patients with XP: a protocol using observational mixed methods.

    Science.gov (United States)

    Walburn, Jessica; Sarkany, Robert; Norton, Sam; Foster, Lesley; Morgan, Myfanwy; Sainsbury, Kirby; Araújo-Soares, Vera; Anderson, Rebecca; Garrood, Isabel; Heydenreich, Jakob; Sniehotta, Falko F; Vieira, Rute; Wulf, Hans Christian; Weinman, John

    2017-08-21

    Xeroderma pigmentosum (XP) is a rare genetic condition caused by defective nucleotide excision repair and characterised by skin cancer, ocular and neurological involvement. Stringent ultraviolet protection is the only way to prevent skin cancer. Despite the risks, some patients' photoprotection is poor, with a potentially devastating impact on their prognosis. The aim of this research is to identify disease-specific and psychosocial predictors of photoprotection behaviour and ultraviolet radiation (UVR) dose to the face. Mixed methods research based on 45 UK patients will involve qualitative interviews to identify individuals' experience of XP and the influences on their photoprotection behaviours and a cross-sectional quantitative survey to assess biopsychosocial correlates of these behaviours at baseline. This will be followed by objective measurement of UVR exposure for 21 days by wrist-worn dosimeter and daily recording of photoprotection behaviours and psychological variables for up to 50 days in the summer months. This novel methodology will enable UVR dose reaching the face to be calculated and analysed as a clinically relevant endpoint. A range of qualitative and quantitative analytical approaches will be used, reflecting the mixed methods (eg, cross-sectional qualitative interviews, n-of-1 studies). Framework analysis will be used to analyse the qualitative interviews; mixed-effects longitudinal models will be used to examine the association of clinical and psychosocial factors with the average daily UVR dose; dynamic logistic regression models will be used to investigate participant-specific psychosocial factors associated with photoprotection behaviours. This research has been approved by Camden and King's Cross Research Ethics Committee 15/LO/1395. The findings will be published in peer-reviewed journals and presented at national and international scientific conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of

  2. The Karachi intracranial stenosis study (KISS Protocol: An urban multicenter case-control investigation reporting the clinical, radiologic and biochemical associations of intracranial stenosis in Pakistan

    Directory of Open Access Journals (Sweden)

    Makki Karim

    2009-07-01

    Full Text Available Abstract Background Intracranial stenosis is the most common cause of stroke among Asians. It has a poor prognosis with a high rate of recurrence. No effective medical or surgical treatment modality has been developed for the treatment of stroke due to intracranial stenosis. We aim to identify risk factors and biomarkers for intracranial stenosis and to develop techniques such as use of transcranial doppler to help diagnose intracranial stenosis in a cost-effective manner. Methods/Design The Karachi Intracranial Stenosis Study (KISS is a prospective, observational, case-control study to describe the clinical features and determine the risk factors of patients with stroke due to intracranial stenosis and compare them to those with stroke due to other etiologies as well as to unaffected individuals. We plan to recruit 200 patients with stroke due to intracranial stenosis and two control groups each of 150 matched individuals. The first set of controls will include patients with ischemic stroke that is due to other atherosclerotic mechanisms specifically lacunar and cardioembolic strokes. The second group will consist of stroke free individuals. Standardized interviews will be conducted to determine demographic, medical, social, and behavioral variables along with baseline medications. Mandatory procedures for inclusion in the study are clinical confirmation of stroke by a healthcare professional within 72 hours of onset, 12 lead electrocardiogram, and neuroimaging. In addition, lipid profile, serum glucose, creatinine and HbA1C will be measured in all participants. Ancillary tests will include carotid ultrasound, transcranial doppler and magnetic resonance or computed tomography angiogram to rule out concurrent carotid disease. Echocardiogram and other additional investigations will be performed at these centers at the discretion of the regional physicians. Discussion The results of this study will help inform locally relevant clinical guidelines

  3. CERAMENT treatment of fracture defects (CERTiFy): protocol for a prospective, multicenter, randomized study investigating the use of CERAMENT™ BONE VOID FILLER in tibial plateau fractures.

    Science.gov (United States)

    Nusselt, Thomas; Hofmann, Alexander; Wachtlin, Daniel; Gorbulev, Stanislav; Rommens, Pol Maria

    2014-03-08

    Bone graft substitutes are widely used for reconstruction of posttraumatic bone defects. However, their clinical significance in comparison to autologous bone grafting, the gold-standard in reconstruction of larger bone defects, still remains under debate. This prospective, randomized, controlled clinical study investigates the differences in pain, quality of life, and cost of care in the treatment of tibia plateau fractures-associated bone defects using either autologous bone grafting or bioresorbable hydroxyapatite/calcium sulphate cement (CERAMENT™|BONE VOID FILLER (CBVF)). CERTiFy (CERament™ Treatment of Fracture defects) is a prospective, multicenter, controlled, randomized trial. We plan to enroll 136 patients with fresh traumatic depression fractures of the proximal tibia (types AO 41-B2 and AO 41-B3) in 13 participating centers in Germany. Patients will be randomized to receive either autologous iliac crest bone graft or CBVF after reduction and osteosynthesis of the fracture to reconstruct the subchondral bone defect and prevent the subsidence of the articular surface. The primary outcome is the SF-12 Physical Component Summary at week 26. The co-primary endpoint is the pain level 26 weeks after surgery measured by a visual analog scale. The SF-12 Mental Component Summary after 26 weeks and costs of care will serve as key secondary endpoints. The study is designed to show non-inferiority of the CBVF treatment to the autologous iliac crest bone graft with respect to the physical component of quality of life. The pain level at 26 weeks after surgery is expected to be lower in the CERAMENT bone void filler treatment group. CERTiFy is the first randomized multicenter clinical trial designed to compare quality of life, pain, and cost of care in the use of the CBVF and the autologous iliac crest bone graft in the treatment of tibia plateau fractures. The results are expected to influence future treatment recommendations. ClinicalTrials.gov: NCT01828905.

  4. An Investigation into the Scale and Impact of Self-Reported Foot Problems Associated with Systemic Lupus Erythematosus: A Study Protocol and Survey Questionnaire Development.

    Science.gov (United States)

    Williams, Anita Ellen; Cherry, Lindsey; Blake, Alison; Alcacer-Pitarch, Begonya; Edwards, Christopher; Hopkinson, Neil; Vital, Edward; Teh, Lee-Suan

    2016-06-01

    Systemic lupus erythematosus (SLE) can manifest with arthralgia and myalgia, and, in severe cases, disorganization of the joints and tendon rupture. Further, Raynaud's phenomenon and other circulatory problems such as vasculitis have been reported, and may be associated with loss of sensation and ulcers. Associated with impaired peripheral neurovascular function there is the potential for changes in tissue viability leading to thinning of the skin or callus formation. In addition, resistance to infections may be reduced, such as fungal infection of the skin and nails, bacterial infection associated with wounds and viral infections such as verruca. There is a dearth of evidence for the effects of SLE in the foot, the prevalence of foot problems in SLE and the impact of these on the individual. In addition, it is not known if people with SLE and foot problems have access to specialist care through foot health services. Hence, there is a need to investigate the scale of foot problems associated with SLE. In order to achieve this, a questionnaire needs to be developed in order to carry out a national survey in England. The items required for the questionnaire were generated using a focus group, which comprised patient advisers with SLE, consultants who specialized in SLE, specialist rheumatology podiatrists and specialist rheumatology nurses. From this consensus approach to the item generation, the draft questionnaire was developed with agreement on themes, question format and overall structure. Additionally, the Manchester Pain and Disability Questionnaire was included in order to capture levels of pain and associated disability. An iterative process followed, with feedback from the focus group reducing the number of other items from 53, until the penultimate version of questionnaire was produced with 50 items. Following on from this, a process of cognitive debriefing was used with two people with SLE who were naïve to the questionnaire. Minor changes to two

  5. Protocol for a randomised controlled trial investigating self-help email messages for sub-threshold depression: the Mood Memos study

    Directory of Open Access Journals (Sweden)

    Mackinnon Andrew J

    2011-01-01

    Full Text Available Abstract Background Sub-threshold depression is common, impairs functioning, and increases the risk of developing major depression. Although psychological treatments have been investigated for sub-threshold depression, they are costly. A less costly alternative could be an educational health promotion campaign about effective self-help for depression symptoms. The aim of the study is to test the efficacy of a low-cost email-based mental health promotion campaign in changing self-help behaviour and preventing more severe depression in adults with sub-threshold depression. Methods/Design The project is a randomised controlled trial of an automated preventive email-intervention aimed at people with sub-threshold depression. Adults aged 18+ with sub-threshold depression (as measured with the Patient Health Questionnaire-9, who are not already receiving professional treatment for depression, are eligible for admission to the study. Internet users will sign up via the study website http://www.moodmemos.com and be randomly allocated to receive emails twice weekly for six weeks containing either self-help coping advice or general information about depression as a control. Outcomes will be assessed at the start, midpoint, and end of the intervention, as well as six months later. Outcomes assessed include symptoms, incidence of major depression, psychological distress, social and occupational functioning, coping strategies, and coping self-efficacy. The primary hypothesis is that the Mood Memo emails containing coping strategies will reduce depression symptoms and be better at preventing major depression than the control emails that contain general information about depression. Discussion Promotion of actions an individual can take to prevent physical disease is a technique often used in public health. This study applies this approach to mental health, and explores whether a low-cost, easily disseminated email-based campaign can improve self-help coping

  6. Investigating the (cost-) effectiveness of attention bias modification (ABM) for outpatients with major depressive disorder (MDD): a randomized controlled trial protocol.

    Science.gov (United States)

    Ferrari, Gina R A; Becker, Eni S; Smit, Filip; Rinck, Mike; Spijker, Jan

    2016-11-03

    quality of life and costs. This is the first study investigating the long-term effects of ABM in adult outpatients with MDD, alongside an economic evaluation. Next to exploring the mechanism underlying ABM effects, this study provides first insight into the effects of combining ABM and UC and the potential implementation of ABM in clinical practice. Trialregister.nl, NTR5285 . Registered 20 July 2015.

  7. The influence of raw and processed garlic and onions on plasma classical and non-classical atherosclerosis indices: investigations in vitro and in vivo.

    Science.gov (United States)

    Gorinstein, Shela; Leontowicz, Hanna; Leontowicz, Maria; Jastrzebski, Zenon; Najman, Katarzyna; Tashma, Zev; Katrich, Elena; Heo, Buk-Gu; Cho, Ja-Yong; Park, Yun-Jum; Trakhtenberg, Simon

    2010-05-01

    Garlic and white and red varieties of onion were subjected to processing by a variety of culinary methods, and bioactive compounds then determined. For in vivo studies, 84 male Wistar rats were randomly divided into 14 diet groups, each of six rats, including two control groups (one with no supplementation and one with cholesterol supplementation only). During the 30-day trial, the basal diets of the other 12 groups were supplemented with 1% cholesterol and raw or processed vegetables. Both raw red onion and red onion subjected to blanching for 90 s hindered the rise in plasma lipids more than the other vegetables studied in the supplemented diets. The decrease in antioxidant activity compared to the cholesterol-supplemented control group was significantly less for the group fed with red onion subjected to blanching for 90 s. No histological changes were detected in the studied organs of rats that had been fed cholesterol. In conclusion, blanching for 90 s most fully preserved the bioactive compounds and antioxidant potentials, and hindered the rise in plasma lipid levels and the decrease in plasma antioxidant activity of rats fed cholesterol. Alkaline phosphatase levels correlated with classical atherosclerosis indices, and determination of alkaline phosphatase is suggested as an additional index in atherosclerosis testing. Copyright (c) 2009 John Wiley & Sons, Ltd.

  8. Investigation of silicon carbon nitride nanocomposite films as a wear resistant layer in vitro and in vivo for joint replacement applications.

    Science.gov (United States)

    Liang, Y; Liu, D G; Bai, W Q; Tu, J P

    2017-05-01

    Silicon-contained CNx nanocomposite films were prepared using the ion beam assisted magnetron sputtering under different nitrogen gas pressure. With increase of the nitrogen pressure, silicon and nitrogen content of the CNx films drastically increase, and is saturated as the PN2 reach about 40%. Surface roughness and the contact angle are increase, while the friction coefficient decreased. The CNx film with 5.7at.% Si content possess the lowest friction coefficient of only 0.07, and exhibited the best tribological properties. The impact of CNx films with different silicon content on the growth and the activation of osteoblasts were compared to that of Ti6Al4V. The incorporation of silicon in the CNx film also showed an increase cell adhesion. Bonding structure and surface energy were determined to be the factors contributing to the improved biocompatibility. Macrophages attached to 5.7at.% Si contained CNx films down regulated their production of cytokines and chemokines. Moreover, employed with Si contained CNx coated joint replacements, which were implanted subcutaneously into Sprague-Dawley mice for up to 36days, the tissue reaction and capsule formation was significantly decreased compared to that of Ti6Al4V. A mouse implantation study demonstrated the excellent in vivo biocompatibility and functional reliability of wear resist layer for joint replacements with a Si doped a-CNx coating for 36days. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A vibration investigation of a flat surface contact to skull bone for direct bone conduction transmission in sheep skulls in vivo.

    Science.gov (United States)

    Taghavi, Hamidreza; Håkansson, Bo; Eeg-Olofsson, Måns; Johansson, Carina B; Tjellström, Anders; Reinfeldt, Sabine; Bergqvist, Tomas; Olsson, Joakim

    2013-06-01

    Bone conduction implant (BCI) attached with a flat surface contact will offer efficient and linear vibration transmission over time. Despite that percutaneous bone conduction devices (PBCD) are successful in treating patients with conductive hearing loss, there are some drawbacks related to the need of a permanent skin penetration. The BCI system is designed as an alternative to the PBCD because it leaves the skin intact. BCI dummy implants were installed in 3 sheep skulls in vivo to study the vibration transmission characteristics over time. Mechanical point impedances and vibration transfer response functions of the BCI implants were measured at the time of surgery and after a healing period of 8 months. In 1 sheep both implants healed without complications. In the other 2 sheep, the implants were either partially loose or lost to follow up. In the sheep with stable implants, it was found by the resonance frequency shift of the mechanical point impedance that a firmer integration between the implant and bone tissue as seen in osseointegrated surfaces developed over time. It was also shown that the transcranial vibration transmission remains stable and linear. Providing bone chips in the contact between the implant and the bone did not enhance vibration transmission. The surgical procedure for installing the BCI dummy implants was uneventful. The mechanical point impedances and vibration transfer response functions indicate that the BCI implants integrate and that transmission conditions remain stable over time.

  10. In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection.

    Directory of Open Access Journals (Sweden)

    Cristiane França da Silva

    Full Text Available Chagas disease is caused by infection with the intracellular protozoan parasite Trypanosoma cruzi. At present, nifurtimox and benznidazole, both compounds developed empirically over four decades ago, represent the chemotherapeutic arsenal for treating this highly neglected disease. However, both drugs present variable efficacy depending on the geographical area and the occurrence of natural resistance, and are poorly effective against the later chronic stage. As a part of a search for new therapeutic opportunities to treat chagasic patients, pre-clinical studies were performed to characterize the activity of a novel arylimidamide (AIA--DB1831 (hydrochloride salt and DB1965 (mesylate salt against T. cruzi. These AIAs displayed a high trypanocidal effect in vitro against both relevant forms in mammalian hosts, exhibiting a high selectivity index and a very high efficacy (IC(50 value/48 h of 5-40 nM against intracellular parasites. DB1965 shows high activity in vivo in acute experimental models (mouse of T. cruzi, showing a similar effect to benznidazole (Bz when compared under a scheme of 10 daily consecutive doses with 12.5 mg/kg. Although no parasitological cure was observed after treating with 20 daily consecutive doses, a combined dosage of DB1965 (5 mg/kg with Bz (50 mg/kg resulted in parasitaemia clearance and 100% animal survival. In summary, our present data confirmed that aryimidamides represent promising new chemical entities against T. cruzi in therapeutic schemes using the AIA alone or in combination with other drugs, like benznidazole.

  11. Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

    Directory of Open Access Journals (Sweden)

    Sidramappa Mallikarjun Chickpetty

    2013-06-01

    Full Text Available The purpose of this research study was to develop 5-fluorouracil compression coated tablets by using biodegradable polysaccharide polymer locust bean gum (LBG and hydroxyl propyl methyl cellulose (HPMC as coating materials. The fast disintegrating core tablets containing 50 mg of 5-fluorouracil were compression coated with LBG and HPMC in different ratios (8:1, 7:2 and 6:3 with a coat weight of 300, 400 and 500 mg. In vitro dissolution data indicated that the formulation (CLH63 with a coat weight of 500 mg containing LBG and HPMC in the ratio 6:3 gave the best release profile (0% in first 5 hour and 96.18% in 24 hours. DSC and FTIR results indicated no possibility of interaction between drug and polymers or other excipients. In vivo human X-ray studies revealed that formulation CLH63 was able to resist breakdown in the stomach and small intestine. The disintegration of the tablet occurred in the colon between 8 to 16 hours of post dose. By the present study, it can be concluded that the LBG and HPMC based compression coated tablets of 5-fluorouracil will be useful strategy for colonic delivery of 5-fluorouracil without being released in upper gastrointestinal region for the safe and effective management of colon cancer.

  12. A protocol for investigation of the effects of outdoor air pollution on stroke incidence, phenotypes and survival using the South London Stroke Register

    Directory of Open Access Journals (Sweden)

    Smeeton Nigel

    2006-03-01

    Full Text Available Abstract Stroke is a major cause of death and disability. About 5.3 million people die every year from stroke worldwide with over 9 million people surviving at any one time after suffering a stroke. About 1 in 4 men and 1 in 5 women aged 45 years will suffer a stroke if they live to their 85th year. It is estimated that by 2023 there will be an absolute increase in the number of people experiencing a first ever stroke of about 30% compared with 1983. In the UK, stroke is the third commonest cause of death and the most common cause of adult physical disability and consumes 5% of the health and social services budget. Stroke is assuming strategic public health importance because of increased awareness in society, an ageing population and emerging new treatments. It is an NHS health service and research priority, being identified as a target in Our Healthier Nation and the NSF for Older People for prevention and risk factor control and in the NHS Plan as a disease requiring intermediate care planning and reduction in inequalities of care. Whilst a number of risk factors for stroke are well known (e.g. increasing age, ethnicity, socioeconomic deprivation, hypertension, the potential importance of outdoor air pollution as a modifiable risk factor is much less well recognised. This is because studies to date are inconclusive or have methodological limitations. In Sheffield, we estimated that 11% of stroke deaths may be linked to current levels of outdoor air pollution and this high figure is explained by the fact that so many people are exposed to air pollution. We plan to study the effects of outdoor air pollution on stroke using a series of epidemiological (i.e. population based studies. The purpose of this project is: • to examine if short term increases in pollution can trigger a stroke in susceptible individuals; • to investigate if the occurrence of stroke is higher amongst people living in more polluted areas (which would be explained by a

  13. An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer

    Directory of Open Access Journals (Sweden)

    Mohan Daburkar

    2014-01-01

    Full Text Available Aim: To examine the preventive effect of Aloe vera gel ethanolic extract using diabetic foot ulcer (DFUs protocol in Wistar rats. Materials and Methods: Male Wistar rats were divided into untreated control (Group I, untreated DFUs (Group II, DFUs treated with A. vera gel ethanolic extract (Group III, DFUs treated with topical A. vera gel (Group IV, DFUs treated with A. vera gel ethanolic extract and topical A. vera gel (Group V. The rats in the treatment groups were daily administered the A. vera gel and ethanolic extract for 9 days. Fasting blood glucose levels and percentage of wound ulcer contraction were measured on day 3, 6, and 9. Statistical Analysis used: The results are expressed as a mean ± Standard Error Mean (SEM. Data were analyzed using one-way analysis of variance (ANOVA after Newman-Keuls test. P < 0.05 were considered statistically significant in all cases. Results: Oral administration of A. vera gel ethanolic extract at a dose of 300 mg/kg body weight per day to diabetic rats for a period of 9 days resulted in a significant reduction in fasting blood glucose and a significant improvement in plasma insulin. Topical application of A. vera gel at a dose 30 mg/kg body weight per day to streptozotocin (STZ-induced diabetic rats for a period of 9 days resulted in no change in blood glucose and plasma insulin. Oral administration as well as topical application of A. vera gel ethanolic extract and gel significantly reduced the blood glucose, improved the plasma insulin, and significantly increased DNA and glycosaminoglycans (GAGs to improve the wound ulcer healing as well as the breaking strength on day 9. Conclusions: Present findings provide a scientific rationale for the use of A. vera gel ethanolic extract, and showed that the gel attenuated the diabetic foot wound in rats.

  14. Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

    Science.gov (United States)

    Ross, Clare L; Galloway-Phillipps, Neil; Armstrong, Paul C; Mitchell, Jane A; Warner, Timothy D; Brearley, Christopher; Ito, Mari; Tunstall, Tanushree; Elkin, Sarah; Kon, Onn Min; Hansel, Trevor T; Paul-Clark, Mark J

    2015-01-01

    Introduction Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. Ethics and dissemination This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals

  15. Ionic Liquid - Microemulsions Assisting in the Transdermal Delivery of Dencichine: Preparation, In-vitro and In-vivo Evaluations, and Investigation of the Permeation Mechanism.

    Science.gov (United States)

    Wang, Chengxiao; Zhu, Junxiao; Zhang, Ding; Yang, Ye; Zheng, Luyao; Qu, Yuan; Yang, Xiaoyan; Cui, Xiuming

    2017-11-02

    A novel microemulsion was developed and characterized for topical delivery of Dencichine (Den). Two imidazaolium ionic liquid, 1-hydroxyethyl-3-methylimidazolium chloride ([HOEIM]Cl) and 1-butyl-3-methylimidazolium dodecanesulfate ([BMIM]C12SO3) were incorporated into the aqueous and surfactant phases respectively for the remarkable enhancement on skin permeation. The nano-carrier was developed and optimized based on a pseudo-ternary phase diagram. The optimized formulation was composed of 50% water/[HOEIM]Cl mix (1:1) as water phase, 20% Tween 80/[BMIM]C12SO3 mix (1:1) as surfactant, 10% propylene glycol as co-surfactant and 20% IPM as oil phase. The o/w microemulsion was then characterized for droplets sizes (47.7±1.5nm), zeta potential (-14.83±3.64mV), viscosity (31±4 mPa) and pH (6.71±0.04). In-vitro skin permeation assay suggested the strong enhancement of ILs formulation on the topical delivery of Den, which was approximately 10-fold that of the drug aqueous solution. It was found that the nano-carrier can reduce the skin barrier properties by disrupting the regular and compact arrangements of corneocytes, and moderating the surface properties of the stratum corneum, as evidenced by Transdermal Water Loss Evaluation (TEWL), Differential Scanning Calorimetery (DSC) and attenuated total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR). Furthermore, the in-vivo pharmacodynamic evaluation indicated the significant hemostatic activity of Den by the topical application of the vehicle. Additionally, the formulation showed minor cell toxicity and skin irritation. Therefore, our work suggested that the ionic liquid microemulsion can be a promising nano-scale vehicle for the topical application of Den to produce desirable pharmacological effects. Copyright © 2017. Published by Elsevier B.V.

  16. Formulation design of a highly hygroscopic drug (pyridostigmine bromide) for its hygroscopic character improvement and investigation of in vitro/in vivo dissolution properties.

    Science.gov (United States)

    Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

    2007-04-01

    Pyridostigmine bromide (PB) sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods using Taguchi experimental and 2(3) full factorial design. In vitro studies, the 2(3) full factorial design was utilized to search for the optimal SR pellets with specific release rate at different time intervals (release percent of 2, 6, 12, and 24 hr were 6.24, 33.48, 75.18, and 95.26%, respectively) which followed a zero-order mechanism (n=0.93). The results of moisture absorption by Karl Fischer has shown the optimum SR pellets at 25 degrees C/60% RH, 30 degrees C/65% RH, and 40 degrees C/75% RH chambers from 1 hr-4 weeks, attributing that the moisture absorption was not significantly increased. In the in vivo study, the results of the bioavailability data showed the Tmax (from 0.65+/-0.082 hr-4.82+/-2.12 hr) and AUC0-30 hr (from 734.88+/-230.68 ng/mL.hr-1454.86+/-319.28 ng/mL.hr) were prolonged and increased, as well as Cmax (from 251.87+/-27.51 ng/mL-115.08+/-14.87 ng/mL) was decreased for optimum SR-PB pellets when compared with commercial immediate-release (IR) tablets. Furthermore, a good linear regression relationship (r=0.9943) was observed between the fraction dissolution and fraction absorption for the optimum SR pellets. In this study, the formulation design not only improved the hygroscopic character of PB but also achieved the SR effect.

  17. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with sup 9 sup 9 sup m Tc-MIBI in an in vivo tumoral model

    CERN Document Server

    Faintuch, B L

    1997-01-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with sup 9 sup 9 sup m Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, sup 9 sup 9 sup m Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that sup 9 sup 9 sup m Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors.

  18. An Investigation into Kyoto Protocol's Clean Development ...

    African Journals Online (AJOL)

    CDM) as a transition mechanism to Kenya's green economy and the contribution of CDM projects towards sustainable development in Kenya. Accordingly, a positive checklist approach to sustainable development indicators was applied as ...

  19. Guided bone regeneration of non-contained mandibular buccal bone defects using deproteinized bovine bone mineral and a collagen membrane: an experimental in vivo investigation.

    Science.gov (United States)

    Sanz, Mariano; Ferrantino, Luca; Vignoletti, Fabio; de Sanctis, Massimo; Berglundh, Tord

    2017-11-01

    The aim of this pre-clinical in vivo study was to analyse different stages of wound healing after guided bone regeneration in non-contained mandibular buccal bone defects. Eighteen female beagle dogs, between 1.5 and 2 years old, were used. Buccal bone defects were created in the mandible following extraction of the mesial roots of M1, P4, the distal root of P3 and booth roots of P2. Augmentation procedures of the healed defects were performed 3 months later using a bone replacement graft (T1), an absorbable collagen membrane (T2) or a combination of both procedures (T3). Using a randomized block study design, four stages of healing in two groups of dogs were examined (4 days, 2, 6 weeks and 3 months). The animals were euthanized, and biopsies obtained at the end of each of the study periods were prepared for histological examination. The different reconstructive procedures resulted in regenerated tissue compartments of varying size that contained newly formed bone, non-mineralized tissue and bone augmentation biomaterial when a bone replacement graft was used. While the proportions of mineralized tissue increased and non-mineralized tissue decreased over time in the three groups, the changes in proportions of the DBBM material were small. Initial defect depth, healing time and treatment group significantly influenced the percentage of mineralized tissue obtained. The multivariate multilevel analysis showed that significantly larger area proportions of mineralized tissue were obtained when the T2 sites were compared with T1 and T3 sites, what highlights the importance of the barrier membrane effect for attaining new bone formation. Only in the larger size defects (M1) total ROI at T3 and T1 sites was significantly larger than at T2, what highlights the importance of using a bone replacement graft as a space maintenance scaffold. It is suggested that healing following augmentation of non-contained buccal bone defects was characterized by a gradual shift in the

  20. Systematically experimental investigation on carcinogenesis or tumorigenicity of VERO cell lines of different karyotypes in nude mice in vivo used for viral vaccine manufacture.

    Science.gov (United States)

    Zhang, De-Li; Ji, Liang; Li, Liu-Jin; Huang, Gao-Sheng

    2004-07-01

    Many cell lines used for vaccine production have a potentially strong tumorigenic character. Some of those routinely used need to be checked at different passage numbers for this characteristic. Using HeLa cell cultures as positive controls, and primary canine kidney cell (CKC) or feline kidney cell (FKC) cultures purified in vitro on passage three as negative controls, the tumorigenicity of VERO cell sublines was tested in 219 nude mice. The master cell stocks (MCS) and working cell banks (WCB) of eight strains of VERO African green monkey kidney cell (AGMKC) line used for canine, feline and mink vaccine preparation were established in China. The hypo-tetra-ploid JA or hyper-diploid KA strain of VERO line was highly tumorigenic. These data showed a variable chromosome karyotype of VERO line, and contraindicated the use of JA or KA strain of VERO line for the preparation of attenuated viral vaccines. JA or KA strain of VERO line could be a substitute for HeLa line as a positive-control malignant tumor (MT) cell model. The non-carcinogenic YB, JC, M and JB strains of VERO line were therefore selected for the preparation of modified live rabies viral vaccine in place of BHK-21. The cell sub-lines are comparatively stable in terms of their heritable characters, and show little significant changes between passages. In summary, we have found that: 1) the tumorigenicity of cell line is different among different-karyotypic cells; 2) it is the genetic characteristics of chromosomes of cell lines that determines their tumorigenicity, but with species-specific carcinogenicity; 3) the chromosome number variation of cell lines has positive relationship with their carcinogenesis; 4) highly variable strains of tumor cell line can be selected quickly and successfully in nude mice by alternate cultivation in vitro and in vivo. Malignant rhabdoid tumor (MRT) was evolved in nude mice inoculated with violently variable HeLa or VERO cells. The importance of assessing the

  1. Tumorigenic potential of pituitary tumor transforming gene (PTTG) in vivo investigated using a transgenic mouse model, and effects of cross breeding with p53 (+/-) transgenic mice.

    Science.gov (United States)

    Fong, Miranda Y; Farghaly, Hanan; Kakar, Sham S

    2012-11-20

    Pituitary tumor-transforming gene (PTTG) is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis. Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals. PTTG transgenic offspring (TgPTTG) were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells. Tumorigenesis is a multi-step process, often requiring

  2. Tumorigenic potential of pituitary tumor transforming gene (PTTG in vivo investigated using a transgenic mouse model, and effects of cross breeding with p53 (+/− transgenic mice

    Directory of Open Access Journals (Sweden)

    Fong Miranda Y

    2012-11-01

    Full Text Available Abstract Background Pituitary tumor-transforming gene (PTTG is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis. Methods Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals. Results PTTG transgenic offspring (TgPTTG were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells

  3. Automating Security Protocol Analysis

    National Research Council Canada - National Science Library

    Mancini, Stephen

    2004-01-01

    .... Because of this, analysis of the protocol outside the encryption is becoming more important. Recent work by Joshua Guttman and others 9 have identified several properties that good protocols often exhibit...

  4. Yoga-teaching protocol adapted for children with visual impairment

    Directory of Open Access Journals (Sweden)

    Soubhagyalaxmi Mohanty

    2016-01-01

    Conclusions: Specially designed protocol may pave the way to impart yoga in an exciting and comfortable way to children with VI. More studies are needed to further investigate the effectiveness of this new yoga protocol in similar settings.

  5. Use of WGS data for investigation of a long-term NDM-1-producing Citrobacter freundii outbreak and secondary in vivo spread of blaNDM-1 to Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca.

    Science.gov (United States)

    Hammerum, Anette M; Hansen, Frank; Nielsen, Hans Linde; Jakobsen, Lotte; Stegger, Marc; Andersen, Paal S; Jensen, Paw; Nielsen, Tue Kjærgaard; Hansen, Lars Hestbjerg; Hasman, Henrik; Fuglsang-Damgaard, David

    2016-11-01

    An outbreak of NDM-1-producing Citrobacter freundii and possible secondary in vivo spread of bla NDM-1 to other Enterobacteriaceae were investigated. From October 2012 to March 2015, meropenem-resistant Enterobacteriaceae were detected in 45 samples from seven patients at Aalborg University Hospital, Aalborg, Denmark. In silico resistance genes, Inc plasmid types and STs (MLST) were obtained from WGS data from 24 meropenem-resistant isolates (13 C. freundii, 6 Klebsiella pneumoniae, 4 Escherichia coli and 1 Klebsiella oxytoca) and 1 meropenem-susceptible K. oxytoca. The sequences of the meropenem-resistant C. freundii isolates were compared by phylogenetic analyses. In vitro susceptibility to 21 antimicrobial agents was tested. Furthermore, in vitro conjugation and plasmid characterization was performed. From the seven patients, 13 highly clonal ST18 NDM-1-producing C. freundii were isolated. The ST18 NDM-1-producing C. freundii isolates were only susceptible to tetracycline, tigecycline, colistin and fosfomycin (except for the C. freundii isolates from Patient 2 and Patient 7, which were additionally resistant to tetracycline). The E. coli and K. pneumoniae from different patients belonged to different STs, indicating in vivo transfer of bla NDM-1 in the individual patients. This was further supported by in vitro conjugation and detection of a 154 kb IncA/C2 plasmid with bla NDM-1 . Patient screenings failed to reveal any additional cases. None of the patients had a history of recent travel abroad and the source of the bla NDM-1 plasmid was unknown. To our knowledge, this is the first report of an NDM-1-producing C. freundii outbreak and secondary in vivo spread of an IncA/C2 plasmid with bla NDM-1 to other Enterobacteriaceae. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with {sup 99m} Tc-MIBI in an in vivo tumoral model; Estudo de marcacao, biodistribuicao e analise compartimental da N-acetil cisteina marcada com Tc-99m. Investigacao comparativa com MIBI-{sup 99m}Tc em modelo tumoral in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Faintuch, Bluma Linkowski

    1997-07-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with {sup 99m} Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, {sup 99m} Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that {sup 99m} Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  7. In vivo near-infrared imaging of fibrin deposition in thromboembolic stroke in mice.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available OBJECTIVES: Thrombus and secondary thrombosis plays a key role in stroke. Recent molecular imaging provides in vivo imaging of activated factor XIII (FXIIIa, an important mediator of thrombosis or fibrinolytic resistance. The present study was to investigate the fibrin deposition in a thromboembolic stroke mice model by FXIIIa-targeted near-infrared fluorescence (NIRF imaging. MATERIALS AND METHODS: The experimental protocol was approved by our institutional animal use committee. Seventy-six C57B/6J mice were subjected to thromboembolic middle cerebral artery occlusion or sham operation. Mice were either intravenously injected with the FXIIIa-targeted probe or control probe. In vivo and ex vivo NIRF imaging were performed thereafter. Probe distribution was assessed with fluorescence microscopy by spectral imaging and quantification system. MR scans were performed to measure lesion volumes in vivo, which were correlated with histology after animal euthanasia. RESULTS: In vivo significant higher fluorescence intensity over the ischemia-affected hemisphere, compared to the contralateral side, was detected in mice that received FXIIIa-targeted probe, but not in the controlled mice. Significantly NIRF signals showed time-dependent processes from 8 to 96 hours after injection of FXIIIa-targeted probes. Ex vivo NIRF image showed an intense fluorescence within the ischemic territory only in mice injected with FXIIIa-targeted probe. The fluorescence microscopy demonstrated distribution of FXIIIa-targeted probe in the ischemic region and nearby micro-vessels, and FXIIIa-targeted probe signals showed good overlap with immune-fluorescent fibrin staining images. There was a significant correlation between total targeted signal from in vivo or ex vivo NIRF images and lesion volume. CONCLUSION: Non-invasive detection of fibrin deposition in ischemic mouse brain using NIRF imaging is feasible and this technique may provide an in vivo experimental tool in

  8. Ex vivo lung perfusion review of a revolutionary technology.

    Science.gov (United States)

    Makdisi, George; Makdisi, Tony; Jarmi, Tambi; Caldeira, Christiano C

    2017-09-01

    Donor lung shortage has been the main reason to the increasing number of patients waiting for lung transplant. Ex vivo lung perfusion (EVLP) is widely expanding technology to assess and prepare the lungs who are considered marginal for transplantation. the outcomes are encouraging and comparable to the lungs transplanted according to the standard criteria. in this article, we will discuss the history of development, the techniques and protocols of ex vivo, and the logics and rationales for ex vivo use.

  9. Blind Collective Signature Protocol

    Directory of Open Access Journals (Sweden)

    Nikolay A. Moldovyan

    2011-06-01

    Full Text Available Using the digital signature (DS scheme specified by Belarusian DS standard there are designed the collective and blind collective DS protocols. Signature formation is performed simultaneously by all of the assigned signers, therefore the proposed protocols can be used also as protocols for simultaneous signing a contract. The proposed blind collective DS protocol represents a particular implementation of the blind multisignature schemes that is a novel type of the signature schemes. The proposed protocols are the first implementations of the multisignature schemes based on Belarusian signature standard.

  10. Full Kinetics and a Mechanistic Investigation of the Green Protocol for Synthesis of β-Aminoketone in the Presence of Saccharose as a Catalyst by a One-Pot Three-Component Reaction

    Directory of Open Access Journals (Sweden)

    Sayyed Mostafa Habibi-Khorassani

    2014-01-01

    Full Text Available For the first time, in a green protocol, an investigation of the kinetics and mechanism of the reaction between benzaldehyde 1, 4-chloroanilinne 2, and acetophenone 3 compounds in the presence of saccharose as a catalyst was performed for generating β-aminoketone. For determining the kinetic parameters, the reaction was monitored by using the UV/Vis spectrophotometry technique. The second order rate constant (k1 was automatically calculated by the standard equations contained within the program. In the studied temperature range, the second order rate constant (ln k1, ln k1/T depended on reciprocal temperature that was in good consistent with Arrhenius and Eyring equations, respectively. These data provided the suitable plots for calculating the activation energy and parameters (Ea, ΔG‡, ΔS‡, and ΔH‡ of the reaction. Furthermore, useful information was obtained from studying the effects of solvent, concentration, and catalyst on the reaction mechanism. The results showed that the first step of the reaction mechanism is a rate determining step (RDS. The obtained experimental data and also the steady state assumption confirmed the proposed mechanism.

  11. Modeling Transport Layer Protocols

    Science.gov (United States)

    Sasnauskas, Raimondas; Weingaertner, Elias

    In a layered communication architecture, transport layer protocols handle the data exchange between processes on different hosts over potentially lossy communication channels. Typically, transport layer protocols are either connection-oriented or are based on the transmission of individual datagrams. Well known transport protocols are the connection-oriented Transmission Control Protocol (TCP) [372] and the User Datagram Protocol (UDP) [370] as well as the Stream Control Transmission Protocol (SCTP) [340] and DCCP, the Datagram Congestion Control Protocol [259]. In this chapter, we focus on the modeling process of the transport layer. While we mostly use TCP and UDP as a base of comparison from this point, we emphasize that the methodologies discussed further on are conferrable to virtually any transport layer in any layered communication architecture.

  12. Nasal toxicological investigations of Carbopol 971P formulation of apomorphine: effects on ciliary beat frequency of human nasal primary cell culture and in vivo on rabbit nasal mucosa.

    Science.gov (United States)

    Ugwoke, M I; Agu, R U; Jorissen, M; Augustijns, P; Sciot, R; Verbeke, N; Kinget, R

    2000-02-01

    The objective of this study was to investigate the nasal toxicity of a mucoadhesive Carbopol 971P formulation of apomorphine. The effects of different concentrations of Carbopol 971P and apomorphine on ciliary beat frequency (CBF) were studied in suspension cultures of human nasal epithelial cells. The rabbit nasal mucosal tolerance of the formulation and its components were investigated using light microscopy. Different groups of the rabbits received twice daily, air puffs, glucose, glucose/apomorphine, Carbopol 971P or Carbopol 971P/apomorphine for 1 week (glucose-treated rabbits) or 1, 2 and 4 weeks (other treatments). Both Carbopol 971P and apomorphine showed both concentration- and time-dependent inhibitory effects on the CBF. The effects on CBF were: apomorphine, 1.0% w/v, irreversible ciliostasis; 0.1 and 0.5% w/v, reversible cilio-inhibition; 0.01%w/v, irreversible cilio-stimulation; and Carbopol 971P, 0.1 and 0.25% w/v, partially-reversible cilio-inhibition. Glucose and glucose/apomorphine physical mixture caused mild inflammation. Carbopol 971P (both with and without apomorphine) caused severe inflammation, which increased with duration of treatment. Necrosis, squamous metaplasia or ciliary degeneration was not observed. Due to the severe inflammation caused by Carbopol 971P with and without apomorphine, we conclude that this polymer is not a suitable carrier for intranasal administration of apomorphine. This is in spite of the reversible effects of Carbopol 971P (0.1 and 0. 25% w/v) and apomorphine (0.1 and 0.5% w/v) on CBF.

  13. A general protocol for the generation of Nanobodies for structural biology

    DEFF Research Database (Denmark)

    Pardon, Els; Laeremans, Toon; Triest, Sarah

    2014-01-01

    There is growing interest in using antibodies as auxiliary tools to crystallize proteins. Here we describe a general protocol for the generation of Nanobodies to be used as crystallization chaperones for the structural investigation of diverse conformational states of flexible (membrane) proteins...... display of in vivo-matured Nanobodies that bind conformational epitopes of functional proteins. Three representative examples illustrate that the outlined procedures are robust, making it possible to solve by Nanobody-assisted X-ray crystallography in a time span of 6-12 months....

  14. Photoactivated In Vivo Proximity Labeling.

    Science.gov (United States)

    Beck, David B; Bonasio, Roberto

    2017-06-19

    Identification of molecular interactions is paramount to understanding how cells function. Most available technologies rely on co-purification of a protein of interest and its binding partners. Therefore, they are limited in their ability to detect low-affinity interactions and cannot be applied to proteins that localize to difficult-to-solubilize cellular compartments. In vivo proximity labeling (IPL) overcomes these obstacles by covalently tagging proteins and RNAs based on their proximity in vivo to a protein of interest. In IPL, a heterobifunctional probe comprising a photoactivatable moiety and biotin is recruited by a monomeric streptavidin tag fused to a protein of interest. Following UV irradiation, candidate interacting proteins and RNAs are covalently biotinylated with tight spatial and temporal control and subsequently recovered using biotin as an affinity handle. Here, we describe experimental protocols to discover novel protein-protein and protein-RNA interactions using IPL. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  15. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    Science.gov (United States)

    Kwon, Jee Young; Koedrith, Preeyaporn; Seo, Young Rok

    2014-01-01

    Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. PMID:25565845

  16. In vivo

    Science.gov (United States)

    Freudenblum, Julia; Iglesias, José A; Hermann, Martin; Walsen, Tanja; Wilfinger, Armin; Meyer, Dirk; Kimmel, Robin A

    2018-02-08

    The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering. © 2018. Published by The Company of Biologists Ltd.

  17. In Vivo

    Science.gov (United States)

    Lau, Melissa; Li, Jianli; Cline, Hollis T

    2017-01-01

    The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet. Confocal imaging indicates that about half of the endfeet appear to appose the vasculature, and time-lapse analysis of NPC proliferation and endfeet-vascular interactions suggest that proliferative activity does not correlate with stable vascular apposition. Together, these findings characterize the neurovascular niche in the developing brain and suggest that, while signaling to NPCs may occur through vascular-derived soluble cues, stable contact between NPC endfeet and the vasculature is not required for developmental neurogenesis.

  18. IN VIVO

    Science.gov (United States)

    Jamila, Nargis; Khan, Naeem; Khan, Amir Atlas; Khan, Imran; Khan, Sadiq Noor; Zakaria, Zainal Amiruddin; Khairuddean, Melati; Osman, Hasnah; Kim, Kyong Su

    2017-01-01

    Garcinia hombroniana , known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract. In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl 4 )/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl 4 . Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1 H, 13 C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract. In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (pIR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents. From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

  19. Investigating the Synergic Effects of Ethanolic Extract of Allium sativum L and Electromagnetic Field with Low Frequency on Angiogenesis in Chick Chorioallantoic Membrane (In Vivo

    Directory of Open Access Journals (Sweden)

    D Sadooghi

    2013-10-01

    Full Text Available Introduction: A number of researches show anti-proliferative effects of EMF on animal cells. In addition to antioxidant properties of garlic,it contains compounds that can inhibit cell proliferation. This study wasconducted to investigate the effects of garlic extract and EMF with low frequency on angiogenesis. Methods: Eighty fertilized eggs were divided into the control group, sham-exposed 1 (treated by normal saline, sham-exposed 2 (in vicinity of switched off EMF, experimental group 1 (treated by concentration 100 μg/ml of garlic extract, experimental group 2 (treated by concentration 200 μg/ml of garlic extract, experimental group 3 (in vicinity of EMF with intensity of 50 gauss, experimental group 4 (treated by concentration 100 μg/ml of garlic extract and EMF with intensity of 50 gauss, experimental group 5 (treated by concentration 200 μg/ml of garlic extract and EMF with intensity of 50 gauss. On the 8th day of incubation, gelatin sponge was placed on the chorioallantoic membrane and experimental groups 1, 2, 4, and 5 were treated with 10 microliters of garlic extract. On the 10th day of incubation, experimental groups 3, 4 and 5 were exposed to EMF for 4 hours. All samples were photographed on the 12th day of incubation and the length and numbers of vessels were analyzed by ANOVA and Tukey statistical tests. Results: The mean number and length of blood vessels in all experimental groups were significantly decreased compared to the control group (p<0.05. Conclusion: Garlic has inhibitory effects on angiogenesis. Moreover, these effects wereamplified by EMF with intensity of 50 gauss.

  20. In Vivo Pharmacodynamic Target Investigation of Two Bacterial Topoisomerase Inhibitors, ACT-387042 and ACT-292706, in the Neutropenic Murine Thigh Model against Streptococcus pneumoniae and Staphylococcus aureus.

    Science.gov (United States)

    Lepak, A J; Seiler, P; Surivet, J P; Ritz, D; Kohl, C; Andes, D R

    2016-06-01

    ACT-387042 and ACT-292706 are two novel bacterial topoisomerase inhibitors with broad-spectrum activity against Gram-positive and -negative bacteria, including methicillin-resistant Staphylococcus aureus and penicillin- and fluoroquinolone-resistant Streptococcus pneumoniae We used the neutropenic murine thigh infection model to characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of these investigational compounds against a group of 10 S. aureus and S. pneumoniae isolates with phenotypic resistance to beta-lactams and fluoroquinolones. The in vitro activities of the two compounds were very similar (MIC range, 0.03 to 0.125 mg/liter). Plasma pharmacokinetics were determined for each compound by using four escalating doses administered by the subcutaneous route. In treatment studies, mice had 10(7.4) to 10(8) CFU/thigh at the start of therapy with ACT-387042 and 10(6.7) to 10(8.3) CFU/thigh at the start of therapy with ACT-292706. A dose-response relationship was observed with all isolates over the dose range. Maximal kill approached 3 to 4 log10 CFU/thigh compared to the burden at the start of therapy for the highest doses examined. There was a strong relationship between the PK/PD index AUC/MIC ratio (area under the concentration-time curve over 24 h in the steady state divided by the MIC) and therapeutic efficacy in the model (R(2), 0.63 to 0.82). The 24-h free-drug AUC/MIC ratios associated with net stasis for ACT-387042 against S. aureus and S. pneumoniae were 43 and 10, respectively. The 24-h free-drug AUC/MIC ratios associated with net stasis for ACT-292706 against S. aureus and S. pneumoniae were 69 and 25, respectively. The stasis PD targets were significantly lower for S. pneumoniae (P < 0.05) for both compounds. The 1-log-kill AUC/MIC ratio targets were ∼2- to 4-fold higher than stasis targets. Methicillin, penicillin, or ciprofloxacin resistance did not alter the magnitude of the AUC/MIC ratio required for efficacy. These results should be

  1. Optimized isolation enables Ex vivo analysis of microglia from various central nervous system regions

    NARCIS (Netherlands)

    De Haas, Alexander H.; Boddeke, Hendricus W. G. M.; Brouwer, Nieske; Biber, Knut

    2007-01-01

    Ex vivo analysis is an accurate and convenient way to study in vivo microglia phenotype and function. However, current microglia isolation protocols for ex vivo analysis show many differences in isolation steps (perfusion, removal of meninges and blood vessels, mechanical dissociation, enzymatic

  2. Detecting Hidden Communications Protocols

    Science.gov (United States)

    2013-02-11

    CFG , we can build a LALR parser to parse the symbolized traffic data sets. After symbolization, we parse the training data sets to estimate a PCFG...HMMs to represent protocols in network, we have one assumption that the protocol has finite state. For context-free grammars ( CFGs ), they are in a...by a CFG , so it is more reasonable to use CFGs to model protocols. We started research with Probabilistic CFGs , where each production rule is

  3. Investigation of Combined Action of Food Supplement's and Ionizing Radiation on the Cytogenetic Damage Induction and Ehrlich Ascite Carcinoma Growth on Mice in Vivo

    Science.gov (United States)

    Sorokina, Svetlana; Zaichkina, Svetlana; Dyukina, Alsu; Rozanova, Olga; Balakin, Vladimir; Peleshko, Vladimir; Romanchenko, Sergey; Smirnova, Helena; Aptikaeva, Gella; Shemyakov, Alexander

    In recent ten years one of the major problems of modern radiobiology is the study of radiation protective mechanisms with the help of different substances as well as activation of internal resources of the organism. Internal resources mean such phenomena as hormesis and adaptive response which represent cell or body reaction on low doses of inducing factors and predetermine their further high dose effect resistance. At present special interest is attracted by studies of biological effects of low-dose-rate high-LET radiation because of searching for new types of radiation for more effective cancer therapy and searching for new methods of radiation protection. Since natural biologically active substances have low toxicity and are capable of affecting physiological processes taking place in human’s organism and increasing organism’s natural defense system, the interest to protective means of vegetal origin and search of special food supplements intensifies every year. The purpose of this study is to investigate the combined influence of food supplement, low dose rate high-LET radiation simulating high-altitude flight conditions and X-ray radiations on radiosensitivity, induction of radiation adaptive response (RAR) and growth of Ehrlich ascite carcinoma as well. Experiments were performed with males of SHK mice at the age of two months. The animals were being irradiated with low-dose-rate high-LET radiation with the dose of 11,6 cGy (0,5 cGy/day) behind the concrete shield of the 70 GeV protons accelerator (Protvino). The X-ray irradiation was carried out on the RTH device with a voltage of 200 kV (1 Gy/min; Pushchino). The diet composition included products containing big amount of biologically active substances, such as: soybeam meat, buckwheat, lettuce leaves and drug of cod-liver oil. Four groups of mice were fed with selected products mentioned above during the whole irradiation period of 22 days. The control groups received the same food without irradiation

  4. Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial.

    Science.gov (United States)

    Rosso-Fernández, Clara; Sojo-Dorado, Jesús; Barriga, Angel; Lavín-Alconero, Lucía; Palacios, Zaira; López-Hernández, Inmaculada; Merino, Vicente; Camean, Manuel; Pascual, Alvaro; Rodríguez-Baño, Jesús

    2015-03-31

    Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects

  5. Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: Investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement

    Science.gov (United States)

    YANG, CHANG; HU, DONG-HUI; FENG, YAN

    2015-01-01

    The aim of the present study was to investigate the chemical composition of the essential oil of Artemisia vestita and to determine the antibacterial activity of the essential oil and its two major components, grandisol and 1,8-cineole, against certain respiratory infection-causing bacterial strains, in vitro and in vivo. The chemical composition of the essential oil was analyzed using gas chromatography-mass spectrometry. A micro-well dilution method was used to determine the minimum inhibition concentration (MIC) values of the essential oil and its major constituents. A model of Streptococcus pyogenes infection in mice was used to determine its in vivo activities. Lung and blood samples were obtained to assess bacterial cell counts. Toxicity evaluation of the essential oil and its components was completed by performing biochemical analysis of the serum, particularly monitoring aspartate transaminase, alanine transaminase, urea and creatinine. The essential oil exhibited potent antibacterial activity, whereas the two major constituents were less potent. The essential oil exhibited MIC values between 20 and 80 μg/ml, while the values of the two constituents were between 130 and 200 μg/ml. Scanning electron microscopy results demonstrated that the essential oil inhibited biofilm formation and altered its architecture. Survival curves indicated that the essential oil led to a reduction in the viability of different bacteria. The essential oil also induced significant leakage of potassium ions from S. pyogenes. The essential oil (100 μg/mouse) and grandisol (135 μg/mouse) significantly reduced the number of viable bacterial cells in the lungs (P<0.01). However, intake of 100 μg/mouse of essential oil or grandisol 135 μg/mouse once or twice each day for 9 days did not produce any toxic effects in the mice. In conclusion, the in vitro and in vivo results suggested that the essential oil of A. vestita and one of its major constituents, grandisol, can significantly

  6. Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.

    Science.gov (United States)

    Popp, Felix C; Popp, Marie Christine; Zhao, Yue; Betzler, Christopher; Kropf, Siegfried; Garlipp, Benjamin; Benckert, Christoph; Kalinski, Thomas; Lippert, Hans; Bruns, Christiane J

    2017-03-29

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection. Patients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread. Pancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy. Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the

  7. Investigation of the neuroprotective effects of bee-venom acupuncture in a mouse model of Parkinson's disease by using immunohistochemistry and In-vivo 1H magnetic resonance spectroscopy at 9.4 T

    Science.gov (United States)

    Yoon, Moon-Hyun; Lee, Do-Wan; Kim, Hyun-Jin; Chung, Jin-Yeung; Doo, Ah-Reum; Park, Hi-Joon; Kim, Seung-Nam; Choe, Bo-Young

    2013-01-01

    Neuroprotective therapeutics slows down the degeneration process in animal models of Parkinson's disease (PD). The neuronal survival in PD animal models is often measured by using immunohistochemistry. However, dynamic changes in the pathology of the brain cannot be explored with this technique. Application of in-vivo 1H magnetic resonance spectroscopy (1H MRS) can cover this shortcoming, as these techniques are non-invasive and can be repeated over time in the same animal. Thus, the sensitivity of both techniques to measure changes in the PD pathology was explored in an experiment studying the neuroprotective effects of the vigilance enhancer bee-venom (BV) in a mouse model of PD. The mice were pre-treated with 0.02-ml BV administered to the acupuncture point GB34 (Yangneungcheon) once every 3 days for 2 weeks. Three groups were classified as control, MPTP-intoxicated PD model and BV-treated mice. Outer volume suppression combined with the ultra-short echo-time STEAM (TE = 2.2 ms, TM = 20 ms, TR = 5000 ms) was used for localized in-vivo 1H MRS. Based on the 1H MRS spectral analysis, substantial changes of the neurochemical profiles were evaluated in the three investigated groups. In particular, the glutamate complex (Glx)/creatine (Cr) ratio (7.72 ± 1.25) in the PD group was significantly increased compared to that in the control group (3.93 ± 2.21, P = 0.001). Compared to the baseline values, the Glx/Cr ratio of the BV-treated group was significantly decreased 2 weeks after MPTP intoxication (one-way ANOVA, p acupuncture in a mouse model of PD could be quantified by using immunohistochemistry and 1H MRS.

  8. The value of a rapid contrast-enhanced angio-MRI protocol in the detection of head and neck paragangliomas in SDHx mutations carriers: a retrospective study on behalf of the PGL.EVA investigators*

    Energy Technology Data Exchange (ETDEWEB)

    Gravel, Guillaume; Hernigou, Anne [Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Service de Radiologie, Paris (France); Niccoli, Patricia [Centre Hospitalier Universitaire la Timone, Assistance Publique-Hopitaux de Marseille, Service d' Endocrinologie, Diabete et Maladies Metaboliques, Marseille (France); Rohmer, Vincent [Centre Hospitalier Universitaire d' Angers, Service d' Endocrinologie, Diabetologie, Nutrition, Angers (France); LUNAM Universite, INSERM, U1063, Angers (France); Moulin, Guy [Centre Hospitalier Universitaire la Timone, Assistance Publique-Hopitaux de Marseille, Service de Radiologie, Marseille (France); Borson-Chazot, Francoise [Federation d' Endocrinologie, Hospices civils de Lyon, Groupement Hospitalier Est, Lyon (France); Universite de Lyon, Faculte de Medecine Lyon-Est, Lyon (France); Cancer Research Center of Lyon, INSERM UMR1052, UMR CNRS 5286, Lyon (France); Rousset, Pascal [Hospices civils de Lyon, Groupement Hospitalier Est, Service de Radiologie, Lyon (France); Pasco-Papon, Anne [Centre Hospitalier Universitaire d' Angers, Service de Radiologie, Angers (France); Marcus, Claude [Centre Hospitalo-Universitaire de Reims, Service de Radiologie, Reims (France); Dubrulle, Frederique [Centre Hospitalo-Universitaire de Lille, Service de Radiologie, Lille (France); Gouya, Herve [Hopital Cochin, Assistance Publique-Hopitaux de Paris, Service de Radiologie, Paris (France); Bidault, Francois [Institut Gustave Roussy, Service de Radiologie, Villejuif (France); Dupas, Benoit [Centre Hospitalo-Universitaire de Nantes, Service de Radiologie, Nantes (France); Gabrillargues, Jean [Centre Hospitalo-Universitaire de Clermont-Ferrand, Service de Neuroradiologie, Clermont Ferrand (France); Caumont-Prim, Aurore [Unite d' Epidemiologie et de Recherche Clinique, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris (France); Centre d' investigation Epidemiologique 4, INSERM, Paris (France); Gimenez-Roqueplo, Anne-Paule [Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Service de Genetique, Paris (France); Paris Cardiovascular Research Center, INSERM, UMR970, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Halimi, Philippe [Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Service de Radiologie, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France)

    2016-06-15

    To assess the performance of a simplified MRI protocol consisting of a contrast-enhanced three-dimensional MR angiography (CE-MRA) in association with a post-contrast T1-weighted sequence (T1WIV) for the detection of HNPGLs in SDHx mutation carriers. This retrospective sub-study is based on the multicenter PGL.EVA cohort, which prospectively enrolled SDHx mutation carriers from 2005 to 2009; 157 index cases or relatives were included. CE-MRA and the T1WIV images were read solely with knowledge of the clinical data but blind to the diagnosis. Sensitivity, specificity and likelihood ratios for the simplified MRI protocol were compared to the full MRI protocol reading results and to the gold standard status obtained through the consensus of an expert committee. The sensitivity and specificity of the readings of the simplified MRI protocol were, respectively, 88.7 % (95 % CI = 78.1-95.3) and 93.7 % (95 % CI = 86.8-97.7) versus 80.7 % (95 % CI = 68.6-89.6) and 94.7 % (95 % CI = 88.1-98.3) for the readings of the full MRI protocol. The simplified post-contrast MRI with shorter duration (5 to 10 minutes) showed no performance difference compared to the lengthy standard full MRI and can be proposed for the detection of head and neck paragangliomas (HNPGLs) in SDHx mutation carriers. (orig.)

  9. In vitro/in vivo investigations to examine the gender differences in the pharmacokinetics of novel oral Janus kinase (JAK) inhibitor ASP015K and sulfate metabolite M2 in rats.

    Science.gov (United States)

    Oda, Kazuo; Nakada, Naoyuki; Nagasaka, Yasuhisa

    2015-01-01

    1. Although marked gender differences have been reported for the exposure level of the sulfate metabolite M2 of ASP015K in rats, no such differences have been reported for the unchanged drug. To clarify the cause of these pharmacokinetic gender differences, we investigated the in vitro hepatic sulfation, glucuronidation, and cytochrome P450 (CYP) metabolism of ASP015K in rat liver cytosols or rat liver microsomes. Further, in vivo excretion and metabolic profiles were investigated using rat urine, bile, and feces post-ASP015K administration. 2. In vitro metabolism study using liver cytosols clearly suggested that the gender differences in the M2 exposure were mainly attributed to the female-predominant ASP015K metabolism mediated by sulfotransferase (SULT). Metabolic profiles in urine and bile from male rats suggested that the major elimination pathway of ASP015K is glucuronidation in rats. No remarkable gender differences in the in vitro glucuronidation were observed. 3. The contribution of the sulfation pathway to the clearance of ASP015K was markedly lower than that of the glucuronidation pathway in both male and female rats. These results might explain why gender differences were not marked for ASP015K exposure but were for M2.

  10. Study Protocol – Improving Access to Kidney Transplants (IMPAKT: A detailed account of a qualitative study investigating barriers to transplant for Australian Indigenous people with end-stage kidney disease

    Directory of Open Access Journals (Sweden)

    Anderson Kate

    2008-02-01

    Full Text Available Abstract Background Indigenous Australians are slightly more than 2% of the total Australian population however, in recent years they have comprised between 6 and 10% of new patients beginning treatment for end-stage kidney disease (ESKD. Although transplant is considered the optimal form of treatment for many ESKD patients there is a pronounced disparity between the rates at which Indigenous ESKD patients receive transplants compared with their non-Indigenous counterparts. The IMPAKT (Improving Access to Kidney Transplants Interview study investigated reasons for this disparity through a large scale, in-depth interview study involving patients, nephrologists and key decision-making staff at selected Australian transplant and dialysis sites. Methods The design and conduct of the study reflected the multi-disciplinary membership of the core IMPAKT team. Promoting a participatory ethos, IMPAKT established partnerships with a network of hospital transplant units and hospital dialysis treatment centres that provide treatment to the vast majority of Indigenous patients across Australia. Under their auspices, the IMPAKT team conducted in-depth interviews in 26 treatment/service centres located in metropolitan, regional and remote Australia. Peer interviewing supported the engagement of Indigenous patients (146, and nephrologists (19. In total IMPAKT spoke with Indigenous and non-Indigenous patients (241, key renal nursing and other (non-specialist staff (95 and a small number of relevant others (28. Data analysis was supported by QSR software. At each site, IMPAKT also documented educational programs and resources, mapped an hypothetical ‘patient journey’ to transplant through the local system and observed patient care and treatment routines. Discussion The national scope, inter-disciplinary approach and use of qualitative methods in an investigation of a significant health inequality affecting Indigenous people is, we believe, an Australian first

  11. Transmission Control Protocol, DARPA Internet Program Protocol Specification

    Science.gov (United States)

    1981-09-01

    particular a source or destination of messages from the point of view of the communicatio network. identification An Internet Protocol field. This...15-( RFC- 793 "* •TRANSMISSION CONTROL PROTOCOL ’-v DARPA INTERNET PROGRAM PROTOCOL SPECIFICATION September 1981 S... INTERNET PROGRAM PROTOCOL SPECIFICATION 1. INTRODUCTION The Transmission Control Protocol (TCP) is intended for use as a highly reliable host-to-host

  12. In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

    Science.gov (United States)

    Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

    2015-01-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. PMID:18241900

  13. In vivo MRI quantification of individual muscle and organ volumes for assessment of anabolic steroid growth effects.

    Science.gov (United States)

    Wu, Ed X; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B; Vasselli, Joseph R

    2008-04-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 T scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R=0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions.

  14. Physiological comparability of the harmonized INFOGEST in vitro digestion method to in vivo pig digestion.

    Science.gov (United States)

    Egger, Lotti; Schlegel, Patrick; Baumann, Christian; Stoffers, Helena; Guggisberg, Dominik; Brügger, Cédric; Dürr, Desirée; Stoll, Peter; Vergères, Guy; Portmann, Reto

    2017-12-01

    Recently, a static in vitro digestion (IVD) protocol was published by Minekus and coworkers (Minekus et al., 2014) within the COST INFOGEST network. The protocol, concentrating on physiological enzyme activities had the main goal to improve the comparability of experimental data between labs. The protocol was validated in several inter-laboratory studies using skim milk powder (SMP) and indeed demonstrated improved harmonization compared with previous experiments with individual IVD protocols (Egger et al., 2016). Although the enzyme activities and salt concentrations of the harmonized protocol are based on available human in vivo data, confirmation of the protocol's physiological relevance has been lacking until now. The main goal of the study was therefore to compare the harmonized IVD protocol with data from in vivo digestion. Towards this aim, an in vivo pig experiment with the same SMP as used for the validation of the IVD protocol was performed followed by a comparison of protein hydrolysis between in vivo and in vitro results. Protein hydrolysis at different levels was analyzed with gel electrophoresis, mass spectrometry, high performance liquid chromatography, and spectrophotometric o-phthaldialdehyde determination of free amino acids. Principle component analysis was used for graphical data comparison. Milk proteins detected after gastric IVD corresponded to gastric and duodenal in vivo samples and intestinal IVD samples corresponded to distal jejunal in vivo samples. Peptides identified after the gastric phase of IVD, correlated with in vivo gastric samples (r=0.8) and intestinal IVD peptides correlated best with in vivo samples collected from the median jejunum (r=0.57). Free amino acids were in both systems mainly released during the intestinal phase of digestion. Protein hydrolysis in the harmonized IVD was similar to in vivo protein hydrolysis in pigs at the gastric and intestinal endpoints. Therefore, the harmonized static in vitro protocol is suited

  15. Comparison of two in vivo and two ex vivo tests to assess the antibacterial activity of several antiseptics.

    Science.gov (United States)

    Messager, S; Goddard, P A; Dettmar, P W; Maillard, J-Y

    2004-10-01

    An ex vivo test was adapted to mimic the in vivo conditions of testing antiseptic activity on human forearms and in the European Standard Hygienic Handwash Test (BSEN 1499). The study was to validate the ex vivo protocols using 4.8% (w/v) para-chloro-meta-xylenol (PCMX, neat Dettol), 0.5% (w/v) triclosan in 70% (v/v) isopropanol, and 2% (v/v) povidone-iodine against a high bacterial inoculum (>10(8) cfu/mL) of Escherichia coli NCTC 10538. Two ex vivo tests using human skin samples, including one introducing a mechanical rubbing effect, were compared with two corresponding in vivo tests (the forearm test and the BSEN handwashing test). All antiseptics assessed in vivo (forearm and handwash tests) produced reductions in bacterial counts that were significantly greater than those for the non-medicated soft soap control. When assessed ex vivo without rubbing, only PCMX and povidone-iodine achieved reductions significantly greater than soft soap. When assessed ex vivo with mechanical rubbing, only PCMX and triclosan achieved reductions significantly greater than soft soap. Overall, the antiseptics at the concentrations tested were more active when tested in vivo than ex vivo. The addition of a mechanical effect, either in vivo by the volunteers washing their hands or ex vivo by a drill rubbing two skin samples against each other, produced a significantly greater reduction in bacterial concentrations. The ex vivo tests were easily adapted to mimic in vivo protocols. The value of such tests, particularly the one that includes a rubbing effect, may be significant as they avoid the need for human volunteers.

  16. A study protocol of a randomised controlled trial incorporating a health economic analysis to investigate if additional allied health services for rehabilitation reduce length of stay without compromising patient outcomes

    Directory of Open Access Journals (Sweden)

    Peiris Casey

    2010-11-01

    Full Text Available Abstract Background Reducing patient length of stay is a high priority for health service providers. Preliminary information suggests additional Saturday rehabilitation services could reduce the time a patient stays in hospital by three days. This large trial will examine if providing additional physiotherapy and occupational therapy services on a Saturday reduces health care costs, and improves the health of hospital inpatients receiving rehabilitation compared to the usual Monday to Friday service. We will also investigate the cost effectiveness and patient outcomes of such a service. Methods/Design A randomised controlled trial will evaluate the effect of providing additional physiotherapy and occupational therapy for rehabilitation. Seven hundred and twelve patients receiving inpatient rehabilitation at two metropolitan sites will be randomly allocated to the intervention group or control group. The control group will receive usual care physiotherapy and occupational therapy from Monday to Friday while the intervention group will receive the same amount of rehabilitation as the control group Monday to Friday plus a full physiotherapy and occupational therapy service on Saturday. The primary outcomes will be patient length of stay, quality of life (EuroQol questionnaire, the Functional Independence Measure (FIM, and health utilization and cost data. Secondary outcomes will assess clinical outcomes relevant to the goals of therapy: the 10 metre walk test, the timed up and go test, the Personal Care Participation Assessment and Resource Tool (PC PART, and the modified motor assessment scale. Blinded assessors will assess outcomes at admission and discharge, and follow up data on quality of life, function and health care costs will be collected at 6 and 12 months after discharge. Between group differences will be analysed with analysis of covariance using baseline measures as the covariate. A health economic analysis will be carried out

  17. From protocol to published report

    DEFF Research Database (Denmark)

    Berendt, Louise; Callréus, Torbjörn; Petersen, Lene Grejs

    2016-01-01

    BACKGROUND: Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols...... and published reports of academic clinical drug trials. METHODS: A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory......), primary objective, primary endpoint, and--for confirmatory trials only--hypothesis and sample size calculation. We used logistic regression, χ(2), and Fisher's exact test. RESULTS: A total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority...

  18. In vivo

    Science.gov (United States)

    Kim, Michele M; Penjweini, Rozhin; Zhu, Timothy C

    2015-03-02

    Macroscopic modeling of the apparent reacted singlet oxygen concentration ([ 1 O 2 ] rx ) for use with photodynamic therapy (PDT) has been developed and studied for benzoporphryin derivative monoacid ring A (BPD), a common photosensitizer. The four photophysical parameters (ξ, σ, β, δ) and threshold singlet oxygen dose ([ 1 O 2 ] rx,sh ) have been investigated and determined using the RIF model of murine fibrosarcomas and interstitial treatment delivery. These parameters are examined and verified further by monitoring tumor growth post-PDT. BPD was administered at 1 mg/kg, and mice were treated 3 hours later with fluence rates ranging between 75 - 150 mW/cm 2 and total fluences of 100 - 350 J/cm 2 . Treatment was delivered superficially using a collimated beam. Changes in tumor volume were tracked following treatment. The tumor growth rate was fitted for each treatment condition group and compared using dose metrics including total light dose, PDT dose, and reacted singlet oxygen. Initial data showing the correlation between outcomes and various dose metrics indicate that reacted singlet oxygen serves as a good dosimetric quantity for predicting PDT outcome.

  19. ATM and Internet protocol

    CERN Document Server

    Bentall, M; Turton, B

    1998-01-01

    Asynchronous Transfer Mode (ATM) is a protocol that allows data, sound and video being transferred between independent networks via ISDN links to be supplied to, and interpreted by, the various system protocols.ATM and Internet Protocol explains the working of the ATM and B-ISDN network for readers with a basic understanding of telecommunications. It provides a handy reference to everyone working with ATM who may not require the full standards in detail, but need a comprehensive guide to ATM. A substantial section is devoted to the problems of running IP over ATM and there is some discussion o

  20. Linear Logical Voting Protocols

    DEFF Research Database (Denmark)

    DeYoung, Henry; Schürmann, Carsten

    2012-01-01

    Current approaches to electronic implementations of voting protocols involve translating legal text to source code of an imperative programming language. Because the gap between legal text and source code is very large, it is difficult to trust that the program meets its legal specification....... In response, we promote linear logic as a high-level language for both specifying and implementing voting protocols. Our linear logical specifications of the single-winner first-past-the-post (SW- FPTP) and single transferable vote (STV) protocols demonstrate that this approach leads to concise...

  1. Playing With Population Protocols

    Directory of Open Access Journals (Sweden)

    Xavier Koegler

    2009-06-01

    Full Text Available Population protocols have been introduced as a model of sensor networks consisting of very limited mobile agents with no control over their own movement: A collection of anonymous agents, modeled by finite automata, interact in pairs according to some rules. Predicates on the initial configurations that can be computed by such protocols have been characterized under several hypotheses. We discuss here whether and when the rules of interactions between agents can be seen as a game from game theory. We do so by discussing several basic protocols.

  2. A streamlined ribosome profiling protocol for the characterization of microorganisms

    DEFF Research Database (Denmark)

    Latif, Haythem; Szubin, Richard; Tan, Justin

    2015-01-01

    Ribosome profiling is a powerful tool for characterizing in vivo protein translation at the genome scale, with multiple applications ranging from detailed molecular mechanisms to systems-level predictive modeling. Though highly effective, this intricate technique has yet to become widely used...... fraction of informative reads, all while retaining the high quality standards of the existing protocol....

  3. USA-USSR protocol

    CERN Multimedia

    1970-01-01

    On 30 November the USA Atomic Energy Commission and the USSR State Committee for the Utilization of Atomic Energy signed, in Washington, a protocol 'on carrying out of joint projects in the field of high energy physics at the accelerators of the National Accelerator Laboratory (Batavia) and the Institute for High Energy Physics (Serpukhov)'. The protocol will be in force for five years and can be extended by mutual agreement.

  4. A Fatigue Measuring Protocol for Wireless Body Area Sensor Networks.

    Science.gov (United States)

    Akram, Sana; Javaid, Nadeem; Ahmad, Ashfaq; Khan, Zahoor Ali; Imran, Muhammad; Guizani, Mohsen; Hayat, Amir; Ilahi, Manzoor

    2015-12-01

    As players and soldiers preform strenuous exercises and do difficult and tiring duties, they are usually the common victims of muscular fatigue. Keeping this in mind, we propose FAtigue MEasurement (FAME) protocol for soccer players and soldiers using in-vivo sensors for Wireless Body Area Sensor Networks (WBASNs). In FAME, we introduce a composite parameter for fatigue measurement by setting a threshold level for each sensor. Whenever, any sensed data exceeds its threshold level, the players or soldiers are declared to be in a state of fatigue. Moreover, we use a vibration pad for the relaxation of fatigued muscles, and then utilize the vibrational energy by means of vibration detection circuit to recharge the in-vivo sensors. The induction circuit achieves about 68 % link efficiency. Simulation results show better performance of the proposed FAME protocol, in the chosen scenarios, as compared to an existing Wireless Soccer Team Monitoring (WSTM) protocol in terms of the selected metrics.

  5. Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees

    Science.gov (United States)

    Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

    2016-01-01

    A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. PMID:26811365

  6. Investigating the application of motion accelerometers as a sleep monitoring technique and the clinical burden of the intensive care environment on sleep quality: study protocol for a prospective observational study in Australia.

    Science.gov (United States)

    Delaney, Lori J; Currie, Marian J; Huang, Hsin-Chia Carol; Litton, Edward; Wibrow, Bradley; Lopez, Violeta; Haren, Frank Van

    2018-01-21

    prehospital discharge survey regarding patients' perception of sleep quality and disturbing factors using the Little Sleep Questionnaire will be undertaken. Associations between sleep disturbance, noise and light levels, and the frequency of clinical interactions will also be investigated. Sound and luminance levels will be recorded at 1 s epochs via Extech SDL600 and SDL400 monitoring devices. Clinical interactions will be logged via the electronic patient record system Metavision which documents patient monitoring and clinical care. The relevant institutions have approved the study protocol and consent procedures. The findings of the study will contribute to the understanding of sleep disturbance, and the ability to implement sleep monitoring methods within ICUs. Understanding the contribution of a clinical environment on sleep disturbance may provide insight into the need to address clinical environmental issues that may positively influence patient outcomes, and could dispel notions that the environment is a primary factor in sleep disturbance. The research findings will be disseminated via presentations at national and international conferences, proceedings and published articles in peer-reviewed journals. ACTRN12615000945527; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Abortamento recorrente de causa imunológica: avaliação de um protocolo de investigação e tratamento Recurrent abortion due to immunologic causes: evaluation of an investigation and treatment protocol

    Directory of Open Access Journals (Sweden)

    Ricardo Barini

    1998-03-01

    Full Text Available São apresentados resultados de protocolo de investigação diagnóstica e tratamento do aborto recorrente de causa imunológica. Estima-se que até 60 % das pacientes que não apresentam nenhuma alteração clínica identificável sejam portadoras de perturbações aloimunes associadas ao aborto Uma das alternativas terapêuticas é a imunização com linfócitos do parceiro. Foram revisados os resultados de 116 pacientes seguidas no Departamento de Tocoginecologia da UNICAMP. As mulheres foram avaliadas segundo minucioso protocolo de investigação das causas de aborto recorrente conhecidas (genética, hormonal, uterina e infecciosa, imunológicos auto-imunes (síndrome do anticorpo antifosfolipídico, auto-anticorpos anômalos e aloimunes (prova cruzada por microlinfocitotoxicidade e cultura mista de linfócitos. As que apresentavam prova cruzada negativa e índice de inibição menor que 50% na cultura mista de linfócitos foram tratadas com duas imunizações intradérmicas de concentrado de linfócitos de seus maridos. Foram estimuladas a engravidar se os exames de controle demonstrassem prova cruzada positiva e cultura mista com inibição superior a 50%. Quando este regime não resultou em mudança significativa foram tratadas novamente com concentrado de linfócitos de seus maridos, associado ou não a um doador não-aparentado. Com esta abordagem terapêutica 81% tiveram evolução gestacional favorável .Results on investigation and immune treatment for recurrent abortion are presented. Up to 60% of patients who are free of any clinical identifiable cause for abortion are believed to have alloimmune abnormalities. One of the suggested therapies for this condition is paternal lymphocyte immunization. We present the result of 116 pregnancies followed at the Departamento de Tocoginecologia UNICAMP. Patients were thoroughly evaluated for causes of recurrent abortion mentioned in the literature (genetics, hormones, uterine abnormalities

  8. In vivo genotoxic effects of dietary heme iron on rat colon mucosa and ex vivo effects on colon cells monitored by an optimized alkaline comet assay.

    Directory of Open Access Journals (Sweden)

    Océane, C Martin

    2015-04-01

    In conclusion, our results offer a suitable protocol to evaluate genotoxicity on in vivo cryopreserved colon mucosa and on in vitro murine colonic cells, with a middle throughput capacity. This protocol confirms the increase of genotoxicity in rat colon mucosa after an heme-iron diet. Moreover, this protocol enables the demonstration that aldehydes from heme-induced lipoperoxidation are responsible for this increase of genotoxicity.

  9. Timed Analysis of Security Protocols

    NARCIS (Netherlands)

    Corin, R.J.; Etalle, Sandro; Hartel, Pieter H.; Mader, Angelika H.

    We propose a method for engineering security protocols that are aware of timing aspects. We study a simplified version of the well-known Needham Schroeder protocol and the complete Yahalom protocol, where timing information allows the study of different attack scenarios. We model check the protocols

  10. Timed Analysis of Security Protocols

    NARCIS (Netherlands)

    Corin, R.J.; Etalle, Sandro; Hartel, Pieter H.; Mader, Angelika H.

    2007-01-01

    We propose a method for engineering security protocols that are aware of timing aspects. We study a simplified version of the well-known Needham Schroeder protocol and the complete Yahalom protocol, where timing information allows the study of different attack scenarios. We model check the protocols

  11. In vivo introduction of transgenes into mouse sciatic nerve cells in situ using viral vectors.

    Science.gov (United States)

    Gonzalez, Sergio; Fernando, Ruani N; Perrin-Tricaud, Claire; Tricaud, Nicolas

    2014-05-01

    The myelin sheath is essential for the rapid and efficient propagation of action potentials. However, our understanding of the basic molecular mechanisms that regulate myelination, demyelination and remyelination is limited. Schwann cells produce myelin in the peripheral nervous system and remain associated with the axons of peripheral neurons throughout axonal migration to the target. Owing to the intimate relationship between these cell types it is difficult to fully reproduce their function in vitro. For this reason, we developed an approach based on the injection of an engineered virus into the sciatic nerve of mice to locally transduce peripheral nerve cells. This approach can be used as an alternative to germline transgenesis to facilitate the investigation of peripheral nerve biology in vivo. The detailed protocol, described here, requires 3 weeks to complete. In comparison with genetic modification strategies, this protocol is a fast, reproducible and straightforward method for introducing exogenous factors into myelinating Schwann cells and myelinated axons in vivo to investigate specific molecular mechanisms.

  12. Magnesium alloys: predicting in vivo corrosion with in vitro immersion testing.

    Science.gov (United States)

    Walker, Jemimah; Shadanbaz, Shaylin; Kirkland, Nicholas T; Stace, Edward; Woodfield, Tim; Staiger, Mark P; Dias, George J

    2012-05-01

    Magnesium (Mg) and its alloys have been proposed as degradable replacements to commonly used orthopedic biomaterials such as titanium alloys and stainless steel. However, the corrosion of Mg in a physiological environment remains a difficult characteristic to accurately assess with in vitro methods. The aim of this study was to identify a simple in vitro immersion test that could provide corrosion rates similar to those observed in vivo. Pure Mg and five alloys (AZ31, Mg-0.8Ca, Mg-1Zn, Mg-1Mn, Mg-1.34Ca-3Zn) were immersed in either Earle's balanced salt solution (EBSS), minimum essential medium (MEM), or MEM-containing 40 g/L bovine serum albumin (MEMp) for 7, 14, or 21 days before removal and assessment of corrosion by weight loss. This in vitro data was compared to in vivo corrosion rates of the same materials implanted in a subcutaneous environment in Lewis rats for equivalent time points. The results suggested that, for the alloys investigated, the EBSS buffered with sodium bicarbonate provides a rate of degradation comparable to those observed in vivo. In contrast, the addition of components such as (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES), vitamins, amino acids, and albumin significantly increased corrosion rates. Based on these findings, it is proposed that with this in vitro protocol, immersion of Mg alloys in EBSS can be used as a predictor of in vivo corrosion. Copyright © 2012 Wiley Periodicals, Inc.

  13. Vertical Protocol Composition

    DEFF Research Database (Denmark)

    Groß, Thomas; Mödersheim, Sebastian Alexander

    2011-01-01

    composition, and it is truly commonplace in today’s communication with the diversity of VPNs and secure browser sessions. In fact, it is normal that we have several layers of secure channels: For instance, on top of a VPN-connection, a browser may establish another secure channel (possibly with a different...... end point). Even using the same protocol several times in such a stack of channels is not unusual: An application may very well establish another TLS channel over an established one. We call this selfcomposition. In fact, there is nothing that tells us that all these compositions are sound, i.......e., that the combination cannot introduce attacks that the individual protocols in isolation do not have. In this work, we prove a composability result in the symbolic model that allows for arbitrary vertical composition (including self-composition). It holds for protocols from any suite of channel and application...

  14. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...

  15. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  16. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including......In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  17. Ex-vivo MR Volumetry of Human Brain Hemispheres

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

    2013-01-01

    Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

  18. Comparison of ex vivo and in vivo micro-computed tomography of rat tibia at different scanning settings.

    Science.gov (United States)

    Longo, Amanda B; Salmon, Phil L; Ward, Wendy E

    2017-08-01

    The parameters of a micro-computed tomography (μCT) scan, including whether a bone is imaged in vivo or ex vivo, determine the quality of the resulting image. In turn, this impacts the accuracy of the trabecular and cortical outcomes. The absolute impact of μCT scanning at different voxel sizes and whether the sample is imaged in vivo or ex vivo on the morphological outcomes of the proximal tibia in the rat is unknown. The right proximal tibia of 6-month-old Sham-control and ovariectomized (OVX) rats (n = 8/group) was scanned using μCT (SkyScan 1176, Bruker, Kontich, Belgium) using three sets of parameters (9 μm ex vivo, 18 μm ex vivo, 18 μm in vivo) to compare the trabecular and cortical outcomes. Regardless of scan protocols, differences between Sham and OVX groups were observed as expected. At a voxel size of 18 μm, scanning in vivo or ex vivo had no effect on any of the outcomes measured. However, compared to a 9 μm voxel size scan, imaging at 18 μm resulted in significant underestimation of the connectivity density (p vivo scanning. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1690-1698, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. The Master Protocol Concept.

    Science.gov (United States)

    Redman, Mary W; Allegra, Carmen J

    2015-10-01

    During the past decade, biomedical technologies have undergone an explosive evolution-from the publication of the first complete human genome in 2003, after more than a decade of effort and at a cost of hundreds of millions of dollars-to the present time, where a complete genomic sequence can be available in less than a day and at a small fraction of the cost of the original sequence. The widespread availability of next-generation genomic sequencing has opened the door to the development of precision oncology. The need to test multiple new targeted agents both alone and in combination with other targeted therapies, as well as classic cytotoxic agents, demands the development of novel therapeutic platforms (particularly Master Protocols) capable of efficiently and effectively testing multiple targeted agents or targeted therapeutic strategies in relatively small patient subpopulations. Here, we describe the Master Protocol concept, with a focus on the expected gains and complexities of the use of this design. An overview of Master Protocols currently active or in development is provided along with a more extensive discussion of the Lung Master Protocol (Lung-MAP study). Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Principles of Protocol Design

    DEFF Research Database (Denmark)

    Sharp, Robin

    This is a new and updated edition of a book first published in 1994. The book introduces the reader to the principles used in the construction of a large range of modern data communication protocols, as used in distributed computer systems of all kinds. The approach taken is rather a formal one...

  1. Frameworks for Protocol Implementation

    NARCIS (Netherlands)

    de Barros Barbosa, Ciro; de barros Barbosa, C.; Ferreira Pires, Luis; Pires, L.F.; van Sinderen, Marten J.

    1998-01-01

    This paper reports on the development of a catalogue of frameworks for protocol implementation. Frameworks are software structures developed for a specific application domain, which can be re-used in the implementation of various different concrete systems in this domain. By using frameworks we aim

  2. Clothing Longevity Protocol: final

    OpenAIRE

    Cooper, T.; Claxton, S; Hill, H; Holbrook, K; Hughes, M.; Knox, A.; Oxborrow, L; Nottingham Trent University

    2014-01-01

    The Clothing Longevity Protocol offers guidelines for good practice in order to aid moves towards garments that will last longer and thus to help protect brand value, screen out garments which fail prematurely and reduce the environmental impact of the clothing sector.

  3. Critical Response Protocol

    Science.gov (United States)

    Ellingson, Charlene; Roehrig, Gillian; Bakkum, Kris; Dubinsky, Janet M.

    2016-01-01

    This article introduces the Critical Response Protocol (CRP), an arts-based technique that engages students in equitable critical discourse and aligns with the "Next Generation Science Standards" vision for providing students opportunities for language learning while advancing science learning (NGSS Lead States 2013). CRP helps teachers…

  4. Detection of Helicobacter pylori in the Gastric Mucosa by Fluorescence In Vivo Hybridization

    DEFF Research Database (Denmark)

    Fontenete, Silvia; Leite, Marina; Figueiredo, Céu

    2017-01-01

    In this chapter, we describe a fluorescence in vivo hybridization (FIVH) protocol, using nucleic acid probes, for the detection of the bacterium Helicobacter pylori in the gastric mucosa of an infected C57BL/6 mouse model. This protocol should be easily extended to other microorganisms not only...

  5. Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol.

    Science.gov (United States)

    Arndtz, Katherine; Corrigan, Margaret; Rowe, Anna; Kirkham, Amanda; Barton, Darren; Fox, Richard P; Llewellyn, Laura; Athwal, Amrita; Wilkhu, Manpreet; Chen, Yung-Yi; Weston, Chris; Desai, Amisha; Adams, David H; Hirschfield, Gideon M

    2017-07-03

    Primary sclerosing cholangitis (PSC) is a progressive inflammatory liver disease characterised by relentless liver fibrosis and a high unmet need for new therapies. Preventing fibrosis represents an important area of interest in the development of vital new drugs. Vascular adhesion protein-1 (VAP-1) drives inflammation in liver disease, and provision of an antibody against VAP-1 blunts fibrosis in murine models of liver injury. BUTEO is a single-arm, two-stage, open-label, multi-centre, phase II clinical trial. Up to 59 patients will receive treatment with anti-VAP monoclonal antibody, BTT1023, over a 78-day treatment period. Adults with PSC and a serum alkaline phosphatase (ALP) of at least 1.5 times the upper limit of normal will be included. Our primary outcome measure is a reduction in ALP by >25% from baseline to Day 99. Secondary outcome measures include safety and tolerability, changes pre therapy/post therapy in circulating serum VAP-1 as well as imaging findings. The first patient participant was recruited on 08 September 2015. This protocol has been approved by the Research Ethics Committee (REC, reference 14/EM/1272). The first REC approval date was 06 January 2015 with three subsequent approved amendments. This article refers to protocol V3.0, dated 16 March 2016. Results will be disseminated via peer-reviewed publication and presentation at international conferences. The trial is registered with the European Medicines agency (EudraCT: 2014-002393-37), the National Institute for Health Research (Portfolio ID: 18051) and ISRCTN: 11233255. The clinicaltrials.gov identifier is NCT02239211. Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Satellite Communications Using Commercial Protocols

    Science.gov (United States)

    Ivancic, William D.; Griner, James H.; Dimond, Robert; Frantz, Brian D.; Kachmar, Brian; Shell, Dan

    2000-01-01

    NASA Glenn Research Center has been working with industry, academia, and other government agencies in assessing commercial communications protocols for satellite and space-based applications. In addition, NASA Glenn has been developing and advocating new satellite-friendly modifications to existing communications protocol standards. This paper summarizes recent research into the applicability of various commercial standard protocols for use over satellite and space- based communications networks as well as expectations for future protocol development. It serves as a reference point from which the detailed work can be readily accessed. Areas that will be addressed include asynchronous-transfer-mode quality of service; completed and ongoing work of the Internet Engineering Task Force; data-link-layer protocol development for unidirectional link routing; and protocols for aeronautical applications, including mobile Internet protocol routing for wireless/mobile hosts and the aeronautical telecommunications network protocol.

  7. In vivo administration of dental epithelial stem cells at the apical end of the mouse incisor

    Directory of Open Access Journals (Sweden)

    Giovanna eOrsini

    2015-04-01

    Full Text Available Cell-based tissue regeneration is an attractive approach that complements traditional surgical techniques for replacement of injured and lost tissues. The continuously growing rodent incisor provides an excellent model system for investigating cellular and molecular mechanisms that underlie tooth renewal and regeneration. An active population of dental epithelial progenitor/stem cells located at the posterior part of the incisor, commonly called cervical loop area, ensures the continuous supply of cells that are responsible for the secretion of enamel matrix. To explore the potential of these epithelial cells in therapeutic approaches dealing with enamel defects, we have developed a new method for their in vivo administration in the posterior part of the incisor. Here we provide the step-by-step protocol for the isolation of dental epithelial stem cells and their delivery at targeted areas of the jaw. This simple and yet powerful protocol, consisting in drilling a hole in the mandibular bone, in close proximity to the cervical loop area of the incisor, followed up by injection of stem cells, is feasible, reliable, and effective. This in vivo approach opens new horizons and possibilities for cellular therapies involving pathological and injured dental tissues.

  8. Symmetric cryptographic protocols

    CERN Document Server

    Ramkumar, Mahalingam

    2014-01-01

    This book focuses on protocols and constructions that make good use of symmetric pseudo random functions (PRF) like block ciphers and hash functions - the building blocks for symmetric cryptography. Readers will benefit from detailed discussion of several strategies for utilizing symmetric PRFs. Coverage includes various key distribution strategies for unicast, broadcast and multicast security, and strategies for constructing efficient digests of dynamic databases using binary hash trees.   •        Provides detailed coverage of symmetric key protocols •        Describes various applications of symmetric building blocks •        Includes strategies for constructing compact and efficient digests of dynamic databases

  9. Unconditionally Secure Protocols

    DEFF Research Database (Denmark)

    Meldgaard, Sigurd Torkel

    This thesis contains research on the theory of secure multi-party computation (MPC). Especially information theoretically (as opposed to computationally) secure protocols. It contains results from two main lines of work. One line on Information Theoretically Secure Oblivious RAMS, and how...... they are used to speed up secure computation. An Oblivious RAM is a construction for a client with a small $O(1)$ internal memory to store $N$ pieces of data on a server while revealing nothing more than the size of the memory $N$, and the number of accesses. This specifically includes hiding the access pattern...... the bottleneck of sorting networks. And we show how to utilize this construction for four-player MPC. Another line of work has results about the power of correlated randomness; meaning in a preprocessing phase the participants in a MPC protocol receive samples from some joint distribution to aid them implement...

  10. A Survey on Underwater Acoustic Sensor Network Routing Protocols

    Directory of Open Access Journals (Sweden)

    Ning Li

    2016-03-01

    Full Text Available Underwater acoustic sensor networks (UASNs have become more and more important in ocean exploration applications, such as ocean monitoring, pollution detection, ocean resource management, underwater device maintenance, etc. In underwater acoustic sensor networks, since the routing protocol guarantees reliable and effective data transmission from the source node to the destination node, routing protocol design is an attractive topic for researchers. There are many routing algorithms have been proposed in recent years. To present the current state of development of UASN routing protocols, we review herein the UASN routing protocol designs reported in recent years. In this paper, all the routing protocols have been classified into different groups according to their characteristics and routing algorithms, such as the non-cross-layer design routing protocol, the traditional cross-layer design routing protocol, and the intelligent algorithm based routing protocol. This is also the first paper that introduces intelligent algorithm-based UASN routing protocols. In addition, in this paper, we investigate the development trends of UASN routing protocols, which can provide researchers with clear and direct insights for further research.

  11. The Bounded Retransmission Protocol must be on time!

    NARCIS (Netherlands)

    d' Argenio, P.R.; Katoen, Joost P.; Ruys, T.C.; Tretmans, G.J.

    1997-01-01

    This paper concerns the transfer of files via a lossy communication channel. It formally specifies this file transfer service in a property-oriented way and investigates -using two different techniques -whether a given bounded retransmission protocol conforms to this service. This protocol is based

  12. Epistemic Protocols for Distributed Gossiping

    Directory of Open Access Journals (Sweden)

    Krzysztof R. Apt

    2016-06-01

    Full Text Available Gossip protocols aim at arriving, by means of point-to-point or group communications, at a situation in which all the agents know each other's secrets. We consider distributed gossip protocols which are expressed by means of epistemic logic. We provide an operational semantics of such protocols and set up an appropriate framework to argue about their correctness. Then we analyze specific protocols for complete graphs and for directed rings.

  13. Composing Interfering Abstract Protocols

    Science.gov (United States)

    2016-04-01

    system by discussing how our core shared memory protocol framework is capable of expressing safe, typeful message-passing idioms . Next, we briefly...ends with discussions of expressiveness , related work, and conclusions. 1.1 Preliminaries: Language Overview Our language supports fork/join concurrency...the expressiveness of the full language , how we can model some high-level synchronization mechanisms, and clarify modularity gains when compared to

  14. Spermiologic examination protocol

    Directory of Open Access Journals (Sweden)

    Ye. Ye. Bragina

    2014-01-01

    Full Text Available The 2010 World Health Organization (WHO guidelines for semiological examinations describe standard, additional tests and tests of scientific value and analyze in detail different situations and possible errors. This paper gives an abstract of the WHO guidelines, a concise protocol for using the standard methods of a spermiolofic examination, and a number of commentaries that reflect the alternative view of a number of problems.

  15. In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study.

    Science.gov (United States)

    Krishna, Somashekar G; Modi, Rohan M; Kamboj, Amrit K; Swanson, Benjamin J; Hart, Phil A; Dillhoff, Mary E; Manilchuk, Andrei; Schmidt, Carl R; Conwell, Darwin L

    2017-05-14

    To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs). In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively. A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a "fern pattern" of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology. In vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.

  16. Offset protocols review report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-04-15

    A detailed offset system was established by the Western Climate Initiative (WCI) in an effort to support its cap-and-trade program. This report presented the results of evaluation of protocols that were identified by the partners of the WCI. The purpose of the evaluation was to help the WCI identify opportunities to incorporate existing protocols into the new offset system. The WCI's offset criteria were outlined in its offset system essential elements draft recommendations paper in which a WCI offset was defined as a quantified, independently verified reduction or removal of a greenhouse gas. Several findings were presented according to the commonalities and differences found in the protocols by project type, including soil sequestration; manure management; rangeland management; afforestation and reforestation; forest management; forest preservation and conservation; forest products; urban forestry; landfill gas; and waste and wastewater treatment. In addition, this report discussed the general evaluation approach used, work process flowchart, and stakeholder process of each offset system. refs., tabs., figs., appendices.

  17. Dysphonia risk screening protocol

    Directory of Open Access Journals (Sweden)

    Katia Nemr

    2016-03-01

    Full Text Available OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children, 29.25 (adult women, 22.75 (adult men, and 27.10 (seniors. CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics.

  18. Automatic Validation of Protocol Narration

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, Pierpablo

    2003-01-01

    We perform a systematic expansion of protocol narrations into terms of a process algebra in order to make precise some of the detailed checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we demons...

  19. Improving mood with psychoanalytic and cognitive therapies (IMPACT: a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Suckling John

    2011-07-01

    Full Text Available Abstract Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine

  20. Data-driven CT protocol review and management—experience from a large academic hospital.

    Science.gov (United States)

    Zhang, Da; Savage, Cristy A; Li, Xinhua; Liu, Bob

    2015-03-01

    Protocol review plays a critical role in CT quality assurance, but large numbers of protocols and inconsistent protocol names on scanners and in exam records make thorough protocol review formidable. In this investigation, we report on a data-driven cataloging process that can be used to assist in the reviewing and management of CT protocols. We collected lists of scanner protocols, as well as 18 months of recent exam records, for 10 clinical scanners. We developed computer algorithms to automatically deconstruct the protocol names on the scanner and in the exam records into core names and descriptive components. Based on the core names, we were able to group the scanner protocols into a much smaller set of "core protocols," and to easily link exam records with the scanner protocols. We calculated the percentage of usage for each core protocol, from which the most heavily used protocols were identified. From the percentage-of-usage data, we found that, on average, 18, 33, and 49 core protocols per scanner covered 80%, 90%, and 95%, respectively, of all exams. These numbers are one order of magnitude smaller than the typical numbers of protocols that are loaded on a scanner (200-300, as reported in the literature). Duplicated, outdated, and rarely used protocols on the scanners were easily pinpointed in the cataloging process. The data-driven cataloging process can facilitate the task of protocol review. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  1. A customised cold-water immersion protocol favours one-size-fits-all protocols in improving acute performance recovery

    NARCIS (Netherlands)

    Zandvoort, Coen S.; de Zwart, Jelmer R.; van Keeken, Brenda L.; Viroux, Patrick J.F.; Tiemessen, Ivo J.H.

    2017-01-01

    The purpose of the present study was to investigate whether a customised cold-water immersion (CWIc) protocol was more effective in enhancing acute performance recovery than a one-size-fits-all CWI (CWIs) or active recovery (AR) protocol. On three separate testing days, 10 healthy, physically

  2. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831).

    Science.gov (United States)

    Kean, James D; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

    2015-12-02

    Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

  3. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08 on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831

    Directory of Open Access Journals (Sweden)

    James D. Kean

    2015-12-01

    Full Text Available Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS. Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12612000827831.

  4. A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN study protocol [ISRCTN54195799

    Directory of Open Access Journals (Sweden)

    Whyte Ken

    2011-03-01

    Full Text Available Abstract Background Vitamin B12 deficiency is common in older people and the prevalence increases with age. Vitamin B12 deficiency may present as macrocytic anaemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. The diagnosis and indications for treatment are clear for individuals with low plasma levels of vitamin B12 in the setting of megaloblastic anaemia and neuropathy, but the relevance of treatment of vitamin B12 deficiency in the absence of such clinical signs is uncertain. Methods The aim of the present study is to assess whether dietary supplementation with crystalline vitamin B12 will improve electrophysiological indices of neurological function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of anaemia. To test this hypothesis we designed a randomized double-blind placebo-controlled trial involving 200 older people aged 75 years or greater who were randomly allocated to receive either a daily oral tablet containing 1 mg vitamin B12 or a matching placebo tablet. The primary outcome assessed at 12 months is change in electrophysiological indices of peripheral and central neurosensory responses required for mobility and sensory function. We here report the detailed study protocol. Conclusions In view of the high prevalence of vitamin B12 deficiency in later life, the present trial could have considerable significance for public health.

  5. Evaluation of counterfactuality in counterfactual communication protocols

    Science.gov (United States)

    Arvidsson-Shukur, D. R. M.; Barnes, C. H. W.; Gottfries, A. N. O.

    2017-12-01

    We provide an in-depth investigation of parameter estimation in nested Mach-Zehnder interferometers (NMZIs) using two information measures: the Fisher information and the Shannon mutual information. Protocols for counterfactual communication have, so far, been based on two different definitions of counterfactuality. In particular, some schemes have been based on NMZI devices, and have recently been subject to criticism. We provide a methodology for evaluating the counterfactuality of these protocols, based on an information-theoretical framework. More specifically, we make the assumption that any realistic quantum channel in MZI structures will have some weak uncontrolled interaction. We then use the Fisher information of this interaction to measure counterfactual violations. The measure is used to evaluate the suggested counterfactual communication protocol of H. Salih et al. [Phys. Rev. Lett. 110, 170502 (2013), 10.1103/PhysRevLett.110.170502]. The protocol of D. R. M. Arvidsson-Shukur and C. H. W. Barnes [Phys. Rev. A 94, 062303 (2016), 10.1103/PhysRevA.94.062303], based on a different definition, is evaluated with a probability measure. Our results show that the definition of Arvidsson-Shukur and Barnes is satisfied by their scheme, while that of Salih et al. is only satisfied by perfect quantum channels. For realistic devices the latter protocol does not achieve its objective.

  6. WDM network and multicasting protocol strategies.

    Science.gov (United States)

    Kirci, Pinar; Zaim, Abdul Halim

    2014-01-01

    Optical technology gains extensive attention and ever increasing improvement because of the huge amount of network traffic caused by the growing number of internet users and their rising demands. However, with wavelength division multiplexing (WDM), it is easier to take the advantage of optical networks and optical burst switching (OBS) and to construct WDM networks with low delay rates and better data transparency these technologies are the best choices. Furthermore, multicasting in WDM is an urgent solution for bandwidth-intensive applications. In the paper, a new multicasting protocol with OBS is proposed. The protocol depends on a leaf initiated structure. The network is composed of source, ingress switches, intermediate switches, edge switches, and client nodes. The performance of the protocol is examined with Just Enough Time (JET) and Just In Time (JIT) reservation protocols. Also, the paper involves most of the recent advances about WDM multicasting in optical networks. WDM multicasting in optical networks is given as three common subtitles: Broadcast and-select networks, wavelength-routed networks, and OBS networks. Also, in the paper, multicast routing protocols are briefly summarized and optical burst switched WDM networks are investigated with the proposed multicast schemes.

  7. WDM Network and Multicasting Protocol Strategies

    Directory of Open Access Journals (Sweden)

    Pinar Kirci

    2014-01-01

    Full Text Available Optical technology gains extensive attention and ever increasing improvement because of the huge amount of network traffic caused by the growing number of internet users and their rising demands. However, with wavelength division multiplexing (WDM, it is easier to take the advantage of optical networks and optical burst switching (OBS and to construct WDM networks with low delay rates and better data transparency these technologies are the best choices. Furthermore, multicasting in WDM is an urgent solution for bandwidth-intensive applications. In the paper, a new multicasting protocol with OBS is proposed. The protocol depends on a leaf initiated structure. The network is composed of source, ingress switches, intermediate switches, edge switches, and client nodes. The performance of the protocol is examined with Just Enough Time (JET and Just In Time (JIT reservation protocols. Also, the paper involves most of the recent advances about WDM multicasting in optical networks. WDM multicasting in optical networks is given as three common subtitles: Broadcast and-select networks, wavelength-routed networks, and OBS networks. Also, in the paper, multicast routing protocols are briefly summarized and optical burst switched WDM networks are investigated with the proposed multicast schemes.

  8. In aqua vivo EPID dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Wendling, Markus; McDermott, Leah N.; Mans, Anton; Olaciregui-Ruiz, Igor; Pecharroman-Gallego, Raul; Sonke, Jan-Jakob; Stroom, Joep; Herk, Marcel J.; Mijnheer, Ben van [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2012-01-15

    Purpose: At the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the original back-projection dose-reconstruction algorithm uses water-based scatter-correction kernels and therefore does not account for tissue inhomogeneities accurately. The aim of this study was to test a new method, in aqua vivo EPID dosimetry, for fast dose verification of lung cancer irradiations during actual patient treatment. Methods: The key feature of our method is the dose reconstruction in the patient from EPID images, obtained during the actual treatment, whereby the images have been converted to a situation as if the patient consisted entirely of water; hence, the method is termed in aqua vivo. This is done by multiplying the measured in vivo EPID image with the ratio of two digitally reconstructed transmission images for the unit-density and inhomogeneous tissue situation. For dose verification, a comparison is made with the calculated dose distribution with the inhomogeneity correction switched off. IMRT treatment verification is performed for each beam in 2D using a 2D {gamma} evaluation, while for the verification of volumetric-modulated arc therapy (VMAT) treatments in 3D a 3D {gamma} evaluation is applied using the same parameters (3%, 3 mm). The method was tested using two inhomogeneous phantoms simulating a tumor in lung and measuring its sensitivity for patient positioning errors. Subsequently five IMRT and five VMAT clinical lung cancer treatments were investigated, using both the conventional back-projection algorithm and the in aqua vivo method. The verification results of the in aqua vivo method were statistically analyzed for 751 lung cancer patients treated with IMRT and 50 lung cancer patients treated with VMAT. Results: The improvements by

  9. Application of pharmacogenomics to investigate adverse drug reactions to the disease-modifying treatments for multiple sclerosis: a case-control study protocol for dimethyl fumarate-induced lymphopenia.

    Science.gov (United States)

    Kowalec, Kaarina; Kingwell, Elaine; Carruthers, Robert; Marrie, Ruth Ann; Bernatsky, Sasha; Traboulsee, Anthony; Ross, Colin J D; Carleton, Bruce; Tremlett, Helen

    2017-06-02

    Adverse drug reactions (ADRs) are a global public health issue. The potential for pharmacogenomic biomarkers has been demonstrated in several therapeutical areas, including HIV infection and oncology. Dimethyl fumarate (DMF) is a licensed disease-modifying therapy for the treatment of multiple sclerosis (MS). The use of DMF in MS has been associated with a severe reduction in lymphocyte counts and reports of progressive multifocal leukoencephalopathy. Here, we outline the protocol for a case-control study designed to discover genomic variants associated with DMF-induced lymphopenia. The ultimate goal is to replicate these findings and create an efficient and adaptable approach towards the identification of genomic markers that could assist in mitigating adverse drug reactions in MS. The population sample will comprise DMF-exposed patients with MS, with cases representing those who developed lymphopenia and controls who did not. DNA genotyping will take place using a high-throughput genome-wide array. Fine mapping and imputation will be performed to focus in on the potentially causal variants associated with lymphopenia. Multivariable logistic regression will be used to compare genotype and allele frequencies between the cases and the controls, with consideration of potential confounders. The association threshold will be set at p<1.0×10 -5 for the discovery of genomic association analyses to select variants for replication. Ethics approval has been obtained from the respective research ethics board, which includes written informed consent. Findings will be disseminated widely, including at scientific conferences, via podcasts (targeted at both healthcare professionals as well as patients and the wider community), through patient engagement and other outreach community events, written lay summaries for all participants and formal publication in peer-reviewed scientific journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the

  10. Protocol for a mixed methods study investigating the impact of investment in housing, regeneration and neighbourhood renewal on the health and wellbeing of residents: the GoWell programme.

    Science.gov (United States)

    Egan, Matt; Kearns, Ade; Mason, Phil; Tannahill, Carol; Bond, Lyndal; Coyle, Jennie; Beck, Sheila; Crawford, Fiona; Hanlon, Phil; Lawson, Louise; McLean, Jennifer; Petticrew, Mark; Sautkina, Elena; Thomson, Hilary; Walsh, David

    2010-05-11

    There is little robust evidence to test the policy assumption that housing-led area regeneration strategies will contribute to health improvement and reduce social inequalities in health. The GoWell Programme has been designed to measure effects on health and wellbeing of multi-faceted regeneration interventions on residents of disadvantaged neighbourhoods in the city of Glasgow, Scotland. This mixed methods study focused (initially) on 14 disadvantaged neighbourhoods experiencing regeneration. These were grouped by intervention into 5 categories for comparison. GoWell includes a pre-intervention householder survey (n = 6008) and three follow-up repeat-cross sectional surveys held at two or three year intervals (the main focus of this protocol) conducted alongside a nested longitudinal study of residents from 6 of those areas. Self-reported responses from face-to-face questionnaires are analysed along with various routinely produced ecological data and documentary sources to build a picture of the changes taking place, their cost and impacts on residents and communities. Qualitative methods include interviews and focus groups of residents, housing managers and other stakeholders exploring issues such as the neighbourhood context, potential pathways from regeneration to health, community engagement and empowerment. Urban regeneration programmes are 'natural experiments.' They are complex interventions that may impact upon social determinants of population health and wellbeing. Measuring the effects of such interventions is notoriously challenging. GoWell compares the health and wellbeing effects of different approaches to regeneration, generates theory on pathways from regeneration to health and explores the attitudes and responses of residents and other stakeholders to neighbourhood change.

  11. Investigation of PDE5/PDE6 and PDE5/PDE11 selective potent tadalafil-like PDE5 inhibitors using combination of molecular modeling approaches, molecular fingerprint-based virtual screening protocols and structure-based pharmacophore development.

    Science.gov (United States)

    Kayık, Gülru; Tüzün, Nurcan Ş; Durdagi, Serdar

    2017-12-01

    The essential biological function of phosphodiesterase (PDE) type enzymes is to regulate the cytoplasmic levels of intracellular second messengers, 3',5'-cyclic guanosine monophosphate (cGMP) and/or 3',5'-cyclic adenosine monophosphate (cAMP). PDE targets have 11 isoenzymes. Of these enzymes, PDE5 has attracted a special attention over the years after its recognition as being the target enzyme in treating erectile dysfunction. Due to the amino acid sequence and the secondary structural similarity of PDE6 and PDE11 with the catalytic domain of PDE5, first-generation PDE5 inhibitors (i.e. sildenafil and vardenafil) are also competitive inhibitors of PDE6 and PDE11. Since the major challenge of designing novel PDE5 inhibitors is to decrease their cross-reactivity with PDE6 and PDE11, in this study, we attempt to identify potent tadalafil-like PDE5 inhibitors that have PDE5/PDE6 and PDE5/PDE11 selectivity. For this aim, the similarity-based virtual screening protocol is applied for the "clean drug-like subset of ZINC database" that contains more than 20 million small compounds. Moreover, molecular dynamics (MD) simulations of selected hits complexed with PDE5 and off-targets were performed in order to get insights for structural and dynamical behaviors of the selected molecules as selective PDE5 inhibitors. Since tadalafil blocks hERG1 K channels in concentration dependent manner, the cardiotoxicity prediction of the hit molecules was also tested. Results of this study can be useful for designing of novel, safe and selective PDE5 inhibitors.

  12. Protocol for a mixed methods study investigating the impact of investment in housing, regeneration and neighbourhood renewal on the health and wellbeing of residents: the GoWell programme

    Directory of Open Access Journals (Sweden)

    Petticrew Mark

    2010-05-01

    Full Text Available Abstract Background There is little robust evidence to test the policy assumption that housing-led area regeneration strategies will contribute to health improvement and reduce social inequalities in health. The GoWell Programme has been designed to measure effects on health and wellbeing of multi-faceted regeneration interventions on residents of disadvantaged neighbourhoods in the city of Glasgow, Scotland. Methods/Design This mixed methods study focused (initially on 14 disadvantaged neighbourhoods experiencing regeneration. These were grouped by intervention into 5 categories for comparison. GoWell includes a pre-intervention householder survey (n = 6008 and three follow-up repeat-cross sectional surveys held at two or three year intervals (the main focus of this protocol conducted alongside a nested longitudinal study of residents from 6 of those areas. Self-reported responses from face-to-face questionnaires are analysed along with various routinely produced ecological data and documentary sources to build a picture of the changes taking place, their cost and impacts on residents and communities. Qualitative methods include interviews and focus groups of residents, housing managers and other stakeholders exploring issues such as the neighbourhood context, potential pathways from regeneration to health, community engagement and empowerment. Discussion Urban regeneration programmes are 'natural experiments.' They are complex interventions that may impact upon social determinants of population health and wellbeing. Measuring the effects of such interventions is notoriously challenging. GoWell compares the health and wellbeing effects of different approaches to regeneration, generates theory on pathways from regeneration to health and explores the attitudes and responses of residents and other stakeholders to neighbourhood change.

  13. Internet Protocol Transition Workbook

    Science.gov (United States)

    1982-03-01

    VGC] 020.rrr.rrr.rrr DC-PR D.C. Packet Radio Network [VGCJ 021.rrr.rrr.rrr EDN OCEC EON [EC5] 022.rrr.rrr.rrr DIALNET DIALNE1 (26, 16.MRCJ 023...41953. 7 October 1977. Also in [17]. [16] Crispin. M. and I. Zabala. " DIALNET Protocols". Stanford University Artificial Intelligence Laboratory, July...34. IEN 158. October 1980. (26] McCarthy, J. and L. Earnest, " DIALNET ", Stanford University Artificial Intelligence Laboratory, Undated. (27] McKenzie

  14. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Human Resources Division

    2000-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.

  15. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Division du Personnel

    1999-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

  16. Optimization (Central Composite Design and Validation of HPLC Method for Investigation of Emtricitabine Loaded Poly(lactic-co-glycolic acid Nanoparticles: In Vitro Drug Release and In Vivo Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Gurinder Singh

    2014-01-01

    Full Text Available The objective of the current study is to develop nanoparticles (NPs drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid (PLGA and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD. NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8, methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040–2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4. In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs.

  17. Feasibility study of a randomised controlled trial to investigate the effectiveness of using a humanoid robot to improve the social skills of children with autism spectrum disorder (Kaspar RCT): a study protocol.

    Science.gov (United States)

    Mengoni, Silvana E; Irvine, Karen; Thakur, Deepshikha; Barton, Garry; Dautenhahn, Kerstin; Guldberg, Karen; Robins, Ben; Wellsted, David; Sharma, Shivani

    2017-06-22

    Interventions using robot-assisted therapy may be beneficial for the social skills development of children with autism spectrum disorder (ASD); however, randomised controlled trials (RCTs) are lacking. The present research aims to assess the feasibility of conducting an RCT evaluating the effectiveness of a social skills intervention using Kinesics and Synchronisation in Personal Assistant Robotics (Kaspar) with children with ASD. Forty children will be recruited. Inclusion criteria are the following: aged 5-10 years, confirmed ASD diagnosis, IQ over 70, English-language comprehension, a carer who can complete questionnaires in English and no current participation in a private social communication intervention. Children will be randomised to receive an intervention with a therapist and Kaspar, or with the therapist only. They will receive two familiarisation sessions and six treatment sessions for 8 weeks. They will be assessed at baseline, and at 10 and 22 weeks after baseline. The primary outcome of this study is to evaluate whether the predetermined feasibility criteria for a full-scale trial are met. The potential primary outcome measures for a full-scale trial are the Social Communication Questionnaire and the Social Skills Improvement System. We will conduct a preliminary economic analysis. After the study has ended, a sample of 20 participants and their families will be invited to participate in semistructured interviews to explore the feasibility and acceptability of the study's methods and intervention. Parents/carers will provide informed consent, and children will give assent, where appropriate. Care will be taken to avoid pressure or coercion to participate. Aftercare is available from the recruiting NHS Trust, and a phased withdrawal protocol will be followed if children become excessively attached to the robot. The results of the study will be disseminated to academic audiences and non-academic stakeholders, for example, families of children

  18. Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.

    Science.gov (United States)

    Marjanovic, Nicolas; Frasca, Denis; Asehnoune, Karim; Paugam, Catherine; Lasocki, Sigismond; Ichai, Carole; Lefrant, Jean-Yves; Leone, Marc; Dahyot-Fizelier, Claire; Pottecher, Julien; Falcon, Dominique; Veber, Benoit; Constantin, Jean-Michel; Seguin, Sabrina; Guénézan, Jérémy; Mimoz, Olivier

    2017-08-07

    Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. Clinical Trials NCT02534974. © Article author(s) (or

  19. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  20. A protected password change protocol

    OpenAIRE

    Wang, Ren-Chiun; Yang, Chou-Chen; Mo, Kun-Ru

    2005-01-01

    Some protected password change protocols were proposed. However, the previous protocols were easily vulnerable to several attacks such as denial of service, password guessing, stolen-verifier and impersonation atacks etc. Recently, Chang et al. proposed a simple authenticated key agreement and protected password change protocol for enhancing the security and efficiency. In this paper, authors shall show that password guessing, denial of service and known-key attacks can work in their password...

  1. An Improved Resource Reservation Protocol

    OpenAIRE

    Desire Oulai; Steven Chamberland; Samuel Pierre

    2007-01-01

    The classical resource reservation protocol (RSVP) is a flow-based signaling protocol used for reserving resources in the network for a given session. RSVP maintains state information for each reservation at every router along the path. Even though this protocol is very popular, he has some weaknesses. Indeed, RSVP does not include a bidirectional reservation process and it requires refresh messages to maintain the soft states in the routers for each session. In this paper, we propose a...

  2. Static Validation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, P.

    2005-01-01

    We methodically expand protocol narrations into terms of a process algebra in order to specify some of the checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we demonstrate that these techniques...... suffice to identify several authentication flaws in symmetric and asymmetric key protocols such as Needham-Schroeder symmetric key, Otway-Rees, Yahalom, Andrew secure RPC, Needham-Schroeder asymmetric key, and Beller-Chang-Yacobi MSR...

  3. Ischemic small intestine-in vivo versus ex vivo bioimpedance measurements.

    Science.gov (United States)

    Strand-Amundsen, Runar J; Reims, Henrik M; Tronstad, Christian; Kalvøy, Håvard; Martinsen, Ørjan G; Høgetveit, Jan O; Ruud, Tom E; Tønnessen, Tor I

    2017-05-01

    Bioimpedance has been used to investigate changes in electrical parameters during ischemia in various tissues. The small intestine is a multi-layered structure, with several distinct tissue types, and ischemia related changes occur at different times in the different intestinal layers. When investigating how the electrical properties in the small intestine is affected by ischemia, some researchers have used ex vivo models while others have used in vivo models. In this study, we compare ischemic time development of electrical parameters in ischemic in vivo versus ex vivo small intestine. Measurements were performed using a two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. Electrodes were placed on the surface of ischemic pig jejunum, applying a voltage and measuring the resulting electrical admittance. In each pig, 4 segments of the jejunum were made ischemic by clamping the mesenteric arteries and veins, resulting in a 30 cm central zone of warm ischemia and edema. The in vivo part of the experiment lasted 10 h, after which 3 pieces of perfused small intestine were resected, stored in Ringer-acetat at 38 °C, and measured during a 10 h ex vivo experiment. Main results and significance: We found significant differences (p  vivo and ex vivo measurements as a function of ischemic time development. We also observed some similarities in the trends. In vivo, we measured an overall decrease in impedance during the duration of the experiment, probably as a result from the formation of edema. Ex vivo, the low frequency impedance increased initially for approximately 3 h before starting to decrease.

  4. Protocols for Scholarly Communication

    CERN Document Server

    Pepe, Alberto; Pepe, Alberto; Yeomans, Joanne

    2007-01-01

    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should naturally guide authors towards OA publication and CERN wants to help reach a full...

  5. A "release" protocol for isothermal titration calorimetry.

    Science.gov (United States)

    Heerklotz, H H; Binder, H; Epand, R M

    1999-05-01

    Isothermal titration calorimetry (ITC) has become a standard method for investigating the binding of ligands to receptor molecules or the partitioning of solutes between water and lipid vesicles. Accordingly, solutes are mixed with membranes (or ligands with receptors), and the subsequent heats of incorporation (or binding) are measured. In this paper we derive a general formula for modeling ITC titration heats in both binding and partitioning systems that allows for the modeling of the classic incorporation or binding protocols, as well as of new protocols assessing the release of solute from previously solute-loaded vesicles (or the dissociation of ligand/receptor complexes) upon dilution. One major advantage of a simultaneous application of the incorporation/binding and release protocols is that it allows for the determination of whether a ligand is able to access the vesicle interior within the time scale of the ITC experiment. This information cannot be obtained from a classical partitioning experiment, but it must be known to determine the partition coefficient (or binding constant and stochiometry) and the transfer enthalpy. The approach is presented using the partitioning of the nonionic detergent C12EO7 to palmitoyloleoylphosphatidylcholine vesicles. The release protocol could also be advantageous in the case of receptors that are more stable in the ligand-saturated rather than the ligand-depleted state.

  6. The UMTS-AKA Protocols for Intelligent Transportation Systems

    Directory of Open Access Journals (Sweden)

    Hwang Min-Shiang

    2009-01-01

    Full Text Available The integration of communication protocols into transport systems is a much adored research area today. Much of seminal work has been reported on the topic of intelligent transportation systems (ITS in the recent years. Many advanced techniques have been garnered to improve online communication and to promote the security, comfort, and efficiency of ITS. Of primary importance to the effective application of ITS is the communication protocol used. A fascinating development is that the yesterday's Global System for Mobile Communication protocol is being replaced by the Universal Mobile Telecommunication System protocol, which is the third-generation mobile technology. This article attempts to identify a suitable communication system for ITS applications. It is impracticable to substantially modify the original UMTS-IMS-AKA protocol which is in practice because it can disturb the operation of the current system, and thus we explore other possibilities through this research. We investigate a novel protocol to make the original UMTS-IMS-AKA protocol compliant with ITS as well as adaptable into the current UMTS protocol.

  7. Protocols for Robotic Telescope Networks

    Directory of Open Access Journals (Sweden)

    Alain Klotz

    2010-01-01

    This paper is addressed to astronomers who are not specialists in computer science. We give explanations of some basic and advanced protocols to receive events and how to implement them in a robotic observatory software. We describe messages such as GCN notices, VOEvents or RTML, and protocols such as CGI, HTTP, SOAP, RSS, and XMPP.

  8. Publishing protocols for partnered research.

    Science.gov (United States)

    Hysong, Sylvia J; Woodard, LeChauncy; Garvin, Jennifer H; Murawsky, Jeffrey; Petersen, Laura A

    2014-12-01

    Published scientific protocols are advocated as a means of controlling bias in research reporting. Indeed, many journals require a study protocol with manuscript submission. However, publishing protocols of partnered research (PPR) can be challenging in light of the research model's dynamic nature, especially as no current reporting standards exist. Nevertheless, as these protocols become more prevalent, a priori documentation of methods in partnered research studies becomes increasingly important. Using as illustration a suite of studies aimed at improving coordination and communication in the primary care setting, we sought to identify challenges in publishing PPR relative to traditional designs, present alternative solutions to PPR publication, and propose an initial checklist of content to be included in protocols of partnered research. Challenges to publishing PPR include reporting details of research components intended to be co-created with operational partners, changes to sampling and entry strategy, and alignment of scientific and operational goals. Proposed solutions include emulating reporting standards of qualitative research, participatory action research, and adaptive trial designs, as well as embracing technological tools that facilitate publishing adaptive protocols, with version histories that are able to be updated as major protocol changes occur. Finally, we present a proposed checklist of reporting elements for partnered research protocols.

  9. Gene probes: principles and protocols

    National Research Council Canada - National Science Library

    Rapley, Ralph; Aquino de Muro, Marilena

    2002-01-01

    ... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

  10. Risk Balance in Exchange Protocols

    NARCIS (Netherlands)

    M.T. Dashti (Mohammad); Y. Wang (Yanjing); I. Cervesato

    2007-01-01

    htmlabstractWe study the behaviour of rational agents in exchange protocols which rely on trustees. We allow malicious parties to compromise the trustee by paying a cost and, thereby, present a game analysis that advocates exchange protocols which induce balanced risks on the participants. We also

  11. Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Zaher, Walid; Larsen, Kenneth H

    2015-01-01

    INTRODUCTION: There is a clinical need for developing systemic transplantation protocols for use of human skeletal stem cells (also known bone marrow stromal stem cells) (hBMSC) in tissue regeneration. In systemic transplantation studies, only a limited number of hBMSC home to injured tissues...... vivo transwell migration and following intravenous injection, better in vivo homing ability to bone fracture when compared to LBF clones. Comparative microarray analysis of HBF versus LBF clones identified enrichment of gene categories of chemo-attraction, adhesion and migration associated genes. Among...

  12. Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Christensen, Britt; Lundby, Carsten; Jessen, Niels

    2012-01-01

    as activation of Epo signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting. Changes in muscle protein profiles after prolonged erythropoietin treatment were evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the erythropoietin receptor in skeletal muscle......Background: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. Methodology/Principal Findings: The protocols...... involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well...

  13. Growing old at home – A randomized controlled trial to investigate the effectiveness and cost-effectiveness of preventive home visits to reduce nursing home admissions: study protocol [NCT00644826

    Directory of Open Access Journals (Sweden)

    Riedel-Heller Steffi G

    2008-05-01

    Full Text Available Abstract Background Regarding demographic changes in Germany it can be assumed that the number of elderly and the resulting need for long term care is increasing in the near future. It is not only an individual's interest but also of public concern to avoid a nursing home admission. Current evidence indicates that preventive home visits can be an effective way to reduce the admission rate in this way making it possible for elderly people to stay longer at home than without home visits. As the effectiveness and cost-effectiveness of preventive home visits strongly depends on existing services in the social and health system existing international results cannot be merely transferred to Germany. Therefore it is necessary to investigate the effectiveness and cost-effectiveness of such an intervention in Germany by a randomized controlled trial. Methods The trial is designed as a prospective multi-center randomized controlled trial in the cities of Halle and Leipzig. The trial includes an intervention and a control group. The control group receives usual care. The intervention group receives three additional home visits by non-physician health professionals (1 geriatric assessment, (2 consultation, (3 booster session. The nursing home admission rate after 18 months will be defined as the primary outcome. An absolute risk reduction from a 20% in the control-group to a 7% admission rate in the intervention group including an assumed drop out rate of 30% resulted in a required sample size of N = 320 (n = 160 vs. n = 160. Parallel to the clinical outcome measurement the intervention will be evaluated economically. The economic evaluation will be performed from a society perspective. Discussion To the authors' knowledge for the first time a trial will investigate the effectiveness and cost-effectiveness of preventive home visits for people aged 80 and over in Germany using the design of a randomized controlled trial. Thus, the trial will contribute to

  14. Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model

    Directory of Open Access Journals (Sweden)

    Otto Andreas

    2010-01-01

    Full Text Available Abstract Background Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO in a large animal model. Methods A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg. The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8 or saline (0.9 mg/ml, n = 8, twenty minutes after balloon inflation. Area at risk (AAR was evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI. Results No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS, but apyrase prolonged the post-ischemic reactive hyperemia. Conclusion Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.

  15. Measurement of bacterial gene expression in vivo by laser capture microdissection and quantitative real-time RT-PCR

    DEFF Research Database (Denmark)

    Schou, Kirstine Klitgaard; Jensen, Tim Kåre; Angen, Øystein

    2007-01-01

    Due to the relative small number of bacterial pathogens present in an infected host, exploration of pathogen gene expression in vivo is challenging. This study reports the development of a protocol for quantifying bacterial gene expression in vivo in Actinobacillus pleuropneumoniae using laser ca...... capture microdissection and real-time quantitative RT-PCR....

  16. ex vivo DNA assembly

    Directory of Open Access Journals (Sweden)

    Adam B Fisher

    2013-10-01

    Full Text Available Even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. Advances in cloning techniques have resulted in powerful in vitro and in vivo assembly of DNA. However, monetary and time costs have limited these approaches. Here, we report an ex vivo DNA assembly method that uses cellular lysates derived from a commonly used laboratory strain of Escherichia coli for joining double-stranded DNA with short end homologies embedded within inexpensive primers. This method concurrently shortens the time and decreases costs associated with current DNA assembly methods.

  17. [Advances of in vivo confocal scanning laser microscopy].

    Science.gov (United States)

    Tian, Ke-bin; Zhou, Guo-yu

    2006-02-01

    In vivo confocal scanning laser microscopy is being widely established as a time-saving, non-invasive, investigative methods in the study of body surfaces. Skin can be observed in its native state in vivo without the fixing, sectioning and staining that is necessary for routine histology. It is a new technology that can provide detailed images of tissue architecture and cellular morphology of living tissue. This paper reviews the fundamentals of in vivo confocal imaging and its clinical applications.

  18. Site-specific chromatin immunoprecipitation: a selective method to individually analyze neighboring transcription factor binding sites in vivo

    Directory of Open Access Journals (Sweden)

    Schuch Ronaldo

    2012-02-01

    Full Text Available Abstract Background Transcription factors (TFs and their binding sites (TFBSs play a central role in the regulation of gene expression. It is therefore vital to know how the allocation pattern of TFBSs affects the functioning of any particular gene in vivo. A widely used method to analyze TFBSs in vivo is the chromatin immunoprecipitation (ChIP. However, this method in its present state does not enable the individual investigation of densely arranged TFBSs due to the underlying unspecific DNA fragmentation technique. This study describes a site-specific ChIP which aggregates the benefits of both EMSA and in vivo footprinting in only one assay, thereby allowing the individual detection and analysis of single binding motifs. Findings The standard ChIP protocol was modified by replacing the conventional DNA fragmentation, i. e. via sonication or undirected enzymatic digestion (by MNase, through a sequence specific enzymatic digestion step. This alteration enables the specific immunoprecipitation and individual examination of occupied sites, even in a complex system of adjacent binding motifs in vivo. Immunoprecipitated chromatin was analyzed by PCR using two primer sets - one for the specific detection of precipitated TFBSs and one for the validation of completeness of the enzyme digestion step. The method was established exemplary for Sp1 TFBSs within the egfr promoter region. Using this site-specific ChIP, we were able to confirm four previously described Sp1 binding sites within egfr promoter region to be occupied by Sp1 in vivo. Despite the dense arrangement of the Sp1 TFBSs the improved ChIP method was able to individually examine the allocation of all adjacent Sp1 TFBS at once. The broad applicability of this site-specific ChIP could be demonstrated by analyzing these SP1 motifs in both osteosarcoma cells and kidney carcinoma tissue. Conclusions The ChIP technology is a powerful tool for investigating transcription factors in vivo, especially

  19. Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models.

    Directory of Open Access Journals (Sweden)

    Lucie Carolle Kenmogne

    Full Text Available In the fight against androgen-sensitive prostate cancer, the enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3 is an attractive therapeutic target considering its key role in the formation of androgenic steroids. In this study, we attempted to assess the in vivo efficacy of the compound RM-532-105, an androsterone derivative developed as an inhibitor of 17β-HSD3, in the prostate cancer model of androgen-sensitive LAPC-4 cells xenografted in nude mice. RM-532-105 did not inhibit the tumor growth induced by 4-androstene-3,17-dione (4-dione; rather, the levels of the androgens testosterone (T and dihydrotestosterone (DHT increased within the tumors. In plasma, however, DHT levels increased but T levels did not. In troubleshooting experiments, the non-androgenic potential of RM-532-105 was confirmed by two different assays (LAPC-4 proliferation and androgen receptor transcriptional activity assays. The enzyme 5α-reductase was also revealed to be the predominant enzyme metabolizing 4-dione in LAPC-4 cells, yielding 5α-androstane-3,17-dione and not T. Other 17β-HSDs than 17β-HSD3 seem responsible in the androgen synthesis. From experiments with LAPC-4 cells, we fortuitously came across the interesting finding that 17β-HSD3 inhibitor RM-532-105 is concentrated inside tumors.

  20. The effect of standard and transepithelial ultraviolet collagen cross-linking on human corneal nerves: an ex vivo study.

    Science.gov (United States)

    Al-Aqaba, Mouhamed; Calienno, Roberta; Fares, Usama; Otri, Ahmad Muneer; Mastropasqua, Leonardo; Nubile, Mario; Dua, Harminder S

    2012-02-01

    To evaluate the early effect of standard and transepithelial collagen cross-linking on human corneal nerves in donor eyes by ex vivo confocal microscopy and acetylcholinesterase staining. Experimental laboratory investigation. Eight human eye bank corneal buttons (mean age, 73.6 years) were included. Ultraviolet A collagen cross-linking was performed postmortem on 3 corneas with the standard protocol involving epithelial debridement and 4 corneas by the transepithelial approach. One cornea served as a control. Corneal nerves were evaluated using confocal microscopy and acetylcholinesterase histology. Confocal microscopy demonstrated the absence of subbasal nerves in corneas treated by the standard technique. These nerves were preserved in corneas treated by the transepithelial approach. Stromal nerves were visible in both groups. Histology of corneas treated by the standard technique revealed localized swellings of the stromal nerves with disruption of axonal membrane and loss of axonal continuity within the treatment zone. These changes were absent in corneas treated by the transepithelial approach. This study highlights the immediate effects of collagen cross-linking on the corneal nerves in an ex vivo model. The absence of subbasal nerves in the early phase of treatment appears to be attributable mainly to mechanical removal of epithelium, rather than ultraviolet light-induced damage. Localized swelling of the stromal nerves was the main difference between the 2 treatment protocols. Further research on laboratory animals would be necessary to verify these changes over a specified time course without the super-addition of postmortem changes. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Morinda citrifolia Linn (Noni): in vivo and in vitro reproductive toxicology.

    Science.gov (United States)

    Müller, Juliane C; Botelho, Giuliana G K; Bufalo, Aedra C; Boareto, Ana C; Rattmann, Yanna D; Martins, Elisangela S; Cabrini, Daniela A; Otuki, Michel F; Dalsenter, Paulo R

    2009-01-21

    Morinda citrifolia Linn (syn. Noni) is a plant widely used as food and medicine worldwide but there are no toxicological tests about this plant focused on reproduction. To investigate possible endocrine activity and toxic effect on the reproductive system of Wistar rats by exposure of aqueous extract of the Morinda citrifolia. Two experimental protocols in vivo were developed, (a) uterotrophic assay and (b) in utero and lactational assay, and one test in vitro to investigate the effect on the contractility of pregnant uteri isolated from rats (doses of the extract: 7.5, 75 and 750 mg/kg). The uterotrophic assay indicates presence of in vivo antiestrogenic activity of extract at doses of 7.5 and 750 mg/kg. The in utero and lactation exposure showed that the treatment with extract at the dose of 7.5mg/kg induced a reduction of 50% in parturition index and an increase of 74% in postimplantation losses index. The in vitro test showed that uteri from rats treated with 7.5mg/kg of the extract presented a 50% reduction on contraction induced by arachidonic acid. The exposure of aqueous extract of Morinda citrifolia in Wistar rats induced reproductive toxicity in nonlinear dose-response.

  2. Scaphoid kinematics in vivo

    NARCIS (Netherlands)

    Moojen, Thybout M.; Snel, Jeroen G.; Ritt, Marco J. P. F.; Venema, Henk W.; Kauer, John M. G.; Bos, Kurt E.

    2002-01-01

    The purpose of this study was to quantify 3-dimensional (3-D) in vivo scaphoid kinematics during flexion-extension motion (FEM) and radial-ulnar deviation (RUD) of the hand. The right wrists of 11 healthy volunteers were imaged by spiral computed tomography during RUD and 5 of those wrists also

  3. An improved vitrification protocol for equine immature oocytes, resulting in a first live foal.

    Science.gov (United States)

    Ortiz-Escribano, N; Bogado Pascottini, O; Woelders, H; Vandenberghe, L; De Schauwer, C; Govaere, J; Van den Abbeel, E; Vullers, T; Ververs, C; Roels, K; Van De Velde, M; Van Soom, A; Smits, K

    2017-08-20

    The success rate for vitrification of immature equine oocytes is low. Although vitrified-warmed oocytes are able to mature, further embryonic development appears to be compromised. The aim of this study was to compare two vitrification protocols, and to examine the effect of the number of layers of cumulus cells surrounding the oocyte during vitrification of immature equine oocytes. Experimental in vitro and in vivo trials. Immature equine oocytes were vitrified after a short exposure to high concentrations of cryoprotective agents (CPAs), or a long exposure to lower concentrations of CPAs. In Experiment 1, the maturation of oocytes surrounded by multiple layers of cumulus cells (CC oocytes) and oocytes surrounded by only corona radiata (CR oocytes) was investigated. In Experiment 2, spindle configuration was determined for CR oocytes vitrified using the two vitrification protocols. In Experiment 3, further embryonic development was studied after fertilisation and culture. Embryo transfer was performed in a standard manner. Similar nuclear maturation rates were observed for CR oocytes vitrified using the long exposure and nonvitrified controls. Furthermore, a lower maturation rate was obtained for CC oocytes vitrified with the short exposure compared to control CR oocytes (P = 0.001). Both vitrification protocols resulted in significantly higher rates of aberrant spindle configuration than the control groups (Pfoal. The relatively low number of equine oocytes and embryo transfer procedures performed. For vitrification of immature equine oocytes, the use of 1) CR oocytes, 2) a high concentration of CPAs, and 3) a short exposure time may be key factors for maintaining developmental competence. © 2017 EVJ Ltd.

  4. New Protocol for Skin Landmark Registration in Image-Guided Neurosurgery: Technical Note.

    Science.gov (United States)

    Gerard, Ian J; Hall, Jeffery A; Mok, Kelvin; Collins, D Louis

    2015-09-01

    Newer versions of the commercial Medtronic StealthStation allow the use of only 8 landmark pairs for patient-to-image registration as opposed to 9 landmarks in older systems. The choice of which landmark pair to drop in these newer systems can have an effect on the quality of the patient-to-image registration. To investigate 4 landmark registration protocols based on 8 landmark pairs and compare the resulting registration accuracy with a 9-landmark protocol. Four different protocols were tested on both phantoms and patients. Two of the protocols involved using 4 ear landmarks and 4 facial landmarks and the other 2 involved using 3 ear landmarks and 5 facial landmarks. Both the fiducial registration error and target registration error were evaluated for each of the different protocols to determine any difference between them and the 9-landmark protocol. No difference in fiducial registration error was found between any of the 8-landmark protocols and the 9-landmark protocol. A significant decrease (P registration error was found when using a protocol based on 4 ear landmarks and 4 facial landmarks compared with the other protocols based on 3 ear landmarks. When using 8 landmarks to perform the patient-to-image registration, the protocol using 4 ear landmarks and 4 facial landmarks greatly outperformed the other 8-landmark protocols and 9-landmark protocol, resulting in the lowest target registration error.

  5. Evaluation of rapid protocols for DNA isolation from Cercospora beticola Sacc.

    Directory of Open Access Journals (Sweden)

    Budakov Dragana

    2012-01-01

    Full Text Available The most fungal DNA isolation protocols are designed to obtain high amounts of very pure DNA, requiring large fungal cultures and extraction procedures with many purification steps. Since the PCR does not require high purity DNA, the aim of this investigation was to evaluate three fast and simple fungal DNA isolation protocols for further use in Cercospora PCR based research. The purity and quantity of isolated DNAs were determined spectrophotometrically, electrophoretically and by PCR reaction with universal primers. The amounts of DNA evaluated on agarose gels, isolated by protocols A and C, did not correspond to the spectrophotometrical values, probably due to RNA impurities. In samples isolated by protocol B these impurities were not detected and the DNA concentrations were more similar. Neither protocol eliminated impurities such as carbohydrates and phenol. The average DNA yield of protocol A was 1.04 μg/μl, protocol B 0.88 μg/μl, and protocol C 0.55 μg/μl. The DNA quality most suitable for PCR analysis was obtained by protocol A, where amplification product with universal primers was detected in all DNA samples. The amplification product was detected in 87% of samples isolated by protocol C and in only 60% of samples isolated by protocol B. Although DNA obtained by protocol A had the highest yield and best quality, the isolation protocol C should be also recommended, for it does not require phenol, chlorophorm or liquid nitrogen.

  6. A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI study protocol (ANZCTR12611000487910

    Directory of Open Access Journals (Sweden)

    Stough Con K

    2012-03-01

    Full Text Available Abstract Background One of the major challenges associated with our ageing population is the increasing incidence of age-associated cognitive decline, which has significant implications for an individual's ability to lead a productive and fulfilling life. In pure economic terms the costs of ageing reflects decreased productivity and engagement with the workforce. The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle. In light of this, the role of diet, including supplementation with nutritional and even pharmacological interventions capable of ameliorating the neurocognitive changes that occur with age constitute vital areas of research. Methods In order to reduce cognitive ageing, the ARC longevity intervention (ARCLI was developed to examine the effects of two promising natural pharmacologically active supplements on cognitive performance. ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in which 465 participants will be randomized to receive an extract of Bacopa monnieri (CDRI08 300 mg/day, Pycnogenol (150 mg/day, or placebo daily for 12 months. Participants will be tested at baseline and then at 3, 6 and 12 months post-randomization on a wide battery of cognitive, neuropsychological and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness, biochemical (assays to measure inflammation, oxidative stress and safety as well as genetic assessments (telomere length and several Single Nucleotide Polymorphisms. The primary aim is to investigate the effects of these supplements on cognitive performance. The secondary aims are to explore the time-course of cognitive enhancement as well as potential cardiovascular and biochemical mechanisms underpinning cognitive enhancement over the 12 months of administration. ARCLI will represent one of the largest and most comprehensive

  7. Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment [ISRCTN08045231

    Directory of Open Access Journals (Sweden)

    Mutrie Nanette

    2006-02-01

    Full Text Available Abstract Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i reducing the dietary intake of fat to ~25% of the total calories, (ii eating at least 5 portions of fruit and vegetables a day, (iii increasing the intake of fibre and reducing refined carbohydrates, and (iv taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression, cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two

  8. Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment [ISRCTN08045231].

    Science.gov (United States)

    Saxton, John M; Daley, Amanda; Woodroofe, Nicola; Coleman, Robert; Powers, Hilary; Mutrie, Nanette; Siddall, Vanessa; Crank, Helen

    2006-02-09

    Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to approximately 25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long

  9. A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)

    Science.gov (United States)

    2012-01-01

    Background One of the major challenges associated with our ageing population is the increasing incidence of age-associated cognitive decline, which has significant implications for an individual's ability to lead a productive and fulfilling life. In pure economic terms the costs of ageing reflects decreased productivity and engagement with the workforce. The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle. In light of this, the role of diet, including supplementation with nutritional and even pharmacological interventions capable of ameliorating the neurocognitive changes that occur with age constitute vital areas of research. Methods In order to reduce cognitive ageing, the ARC longevity intervention (ARCLI) was developed to examine the effects of two promising natural pharmacologically active supplements on cognitive performance. ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in which 465 participants will be randomized to receive an extract of Bacopa monnieri (CDRI08 300 mg/day), Pycnogenol (150 mg/day), or placebo daily for 12 months. Participants will be tested at baseline and then at 3, 6 and 12 months post-randomization on a wide battery of cognitive, neuropsychological and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness), biochemical (assays to measure inflammation, oxidative stress and safety) as well as genetic assessments (telomere length and several Single Nucleotide Polymorphisms). The primary aim is to investigate the effects of these supplements on cognitive performance. The secondary aims are to explore the time-course of cognitive enhancement as well as potential cardiovascular and biochemical mechanisms underpinning cognitive enhancement over the 12 months of administration. ARCLI will represent one of the largest and most comprehensive experimental clinical

  10. Single blind randomized Phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lips Irene M

    2011-12-01

    Full Text Available Abstract Background The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer. Methods/Design The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain

  11. Corrosion Damage Investigation of Silver-Soldered Stainless Steel Orthodontic Appliances Used in Vivo / Ocena Zniszczeń Korozyjnych Używanych In Vivo Stałych Aparatów Ortodontycznych O Połączeniach Lutowanych Na Bazie Srebra

    Directory of Open Access Journals (Sweden)

    Łępicka M.

    2015-12-01

    Full Text Available Processes of destruction of products used in orthodontic treatment, e.g. fixed orthodontic appliances, microimplants or dental prostheses considerably limit its operational lifetime and comfort and safety of patients. The objective of the research was to evaluate and assess corrosion damage to silver-soldered stainless steel rapid palatal expansion Hyrax devices. Used in vivo for 2 or 6 months, respectively, RPE (rapid palatal expansion devices were analyzed macroscopically and in a scanning electron microscope with an energy X-ray analyzer for signs of corrosion. The evaluated appliances showed discernible differences between the overall condition of the noble solders and the stainless steel elements. The Ag-rich solders were chiefly covered in corrosion pits, whereas stainless steel wires, molar bands and Hyrax screws presented corrosion-free surfaces. What is more, the EDS analysis showed differential element composition of the solders. According to the results, noble materials, such as Ag-rich solders, can corrode in a salivary environment when coupled with stainless steel. The selective leaching processes are observed.

  12. Automated Verification of Quantum Protocols using MCMAS

    Directory of Open Access Journals (Sweden)

    F. Belardinelli

    2012-07-01

    Full Text Available We present a methodology for the automated verification of quantum protocols using MCMAS, a symbolic model checker for multi-agent systems The method is based on the logical framework developed by D'Hondt and Panangaden for investigating epistemic and temporal properties, built on the model for Distributed Measurement-based Quantum Computation (DMC, an extension of the Measurement Calculus to distributed quantum systems. We describe the translation map from DMC to interpreted systems, the typical formalism for reasoning about time and knowledge in multi-agent systems. Then, we introduce dmc2ispl, a compiler into the input language of the MCMAS model checker. We demonstrate the technique by verifying the Quantum Teleportation Protocol, and discuss the performance of the tool.

  13. SIP protocol model for OMNET++

    Directory of Open Access Journals (Sweden)

    Jan Kucerak

    2016-01-01

    Full Text Available The article describes our new SIP protocol implementation for the OMNeT++ simulation framework. OMNeT++ simulation framework provides an extensive support of IP related protocols, nevertheless a working SIP protocol implementation is missing. Real measurements were also done using a SIPp traffic generator and the results are compared to those obtained by our new SIP model. Since this work is a part of bigger project concerned strictly on measuring "first response times" over networks with a faulty transmission links, the actually collected statistics are focused only this way.

  14. Assessing the value of structured protocols for forensic interviews of alleged child abuse victims.

    Science.gov (United States)

    Orbach, Y; Hershkowitz, I; Lamb, M E; Sternberg, K J; Esplin, P W; Horowitz, D

    2000-06-01

    To evaluate the effectiveness of a structured interview protocol (NICHD Investigative Interview Protocol) operationalizing universally recommended guidelines for forensic interviews. The NICHD Investigative Protocol was designed to maximize the amount of information obtained using recall memory probes, which are likely to elicit more accurate information than recognition memory probes. Forensic investigators were trained to use the NICHD protocol while conducting feedback-monitored simulation interviews. The utility of the protocol was then evaluated by comparing 55 protocol interviews with 50 prior interviews by the same investigators, matched with respect to characteristics likely to affect the richness of the children's accounts. The comparison was based on an analysis of the investigators' utterance types, distribution, and timing, as well as quantitative and qualitative characteristics of the information produced. As predicted, protocol interviews contained more open-ended prompts overall as well as before the first option-posing utterance than non-protocol interviews did. More details were obtained using open-ended invitations and fewer were obtained using focused questions in protocol interviews than in non-protocol interviews, although the total number of details elicited did not differ significantly. In both conditions, older children provided more details than younger children did. The findings confirmed that implementation of professionally recommended practices affected the behavior of interviewers in both the pre-substantive and substantive phases of their interviews and enhanced the quality (i.e., likely accuracy) of information elicited from alleged victims.

  15. Effective cutoffs for detecting random, partially random, and nonrandom 350-item MMPI--a short form protocols.

    Science.gov (United States)

    Pinsoneault, Terry B

    2014-06-01

    The ability of the 350-item short form Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A; Butcher et al., 1992) validity scales to detect random protocols was investigated using samples of 250 nonrandom protocols, 250 half-random protocols, and 250 all-random protocols. As the manual warns, long form cutoffs of the Variable Response Inconsistency scale (VRIN) of 75T and the Infrequency scale (F) of 90T were ineffective in detecting random protocols. Alternative cutoffs for F₁ and the truncated VRIN and F scales were investigated. Short form subscales of VRIN and F were developed to improve detection of partially random protocols. An algorithm using alternative cutoffs for the scales and the new subscales was quite effective, detecting 95% of the all-random protocols, 87% of the half-random protocols, and 98% of the nonrandom protocols. A follow-up cross-validation study was conducted that confirmed the effectiveness of the algorithm.

  16. In vivo antimalarial and cytotoxic properties of Annona senegalensis ...

    African Journals Online (AJOL)

    The in vivo animal antimalarial and in vitro cytotoxic activities of the methanol extract of Annona senegalensis Pers. (Annonaceae) was investigated in this study. The in vivo antimalarial activity of the methanol extract against Plasmodium berghei was assessed using the 4-day suppressive test procedure. The extract of A.

  17. Nevomelanocytic atypia detection by in vivo reflectance confocal microscopy

    Directory of Open Access Journals (Sweden)

    Ingrida Vaišnorienė

    2014-01-01

    Conclusions: Nevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions.

  18. Static Validation of a Voting Protocol

    DEFF Research Database (Denmark)

    Nielsen, Christoffer Rosenkilde; Andersen, Esben Heltoft; Nielson, Hanne Riis

    2005-01-01

    The desired security properties of electronic voting protocols include verifiability, accuracy, democracy and fairness. In this paper we use a static program analysis tool to validate these properties for one of the classical voting protocols under appropriate assumptions. The protocol is formali......The desired security properties of electronic voting protocols include verifiability, accuracy, democracy and fairness. In this paper we use a static program analysis tool to validate these properties for one of the classical voting protocols under appropriate assumptions. The protocol...

  19. In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; van Gennip, Maria; Jakobsen, Tim H

    2010-01-01

    , with the aim of disabling the expression of virulence and reduction of antibiotic tolerance. Here we present protocols for screening and testing for acyl-homoserine lactone (AHL)-dependent QS inhibition. We also present protocols for the in vivo validation of QSIs as possible drug candidates. The presented...... methods allow the evaluation of QS inhibition by a potential drug candidate within 2-3 weeks....

  20. In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

    OpenAIRE

    Tang, Haiying; Vasselli, Joseph R.; Tong, Christopher; Heymsfield, Steven B.; Wu, Ed X.

    2009-01-01

    Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate t...

  1. The in vitro and in vivo comet assays.

    Science.gov (United States)

    Burlinson, Brian

    2012-01-01

    The strategy for testing for genotoxicity covers three main areas, namely gene mutation, chromosome aberration or breakage (clastogenicity), and chromosome loss or gain (aneuploidy). The current generalized strategy consists of assays capable of detecting all of these endpoints using in vitro assays such as the Ames test for detecting gene mutations in bacteria, the human peripheral lymphocyte chromosome aberration (CA) test for detecting clastogenicity, and the in vitro micronucleus test for clastogenicity and aneuploidy. The primary in vivo assay, and generally the only in vivo assay required, is the in vivo rodent bone marrow micronucleus assay. However, there are instances when these assays alone are inadequate and further testing is required, especially in vivo. Historically, the preferred second assay has been the rodent liver unscheduled DNA synthesis assay but recently this has been superseded by the rodent single cell gel electrophoresis or Comet assay. This assay has numerous advantages especially in vivo, where virtually any tissue can be examined. The status of the in vitro comet assay in regulatory testing is much less clear although a preliminary review of data from the assay has shown it to be more specific than other in vitro genotoxicity tests and less prone to false positives.Detailed here are general protocols for both the in vitro and in vivo comet assays which will form the basis of the pending OECD guideline for the assay.

  2. Antibody engineering: methods and protocols

    National Research Council Canada - National Science Library

    Chames, Patrick

    2012-01-01

    "Antibody Engineering: Methods and Protocols, Second Edition was compiled to give complete and easy access to a variety of antibody engineering techniques, starting from the creation of antibody repertoires and efficient...

  3. National Elk Refuge vaccination protocol

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Proposal by the State of Wyoming, Wyoming Game and Fish Department, to vaccinate elk on the National Elk Refuge. The proposal provides a protocol for vaccinating elk...

  4. Recommended protocols for sampling macrofungi

    Science.gov (United States)

    Gregory M. Mueller; John Paul Schmit; Sabine M. Hubndorf Leif Ryvarden; Thomas E. O' Dell; D. Jean Lodge; Patrick R. Leacock; Milagro Mata; Loengrin Umania; Qiuxin (Florence) Wu; Daniel L. Czederpiltz

    2004-01-01

    This chapter discusses several issues regarding reommended protocols for sampling macrofungi: Opportunistic sampling of macrofungi, sampling conspicuous macrofungi using fixed-size, sampling small Ascomycetes using microplots, and sampling a fixed number of downed logs.

  5. Automata-theoretic protocol programming

    NARCIS (Netherlands)

    Jongmans, Sung-Shik Theodorus Quirinus

    2016-01-01

    Parallel programming has become essential for writing scalable programs on general hardware. Conceptually, every parallel program consists of workers, which implement primary units of sequential computation, and protocols, which implement the rules of interaction that workers must abide by. As

  6. Towards in vivo focal cortical dysplasia phenotyping using quantitative MRI.

    Science.gov (United States)

    Adler, Sophie; Lorio, Sara; Jacques, Thomas S; Benova, Barbora; Gunny, Roxana; Cross, J Helen; Baldeweg, Torsten; Carmichael, David W

    2017-01-01

    Focal cortical dysplasias (FCDs) are a range of malformations of cortical development each with specific histopathological features. Conventional radiological assessment of standard structural MRI is useful for the localization of lesions but is unable to accurately predict the histopathological features. Quantitative MRI offers the possibility to probe tissue biophysical properties in vivo and may bridge the gap between radiological assessment and ex-vivo histology. This review will cover histological, genetic and radiological features of FCD following the ILAE classification and will explain how quantitative voxel- and surface-based techniques can characterise these features. We will provide an overview of the quantitative MRI measures available, their link with biophysical properties and finally the potential application of quantitative MRI to the problem of FCD subtyping. Future research linking quantitative MRI to FCD histological properties should improve clinical protocols, allow better characterisation of lesions in vivo and tailored surgical planning to the individual.

  7. Subclass of individual IgA-secreting human lymphocytes. Investigation of in vivo pneumococcal polysaccharide-induced and in vitro mitogen-induced blood B cells by monolayer plaque-forming cell assays

    DEFF Research Database (Denmark)

    Heilmann, C; Barington, T; Sigsgaard, T

    1988-01-01

    The subclass of individual human IgA B cells was investigated by means of monolayer plaque-forming cell assays permitting analysis of all IgA-secreting cells as well as of cells secreting IgA anti-pneumococcal polysaccharide antibody. Center cells were examined by indirect immunofluorescence...

  8. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

    Directory of Open Access Journals (Sweden)

    Aaron H Fronk

    2016-07-01

    Full Text Available The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included.

  9. High-wavenumber FT-Raman spectroscopy for in vivo and ex vivo measurements of breast cancer

    DEFF Research Database (Denmark)

    Garcia-Flores, A. F.; Raniero, L.; Canevari, R. A.

    2011-01-01

    The identification of normal and cancer breast tissue of rats was investigated using high-frequency (HF) FT-Raman spectroscopy with a near-infrared excitation source on in vivo and ex vivo measurements. Significant differences in the Raman intensities of prominent Raman bands of lipids and proteins...... structures (2,800-3,100 cm(-1)) as well as in the broad band of water (3,100-3,550 cm(-1)) were observed in mean normal and cancer tissue spectra. The multivariate statistical analysis methods of principal components analysis (PCA) and linear discriminant analysis (LDA) were performed on all high......-frequency Raman spectra of normal and cancer tissues. LDA results with the leave-one-out cross-validation option yielded a discrimination accuracy of 77.2, 83.3, and 100% for in vivo transcutaneous, in vivo skin-removed, and ex vivo biopsy HF Raman spectra. Despite the lower discrimination value for the in vivo...

  10. 21 CFR 812.25 - Investigational plan.

    Science.gov (United States)

    2010-04-01

    ... protocol describing the methodology to be used and an analysis of the protocol demonstrating that the investigation is scientifically sound. (c) Risk analysis. A description and analysis of all increased risks to which subjects will be exposed by the investigation; the manner in which these risks will be minimized...

  11. A protocol to analyse cellular dynamics during plant development.

    Science.gov (United States)

    de Reuille, Pierre Barbier; Bohn-Courseau, Isabelle; Godin, Christophe; Traas, Jan

    2005-12-01

    In vivo microscopy generates images that contain complex information on the dynamic behaviour of three-dimensional (3D) objects. As a result, adapted mathematical and computational tools are required to help in their interpretation. Ideally, a complete software chain to study the dynamics of a complex 3D object should include: (i) the acquisition, (ii) the preprocessing and (iii) segmentation of the images, followed by (iv) a reconstruction in time and space and (v) the final quantitative analysis. Here, we have developed such a protocol to study cell dynamics at the shoot apical meristem in Arabidopsis. The protocol uses serial optical sections made with the confocal microscope. It includes specially designed algorithms to automate the identification of cell lineage and to analyse the quantitative behaviour of the meristem surface.

  12. A Type Theoretic Investigation of the Verification of Voting Protocols

    DEFF Research Database (Denmark)

    Gustafsson, Daniel

    2016-01-01

    and calculation of probabilities, in particular ∑-types are used as they correspond to summation. Furthermore, I extend the type theory with process algebraic constructions in order to capture attack games as defined by semantic security in cryptography. To type these processes I propose a session type system...... the proofs used to justify both the correctness and security of such cryptographic constructions inside type theory. This requires a theory of probabilities in order to describe the probabilistic algorithms used. My contributions include, using types and type isomorphisms to simplify both specification...

  13. Quantifying drug-protein binding in vivo.

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, B; Bench, G; Keating III, G; Palmblad, M; Vogel, J; Grant, P G; Hillegonds, D

    2004-02-17

    Accelerator mass spectrometry (AMS) provides precise quantitation of isotope labeled compounds that are bound to biological macromolecules such as DNA or proteins. The sensitivity is high enough to allow for sub-pharmacological (''micro-'') dosing to determine macromolecular targets without inducing toxicities or altering the system under study, whether it is healthy or diseased. We demonstrated an application of AMS in quantifying the physiologic effects of one dosed chemical compound upon the binding level of another compound in vivo at sub-toxic doses [4].We are using tissues left from this study to develop protocols for quantifying specific binding to isolated and identified proteins. We also developed a new technique to quantify nanogram to milligram amounts of isolated protein at precisions that are comparable to those for quantifying the bound compound by AMS.

  14. Modeling and Verification of the Bitcoin Protocol

    Directory of Open Access Journals (Sweden)

    Kaylash Chaudhary

    2015-11-01

    Full Text Available Bitcoin is a popular digital currency for online payments, realized as a decentralized peer-to-peer electronic cash system. Bitcoin keeps a ledger of all transactions; the majority of the participants decides on the correct ledger. Since there is no trusted third party to guard against double spending, and inspired by its popularity, we would like to investigate the correctness of the Bitcoin protocol. Double spending is an important threat to electronic payment systems. Double spending would happen if one user could force a majority to believe that a ledger without his previous payment is the correct one. We are interested in the probability of success of such a double spending attack, which is linked to the computational power of the attacker. This paper examines the Bitcoin protocol and provides its formalization as an UPPAAL model. The model will be used to show how double spending can be done if the parties in the Bitcoin protocol behave maliciously, and with what probability double spending occurs.

  15. Frequency bands and spatiotemporal dynamics of beta burst stimulation induced afterdischarges in hippocampus in vivo.

    Science.gov (United States)

    Mikkonen, J E; Penttonen, M

    2005-01-01

    Temporal and spatial characteristics of hippocampal neuronal network activation are modified during epileptiform afterdischarges. We developed a beta burst stimulation protocol to investigate subregional variations and substrates of rhythmic population spike discharges in vivo in urethane anesthetized Wistar rat hippocampus with a 14-electrode recording array and extracellular single electrode recordings. Our 64 pulse beta burst stimulation protocol was constructed from electrical pulses delivered at intervals corresponding to beta (14-25 Hz), Delta (2 Hz), and slow (0.5 Hz) frequencies. In each experiment these interleaved pulses were all repeated four times with unchanged intervals. Stimulation of either perforant path or fimbria fornix induced a prolonged afterdischarge pattern peaking at 200 Hz fast, 20 Hz beta, and 2 Hz Delta frequencies. Analysis of variance confirmed that the response pattern of the discharges remained constant regardless of the stimulation beta frequency. Within the afterdischarge the fast frequencies were restricted to independent hippocampal subfields whereas beta and slow frequencies correlated across the subfields. Current source density (CSD) analysis revealed that the original signal propagation through subfields of the hippocampus was compromised during the beta burst stimulation induced afterdischarge. In addition, the CSD profile of the epileptiform afterdischarge was consistently similar across the different experiments. Time-frequency analysis revealed that the beta frequency afterdischarge was initiated and terminated at higher gamma (30-80 Hz) frequencies. However, the alterations in the CSD profile of the hippocampus coincided with the beta frequency dominated discharges. We propose that hippocampal epileptiform activity at fast, beta and Delta frequencies represents coupled oscillators at respectively increasing spatial scales in the hippocampal neuronal network in vivo.

  16. In-vivo

    Science.gov (United States)

    Zhu, Timothy C; Kim, Michele M; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

    2015-02-01

    Dosimetry of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [ 1 O 2 ] rx,sh , for PDT was developed. An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [ 1 O 2 ] rx,sh . Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin ® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. The mean values (standard deviation) of the in-vivo [ 1 O 2 ] rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×10 7 and 4.6×10 7 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin ® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g , β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. In comparison, the [ 1 O 2 ] rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×10 8 per cell per 1/ e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/ e to in-vivo singlet

  17. Solid phase microextraction fills the gap in tissue sampling protocols.

    Science.gov (United States)

    Bojko, Barbara; Gorynski, Krzysztof; Gomez-Rios, German Augusto; Knaak, Jan Matthias; Machuca, Tiago; Spetzler, Vinzent Nikolaus; Cudjoe, Erasmus; Hsin, Michael; Cypel, Marcelo; Selzner, Markus; Liu, Mingyao; Keshavjee, Shaf; Pawliszyn, Janusz

    2013-11-25

    Metabolomics and biomarkers discovery are an integral part of bioanalysis. However, untargeted tissue analysis remains as the bottleneck of such studies due to the invasiveness of sample collection, as well as the laborious and time-consuming sample preparation protocols. In the current study, technology integrating in vivo sampling, sample preparation and global extraction of metabolites--solid phase microextraction was presented and evaluated during liver and lung transplantation in pig model. Sampling approaches, including selection of the probe, transportation, storage conditions and analyte coverage were discussed. The applicability of the method for metabolomics studies was demonstrated during lung transplantation experiments. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Evaluation of ribonucleic acid amplification protocols for human oocyte transcriptome analysis

    NARCIS (Netherlands)

    Mantikou, Eleni; Bruning, Oskar; Mastenbroek, Sebastiaan; Repping, Sjoerd; Breit, Timo Markus; de Jong, Mark

    2016-01-01

    To develop a reliable, reproducible, and sensitive method for investigating gene-expression profiles from individual human oocytes. Five commercially available protocols were investigated for their efficiency to amplify messenger RNA (mRNA) from 54 single human oocytes. Protocols resulting in

  19. Evaluation of ribonucleic acid amplification protocols for human oocyte transcriptome analysis

    NARCIS (Netherlands)

    Mantikou, E.; Bruning, O.; Mastenbroek, S.; Repping, S.; Breit, T.M.; de Jong, M.

    2015-01-01

    OBJECTIVE: To develop a reliable, reproducible, and sensitive method for investigating gene-expression profiles from individual human oocytes. DESIGN: Five commercially available protocols were investigated for their efficiency to amplify messenger RNA (mRNA) from 54 single human oocytes. Protocols

  20. In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

    KAUST Repository

    Mächler, Philipp

    2015-11-19

    Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons. © 2016 Elsevier Inc.

  1. A comparison between equations describing in vivo MT: the effects of noise and sequence parameters.

    Science.gov (United States)

    Cercignani, Mara; Barker, Gareth J

    2008-04-01

    Quantitative models of magnetization transfer (MT) allow the estimation of physical properties of tissue which are thought to reflect myelination, and are therefore likely to be useful for clinical application. Although a model describing a two-pool system under continuous wave-saturation has been available for two decades, generalizing such a model to pulsed MT, and therefore to in vivo applications, is not straightforward, and only recently have a range of equations predicting the outcome of pulsed MT experiments been proposed. These solutions of the 2-pool model are based on differing assumptions and involve differing degrees of complexity, so their individual advantages and limitations are not always obvious. This paper is concerned with the comparison of three differing signal equations. After reviewing the theory behind each of them, their accuracy and precision is investigated using numerical simulations under variable experimental conditions such as degree of T1-weighting of the acquisition sequence and SNR, and the consistency of numerical results is tested using in vivo data. We show that while in conditions of minimal T1-weighting, high SNR, and large duty cycle the solutions of the three equations are consistent, they have a different tolerance to deviations from the basic assumptions behind their development, which should be taken into account when designing a quantitative MT protocol.

  2. 2014 Building America House Simulation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Engebrecht-Metzger, C. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Horowitz, S. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hendron, R. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-03-01

    As BA has grown to include a large and diverse cross-section of the home building and retrofit industries, it has become more important to develop accurate, consistent analysis techniques to measure progress towards the program's goals. The House Simulation Protocol (HSP) document provides guidance to program partners and managers so they can compare energy savings for new construction and retrofit projects. The HSP provides the program with analysis methods that are proven to be effective and reliable in investigating the energy use of advanced energy systems and of entire houses.

  3. 2014 Building America House Simulation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, E. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Engebrecht, C. Metzger [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Horowitz, S. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hendron, R. [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2014-03-01

    As Building America has grown to include a large and diverse cross-section of the home building and retrofit industries, it has become more important to develop accurate, consistent analysis techniques to measure progress towards the program's goals. The House Simulation Protocol (HSP) document provides guidance to program partners and managers so they can compare energy savings for new construction and retrofit projects. The HSP provides the program with analysis methods that are proven to be effective and reliable in investigating the energy use of advanced energy systems and of entire houses.

  4. Observing documentary reading by verbal protocol

    Directory of Open Access Journals (Sweden)

    Fujita Mariangela Spotti Lopes

    2003-01-01

    Full Text Available Verifies the applicability to research on indexers' reading strategies of the process observing technique known as Verbal Protocol or Thinking Aloud. This interpretative-qualitative data collecting technique allows the observation of different kinds of process during the progress of different kinds of tasks. Presents a theoretical investigation into "reading" and into formal methodological procedures to observe reading processes. Describes details of the methodological procedures adopted in five case studies with analysis of samples of data. The project adopted three kinds of parameters for data analysis: theoretical, normative, empirical (derived from observations made in the first case study. The results are compared, and important conclusions regarding documentary reading are drawn.

  5. Superselection rules and quantum protocols

    Science.gov (United States)

    Kitaev, Alexei; Mayers, Dominic; Preskill, John

    2004-05-01

    We show that superselection rules do not enhance the information-theoretic security of quantum cryptographic protocols. Our analysis employs two quite different methods. The first method uses the concept of a reference system—in a world subject to a superselection rule, unrestricted operations can be simulated by parties who share access to a reference system with suitable properties. By this method, we prove that if an n -party protocol is secure in a world subject to a superselection rule, then the security is maintained even if the superselection rule is relaxed. However, the proof applies only to a limited class of superselection rules, those in which the superselection sectors are labeled by unitary irreducible representations of a compact symmetry group. The second method uses the concept of the format of a message sent between parties—by verifying the format, the recipient of a message can check whether the message could have been sent by a party who performed charge-conserving operations. By this method, we prove that protocols subject to general superselection rules (including those pertaining to non-Abelian anyons in two dimensions) are no more secure than protocols in the unrestricted world. However, the proof applies only to two-party protocols. Our results show in particular that, if no assumptions are made about the computational power of the cheater, then secure quantum bit commitment and strong quantum coin flipping with arbitrarily small bias are impossible in a world subject to superselection rules.

  6. Embedded Network Protocols for Mobile Devices

    Science.gov (United States)

    Galataki, Despo; Radulescu, Andrei; Verstoep, Kees; Fokkink, Wan

    Embedded networks for chip-to-chip networks are emerging as communication infrastructure in mobile devices. We present three novel embedded network protocols: a sliding window protocol, a protocol for opening and closing connections, and a bandwidth reservation protocol. The design of these protocols is tailored to the low power and low cost requirements of mobile devices. The model checker SPIN played an important role in the design and analysis of these protocols. Large instances of the protocols could be analyzed successfully using the distributed model checker DiVinE.

  7. Multi-party quantum key agreement protocol secure against collusion attacks

    Science.gov (United States)

    Wang, Ping; Sun, Zhiwei; Sun, Xiaoqiang

    2017-07-01

    The fairness of a secure multi-party quantum key agreement (MQKA) protocol requires that all involved parties are entirely peer entities and can equally influence the outcome of the protocol to establish a shared key wherein no one can decide the shared key alone. However, it is found that parts of the existing MQKA protocols are sensitive to collusion attacks, i.e., some of the dishonest participants can collaborate to predetermine the final key without being detected. In this paper, a multi-party QKA protocol resisting collusion attacks is proposed. Different from previous QKA protocol resisting N-1 coconspirators or resisting 1 coconspirators, we investigate the general circle-type MQKA protocol which can be secure against t dishonest participants' cooperation. Here, t < N. We hope the results of the presented paper will be helpful for further research on fair MQKA protocols.

  8. Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.

    Science.gov (United States)

    Zhu, Hong; Kochevar, Irene E; Behlau, Irmgard; Zhao, Jie; Wang, Fenghua; Wang, Yucheng; Sun, Xiaodong; Hamblin, Michael R; Dai, Tianhong

    2017-01-01

    To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

  9. In vivo measurement of surgical gestures.

    Science.gov (United States)

    Dubois, Patrick; Thommen, Quentin; Jambon, Anne Claire

    2002-01-01

    Virtual reality techniques are now more and more widely used in the field of surgical training. However, the realism of the simulation devices requires a good knowledge of the mechanical behavior of the living organs. To provide perioperative measurement of laparoscopic surgical operations, we equipped a conventional operating grasper with a force sensor and a position sensor. The entire apparatus was connected to a PC that controlled the real-time data acquisition. After calibrating the sensors, we conducted three series of in vivo measurements on animals under video control. A standardized protocol was set up to perform various surgical gestures in a reproducible manner. Under these conditions, we can assess an original tool for a quantitative approach of surgical gestures' mechanics. The preliminary results will be extended by measurements during other operations and with other surgical instruments. The in vivo quantification of the mechanical interactions between operating instruments and anatomical structures is of great interest for the introduction of the force feedback in virtual surgery, for the modeling of the mechanical behavior of living organs, and for the design of new surgical instruments. This quantification of manipulations opens new prospects in the evaluation of surgical practices.

  10. Developing security protocols in χ-Spaces

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Milicia, Giuseppe

    2002-01-01

    It is of paramount importance that a security protocol effectively enforces the desired security requirements. The apparent simplicity of informal protocol descriptions hides the inherent complexity of their interactions which, often, invalidate informal correctness arguments and justify the effort......-Spaces aids several steps in the development of a security protocolprotocol executions can be simulated in hostile environments, a security protocol can be implemented, and security properties of implementations can be formally verified....

  11. Distance hijacking attacks on distance bounding protocols

    OpenAIRE

    Cremers, Cas; Rasmussen, Kasper Bonne; Čapkun, Srdjan

    2011-01-01

    Distance bounding protocols are typically analyzed with respect to three types of attacks: Distance Fraud, Mafia Fraud, and Terrorist Fraud. We define and analyze a fourth main type of attack on distance bounding protocols, called Distance Hijacking. We show that many proposed distance bounding protocols are vulnerable to this type of attack, and we propose solutions to make these protocols resilient to Distance Hijacking. We further show that verifying distance bounding protocols using exist...

  12. On the Correctness of Sliding Window Protocols

    OpenAIRE

    van de Snepscheut, Jan L.A.

    1991-01-01

    In this note some struggles with the sliding window protocol and the special case known as the alternating bit protocol, are reported. We try to give a correctness proof, and discover that we cannot do so for one of the versions of the sliding window protocol. One may either require channels that satisfy stronger assumptions or, as we will do, adapt the protocol and stick to the weaker assumptions. The alternating bit protocol can be traced back to [Bartlett]. We have been unab...

  13. Superposition Attacks on Cryptographic Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Funder, Jakob Løvstad; Nielsen, Jesper Buus

    2011-01-01

    string model. While our protocol is classical, it is sound against a cheating unbounded quantum prover and computational zero-knowledge even if the verifier is allowed a superposition attack. Finally, we consider multiparty computation and show that for the most general type of attack, simulation based......Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece...... of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security...

  14. Development, Validity and Reliability of the Londrina Activities of Daily Living Protocol for Subjects With COPD.

    Science.gov (United States)

    Sant'Anna, Thaís; Donária, Leila; Furlanetto, Karina C; Morakami, Fernanda; Rodrigues, Antenor; Grosskreutz, Talita; Hernandes, Nidia A; Gosselink, Rik; Pitta, Fabio

    2017-03-01

    To avoid symptoms, patients with COPD may reduce the amount of activities of daily living (ADL). Therefore, the aim of the present study was to develop a standardized protocol to evaluate ADL performance in subjects with COPD (Londrina ADL protocol) and to assess the validity and reliability of the protocol in this population. The Londrina ADL protocol was created based on activities included in previous studies aimed at investigating outcomes from ADL. Activities were included in the protocol because they could represent other activities of similar patterns and because they could be actually performed, not simulated. Twenty subjects with COPD (12 men, 70 ± 7 y old, FEV1 = 54 ± 15% predicted) wore 2 motion sensors while performing the protocol 4 times, 2 of them wearing a portable gas analyzer. Subjects were also submitted to assessments of lung function, functional exercise capacity, functional status, impact on health status, and physical activity in daily life. The Londrina ADL protocol comprised of 5 activities representing ADL, involving upper limbs, lower limbs, and trunk movements. Londrina ADL protocol duration presented high values of intraclass correlation coefficient, even using a mask for gas analysis (intraclass correlation coefficient >0.90, P < .001). Intensity of movement during the protocol performance was highly correlated to intensity of movement in daily life (r = 0.71). The protocol duration was correlated with functional status and impact on health status variables from questionnaires (0.36 ≤ r ≤ 0.59). There was also correlation between functional exercise capacity and the protocol duration (r = -0.64). The Londrina ADL protocol was a valid and reliable protocol to evaluate ADL performance in subjects with COPD. It is a protocol that can be used in clinical practice and in future studies to investigate ADL outcomes, including those studies that require gas analysis and the wearing of a mask. Copyright © 2017 by Daedalus Enterprises.

  15. Quercetin glycosides and chlorogenic acid in highbush blueberry leaf decoction prevent cataractogenesis in vivo and in vitro: Investigation of the effect on calpains, antioxidant and metal chelating properties.

    Science.gov (United States)

    Ferlemi, Anastasia-Varvara; Makri, Olga E; Mermigki, Penelope G; Lamari, Fotini N; Georgakopoulos, Constantinos D

    2016-04-01

    The present study investigates whether highbush blueberry leaf polyphenols prevent cataractogenesis and the underlying mechanisms. Chlorogenic acid, quercetin, rutin, isoquercetin and hyperoside were quantified in Vaccinium corymbosum leaf decoction (BBL) using HPLC-DAD. Wistar rats were injected subcutaneously with 20 μmol selenite (Na2SeO3)/kg body weight on postnatal (PN) day 10 (Se, n = 8-10/group) only or also intraperitoneally with 100 mg dry BBL/kg body weight on PN days 11 and 12 (SeBBL group, n = 10). Control group received only normal saline (C). Cataract evaluation revealed that BBL significantly prevented lens opacification. It, also, protected lens from selenite oxidative attack and prevented calpain activation, as well as protein loss and aggregation. In vitro studies showed that quercetin attenuated porcine lens turbidity caused by [Formula: see text] or Ca(2+) and interacted efficiently with those ions according to UV-Vis titration experiments. Finally, rutin, isoquercetin and hyperoside moderately inhibited pure human μ-calpain. Conclusively, blueberry leaf extract, a rich source of bioactive polyphenols, prevents cataractogenesis by their strong antioxidant, chelating properties and through direct/indirect inhibition of lens calpains. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The Kyoto protocol development; La viabilite du protocole de Kyoto

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, R. [Harvard Univ., Barrow, AK (United States); Guesneris, R. [College de France, 75 - Paris (France)

    2002-04-01

    From the author R. Cooper point of view the Kyoto Protocol is a flawed concept. The reasons for dropping Kyoto are presented in this paper insisting that rejecting Kyoto not means to imply that global climate change is not a serious problem. After a presentation of the US policy facing the Climatic Change, some concluding propositions are proposed. (A.L.B.)

  17. National protocol framework for the inventory and monitoring of bees

    Science.gov (United States)

    Droege, Sam; Engler, Joseph D.; Sellers, Elizabeth A.; Lee O'Brien,

    2016-01-01

    This national protocol framework is a standardized tool for the inventory and monitoring of the approximately 4,200 species of native and non-native bee species that may be found within the National Wildlife Refuge System (NWRS) administered by the U.S. Fish and Wildlife Service (USFWS). However, this protocol framework may also be used by other organizations and individuals to monitor bees in any given habitat or location. Our goal is to provide USFWS stations within the NWRS (NWRS stations are land units managed by the USFWS such as national wildlife refuges, national fish hatcheries, wetland management districts, conservation areas, leased lands, etc.) with techniques for developing an initial baseline inventory of what bee species are present on their lands and to provide an inexpensive, simple technique for monitoring bees continuously and for monitoring and evaluating long-term population trends and management impacts. The latter long-term monitoring technique requires a minimal time burden for the individual station, yet can provide a good statistical sample of changing populations that can be investigated at the station, regional, and national levels within the USFWS’ jurisdiction, and compared to other sites within the United States and Canada. This protocol framework was developed in cooperation with the United States Geological Survey (USGS), the USFWS, and a worldwide network of bee researchers who have investigated the techniques and methods for capturing bees and tracking population changes. The protocol framework evolved from field and lab-based investigations at the USGS Bee Inventory and Monitoring Laboratory at the Patuxent Wildlife Research Center in Beltsville, Maryland starting in 2002 and was refined by a large number of USFWS, academic, and state groups. It includes a Protocol Introduction and a set of 8 Standard Operating Procedures or SOPs and adheres to national standards of protocol content and organization. The Protocol Narrative

  18. Symbolic Analysis of Cryptographic Protocols

    DEFF Research Database (Denmark)

    Dahl, Morten

    We present our work on using abstract models for formally analysing cryptographic protocols: First, we present an ecient method for verifying trace-based authenticity properties of protocols using nonces, symmetric encryption, and asymmetric encryption. The method is based on a type system...... of Gordon et al., which we modify to support fully-automated type inference. Tests conducted via an implementation of our algorithm found it to be very ecient. Second, we show how privacy may be captured in a symbolic model using an equivalencebased property and give a formal denition. We formalise...

  19. Protocols of myocardial perfusion SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Min [College of Medicine, Chungnam National University, Daejeon (Korea, Republic of)

    2005-02-15

    In myocardial perfusion scintigraphy, the results of this evaluation now confront the practitioner of nuclear medicine with methodological options. Most nuclear cardiologic studies are performed using thallium-201, Tc-99m sestamibi and Tc-99m tertrofosmin. Some part of these studies use some form of pharmacologic stress test. While tailoring each test to the individual is ideal, this may be impractical for a busy department. Accordingly, established protocols to be used for patients with similar clinical presentations will be helpful. The following review presents methodology of various imaging protocols mainly according to the guidelines of nuclear cardiology procedures in American Society of Nuclear Cardiology.

  20. Development of Uniform Protocol for Alopecia Areata Clinical Trials.

    Science.gov (United States)

    Solomon, James A

    2015-11-01

    Developing a successful treatment for alopecia areata (AA), clearly has not been at the forefront of the agenda for new drug/device development among the pharmaceutical and medical device industry. The National Alopecia Areata Foundation (NAAF), a patient advocacy group, initiated a plan to facilitate and drive clinical research toward finding safe and efficacious treatments for AA. As such, Alopecia Areata Uniform Protocols for clinical trials to test new treatments for AA were developed. The design of the uniform protocol is to accomplish the development of a plug-and-play template as well as to provide a framework wherein data from studies utilizing the uniform protocol can be compared through consistency of inclusions/exclusions, safety, and outcome assessment measures. A core uniform protocol for use by pharmaceutical companies in testing proof of concept for investigational products to treat AA. The core protocol includes standardized title, informed consent, inclusion/exclusion criteria, disease outcome assessments, and safety assessments. The statistical methodology to assess successful outcomes will also be standardized. The protocol as well as the informed consent form has been approved in concept by Liberty IRB and is ready to present to pharmaceutical companies.

  1. Inconsistent Reporting Between Meta-analysis Protocol and Publication - A Cross-Sectional Study.

    Science.gov (United States)

    Delgado, Alberto Falk; Delgado, Anna Falk

    2017-09-01

    Inconsistent reporting in published meta-analyses compared to registered protocol are poorly understood. The aim of the study was to assess inconsistencies between registered protocols and published reports among oncology drug meta-analyses. A cross-sectional study was performed including oncology drug meta-analyses published between January 1st and November 14th 2016 with a published protocol. Two investigators extracted data on: selection criteria, outcome(s) and statistical plan in protocol and manuscript, plus self-acknowledgement of inconsistent reporting between protocol and publication. Protocol registration was present in 19% (23/119) of all oncology drug meta-analyses. In meta-analyses with protocol (n=23), 70% (16/23) had issues with inconsistent reporting between protocol and published report concerning; inclusion criteria, comparator group, intervention, outcome (PICO) or statistical analysis. Self-acknowledgement of changes between protocol and publication was found in 50% (8/16). In meta-analyses with protocol, discrepancies between registered protocols and publications are frequent. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Capsiate supplementation reduces oxidative cost of contraction in exercising mouse skeletal muscle in vivo.

    Directory of Open Access Journals (Sweden)

    Kazuya Yashiro

    Full Text Available Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control or purified capsiate (at 10- or 100-mg/kg body weight on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR imaging and 31-phosphorus MR spectroscopy (31P-MRS. Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz, both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.

  3. A Comprehensive Survey on Hierarchical-Based Routing Protocols for Mobile Wireless Sensor Networks: Review, Taxonomy, and Future Directions

    Directory of Open Access Journals (Sweden)

    Nabil Sabor

    2017-01-01

    Full Text Available Introducing mobility to Wireless Sensor Networks (WSNs puts new challenges particularly in designing of routing protocols. Mobility can be applied to the sensor nodes and/or the sink node in the network. Many routing protocols have been developed to support the mobility of WSNs. These protocols are divided depending on the routing structure into hierarchical-based, flat-based, and location-based routing protocols. However, the hierarchical-based routing protocols outperform the other routing types in saving energy, scalability, and extending lifetime of Mobile WSNs (MWSNs. Selecting an appropriate hierarchical routing protocol for specific applications is an important and difficult task. Therefore, this paper focuses on reviewing some of the recently hierarchical-based routing protocols that are developed in the last five years for MWSNs. This survey divides the hierarchical-based routing protocols into two broad groups, namely, classical-based and optimized-based routing protocols. Also, we present a detailed classification of the reviewed protocols according to the routing approach, control manner, mobile element, mobility pattern, network architecture, clustering attributes, protocol operation, path establishment, communication paradigm, energy model, protocol objectives, and applications. Moreover, a comparison between the reviewed protocols is investigated in this survey depending on delay, network size, energy-efficiency, and scalability while mentioning the advantages and drawbacks of each protocol. Finally, we summarize and conclude the paper with future directions.

  4. In vivo charge injection limits increased after 'unsafe' stimulation

    DEFF Research Database (Denmark)

    Meijs, Suzan; Sørensen, Søren; Rechendorff, Kristian

    2015-01-01

    was not observed with any of the stimulation protocols and no tissue damage was observed for the 20 mA – 200 Hz stimulation group. This indicates that the ‘safe potential window’ may not be applicable in vivo, as no damage was done stimulating with 20 mA at 200 Hz, while damage was done using the same current...

  5. [Investigation on the migration and biologic effects of nano FeOx powders under the exposure of extremely low frequency altering electric magnetic field in human heptoma-bearing nude mice in vivo].

    Science.gov (United States)

    Ju, Hui-Xiang; Dai, Zhen-Yu; Sun, Ming-Zhong

    2011-08-01

    To investigate the mechanism and biologic effects of 37 nm magnetic nano FeOx powders (MNPs) on human hepatoma-bearing nude mice. 37 nm MNPs were prepared by coprecipitation methods and then injected into human hepatoma (Bel-7402) bearing-nude mice through the tail vein. After injection of MNPs, the mice were first exposed under static magnetic field and then treated under extremely low frequency altering-electric magnetic field directing to the tumor area. The migration and trafficking of MNPs were determined by MMR. Tumor growth was monitored with calipers every 5 days and tumor volume was calculated on the basis of three-dimensioned measurements. The apoptosis of tumor cells was analyzed by flow cytometry analysis. The expressions of apoptosis-associated proteins Bcl-2, Bax and HSP27 were determined using western-blot analysis. Static magnetic field could direct the migration and trafficking of MNPs to the tumor site with a higher ratio of 98.9%. Extremely Low Frequency Electric-Magnetic Field (EMF) treatment could inhibit the proliferation of tumor cells and prolong the survive time of tumor-bearing mice injected with MNPs. In addition, the survival time of tumor-bearing mice and percentages of prohibition on tumor cell growth were 27.4+/-0.7 days and 37.5+/-0.8% (F = 0.005, P is less than to 0.05), respectively. The results of flow cytometry analyses showed that about 18.1+/-0.6% (F = 0.030, P is less than to 0.05) of tumor cells were induced into early apoptosis. Furthermore, expressions of apoptosis-associated proteins Bcl-2 and Bax were significantly induced by MNPs under EMF treatment. The ratio of Bcl/Bax in both MNPs and EMF treatment group was 0.07+/-0.01, which was much lower than that of control group (0.23+/-0.02) (F = 0.016, P is less than to 0.05). Heat shock protein-27 (Hsp-27) was not significantly induced in different treatment groups. Injection of MNPs with EMF exposure on human hepatoma-bearing nude mice could significantly prolong the

  6. In vivo and in vitro testing for selenium and selenium compounds bioavailability assessment in foodstuff.

    Science.gov (United States)

    Moreda-Piñeiro, Jorge; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

    2017-03-04

    The assessment of selenium and selenium species bioavailability in foodstuff is of special concern on the context of human nutrition. In vivo (human and animal), and in vitro tests are important approaches for estimating the bioavailability of toxic and essential compounds to humans. An overview on in vivo and in vitro bioavailability assays for releasing selenium and selenium species in foodstuffs is summarized. Se and Se species content in a foodstuff critically influence Se bioavailability and bioactivity to humans and animals. Se bioavailability is affected by foodstuff-matrix major composition and minor components. Foodstuffs processing and/or treatments could enhancement or decrease Se bioavailability. Experimental conditions such as the selection of healthy status of examined people (in in vivo humans approaches), the selection of animal model (in vivo animals approaches), or the selection of GI conditions (in in vitro tests) could determines the results. Thus, international standardized protocol for in vivo and in vitro approaches assessment is mandatory.

  7. In vitro-in vivo correlation in skin permeation.

    Science.gov (United States)

    Mohammed, D; Matts, P J; Hadgraft, J; Lane, M E

    2014-02-01

    In vitro skin permeation studies have been used extensively in the development and optimisation of delivery of actives in vivo. However, there are few reported correlations of such in vitro studies with in vivo data. The aim of this study was to investigate the skin permeation of a model active, niacinamide, both in vitro and in vivo. Conventional diffusion cell studies were conducted in human skin to determine niacinamide permeation from a range of vehicles which included dimethyl isosorbide (DMI), propylene glycol (PG), propylene glycol monolaurate (PGML), N-methyl 2-pyrrolidone (NMP), Miglyol 812N® (MG), and mineral oil (MO). Single, binary or ternary systems were examined. The same vehicles were subsequently examined to investigate niacinamide delivery in vivo. For this proof-of-concept study one donor was used for the in vitro studies and one volunteer for the in vivo investigations to minimise biovariability. Analysis of in vitro samples was conducted using HPLC and in vivo uptake of niacinamide was evaluated using Confocal Raman spectroscopy (CRS). The amount of niacinamide permeated through skin in vitro was linearly proportional to the intensity of the niacinamide signal determined in the stratum corneum in vivo. A good correlation was observed between the signal intensities of selected vehicles and niacinamide signal intensity. The findings provide further support for the use of CRS to monitor drug delivery into and across the skin. In addition, the results highlight the critical role of the vehicle and its disposition in skin for effective dermal delivery.

  8. Design and specification of the Xpress transfer high-speed protocol

    OpenAIRE

    Sacha, David Joseph

    1993-01-01

    Approved for public release, distribution is unlimited The use of fiber optics in high-speed data networks has significantly increased throughput and reliability at the physical layer. Consequently, the transport layer has become a bottleneck to the data transfer potential of highspeed networks. This bottleneck has forced an investigation of transport protocols and standards to be used in future networks. The Xpress Transfer Protocol (XTP) is a transport layer protocol designed to perform ...

  9. Performance Evaluation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Curti, Michele

    2005-01-01

    We use a special operational semantics which drives us in inferring quantitative measures on systems describing cryptographis cryptographic protocols. We assign rates to transitions by only looking at these labels. The rates reflect the distributed architecture running applications and the use of...... of possibly different cryptosystems. We then map transition systems to Markov chains and evaluate performance of systems, using standard tools....

  10. Improving the DGK comparison protocol

    NARCIS (Netherlands)

    Veugen, P.J.M.

    2012-01-01

    When processing signals in the encrypted domain, homomorphic encryption can be used to enable linear operations on encrypted data. Comparison of encrypted data however requires an additional protocol between the parties and will be relatively expensive. A well-known and frequently used comparison

  11. Protocol Natuurplan voor biologische landbouwbedrijven.

    NARCIS (Netherlands)

    Smeding, F.W.

    1996-01-01

    The Protocol Nature Plan is a step by step approach leading to the design of a Nature Plan for a biological farm. The aim is to increase nature values and ecological relationships on the farm. Research results are translated into easy practical measures

  12. Recursive Ping-Pong Protocols

    DEFF Research Database (Denmark)

    Huttel, Hans; Srba, Jiri

    2004-01-01

    This paper introduces a process calculus with recursion which allows us to express an unbounded number of runs of the ping-pong protocols introduced by Dolev and Yao. We study the decidability issues associated with two common approaches to checking security properties, namely reachability analysis...

  13. Affinity biosensors: techniques and protocols

    National Research Council Canada - National Science Library

    Rogers, Kim R; Mulchandani, Ashok

    1998-01-01

    ..., and government to begin or expand their biosensors research. This volume, Methods in Biotechnology vol. 7: Affinity Biosensors: Techniques and Protocols, describes a variety of classical and emerging transduction technologies that have been interfaced to bioaffinity elements (e.g., antibodies and receptors). Some of the reas...

  14. Bundle Security Protocol for ION

    Science.gov (United States)

    Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

    2011-01-01

    This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

  15. Cognitive Communications Protocols for SATCOM

    Science.gov (United States)

    2017-10-20

    during distributed transmit beamforming. We may, for example, assume that cooperative nodes are satellites in specific orbits with known velocities...communications protocols for satellite and space communications with possible broad applications in defense, homeland-security as well as consumer...form a foundation for achieving effective spectrum coexistence, interoperability and improved reliability in satellite transceivers in the presence of

  16. Utilizing high throughput screening data for predictive toxicology models: protocols and application to MLSCN assays

    Science.gov (United States)

    Guha, Rajarshi; Schürer, Stephan C.

    2008-06-01

    Computational toxicology is emerging as an encouraging alternative to experimental testing. The Molecular Libraries Screening Center Network (MLSCN) as part of the NIH Molecular Libraries Roadmap has recently started generating large and diverse screening datasets, which are publicly available in PubChem. In this report, we investigate various aspects of developing computational models to predict cell toxicity based on cell proliferation screening data generated in the MLSCN. By capturing feature-based information in those datasets, such predictive models would be useful in evaluating cell-based screening results in general (for example from reporter assays) and could be used as an aid to identify and eliminate potentially undesired compounds. Specifically we present the results of random forest ensemble models developed using different cell proliferation datasets and highlight protocols to take into account their extremely imbalanced nature. Depending on the nature of the datasets and the descriptors employed we were able to achieve percentage correct classification rates between 70% and 85% on the prediction set, though the accuracy rate dropped significantly when the models were applied to in vivo data. In this context we also compare the MLSCN cell proliferation results with animal acute toxicity data to investigate to what extent animal toxicity can be correlated and potentially predicted by proliferation results. Finally, we present a visualization technique that allows one to compare a new dataset to the training set of the models to decide whether the new dataset may be reliably predicted.

  17. In vivo toxicity study of Lantana camara

    OpenAIRE

    Badakhshan Mahdi Pour; Sreenivasan Sasidharan

    2011-01-01

    Objective: To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. Methods: The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results: All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions: Methanolic...

  18. Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells.

    Science.gov (United States)

    Kegel, Victoria; Deharde, Daniela; Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

    2016-03-30

    Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine(1). Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models.

  19. In vitro and in vivo evaluation of lyophilized bovine bone biocompatibility

    Directory of Open Access Journals (Sweden)

    Carlos Roberto Galia

    2008-01-01

    Full Text Available INTRODUCTION: The use of bone grafts in orthopedic, maxillofacial and dental surgery has been growing. Nevertheless, both fresh autografts and frozen allografts have limitations, and therefore, alternative synthetic or natural biomaterials, such as processed and lyophilized bovine bone graft have been developed. OBJECTIVE: To evaluate in vitro and in vivo biocompatibility of lyophilized bovine bone manufactured in a semi-industrial scale, according to a modifical protocol developed by the authors. METHODS: Samples of bovine cancellous bone were processed according to a protocol developed by Kakiuchi et al., and modified to process samples of bovine cancellous bone. The following trials were performed: in vitro cytotoxicity, in vivo acute systemic toxicity, in vivo oral irritation potential, in vitro pyrogenic reaction, and bioburden. RESULTS: The in vitro evaluation of lyophilized bovine cancellous bone revealed an absence of cytotoxicity in 100% of the samples. Regarding in vivo evaluation of acute systemic toxicity, neither macroscopic abnormalities nor deaths were noted in the animals. Pyrogenicity was not greater than 0.125 UE/ml in any of the samples. The bioburden revealed negative results for microbial growth before sterilization. Regarding the oral irritation potential, in vivo evaluation at 24 and 72 hours showed that the animals had no edema or erythema on the oral mucosa. CONCLUSION: The protocol changes established by the authors to prepare lyophilized bovine cancellous bone at a semi-industrial scale is reproducible and yielded a product with excellent biocompatibility.

  20. Sessions and Separability in Security Protocols

    DEFF Research Database (Denmark)

    Carbone, Marco; Guttman, Joshua

    2013-01-01

    uncompromised subset of the participants are still guar- anteed that their interaction will respect sessions. A protocol transfor- mation turns any protocol into a session-respecting protocol. We do this via a general theory of separability. Our main theorem ap- plies to different separability requirements......, and characterizes when we can separate protocol executions sufficiently to meet a particular require- ment. This theorem also gives direct proofs of some old and new protocol composition results. Thus, our theory of separability appears to cover protocol composition and session-like behavior within a uniform frame...

  1. Security Protocols: Specification, Verification, Implementation, and Composition

    DEFF Research Database (Denmark)

    Almousa, Omar

    An important aspect of Internet security is the security of cryptographic protocols that it deploys. We need to make sure that such protocols achieve their goals, whether in isolation or in composition, i.e., security protocols must not suffer from any aw that enables hostile intruders to break...... called SPS (Security Protocol Specification) language, that enables users, without requiring deep expertise in formal models from them, to specify a wide range of real-world protocols in a simple and intuitive way. Thus, SPS allows users to verify their protocols using different tools, and generate...

  2. Improvement In MAODV Protocol Using Location Based Routing Protocol

    Directory of Open Access Journals (Sweden)

    Kaur Sharnjeet

    2016-01-01

    Full Text Available Energy saving is difficult in wireless sensor network (WSN due to limited resources. Each node in WSN is constrained by their limited battery power for their energy. The energy is reduced as the time goes off due to the packet transmission and reception. Energy management techniques are necessary to minimize the total power consumption of all the nodes in the network in order to maximize its life span. Our proposed protocol Location based routing (LBR aimed to find a path which utilizes the minimum energy to transmit the packets between the source and the destination. The required energy for the transmission and reception of data is evaluated in MATLAB. LBR is implemented on Multicast Ad hoc On Demand Distance Vector Routing Protocol (MAODV to manage the energy consumption in the transmission and reception of data. Simulation results of LBR show the energy consumption has been reduced.

  3. Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design, characterization and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta; Ravani, Laura [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [BIMF/Soft Matter Electron Microscopy, University of Bayreuth (Germany); Mariani, Paolo [Department of Life and Environmental Sciences and CNISM, Università Politecnica delle Marche, I-60100 Ancona (Italy); Contado, Catia [Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ruokolainen, Janne [Department of Applied Physics, Aalto University, 00076 Aalto (Finland); Ratano, Patrizia; Campolongo, Patrizia [Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Roma (Italy); Trezza, Viviana [Department of Science, Roma Tre University, 00146 Roma (Italy); Nastruzzi, Claudio, E-mail: nas@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Cortesi, Rita [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy)

    2015-03-01

    This study describes the preparation, characterization, and in vivo evaluation in rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as prototypical cannabinoid antagonist. A study was conducted in order to optimize NLC production by melt and ultrasonication method. NLCs were prepared by alternatively adding the lipid phase into the aqueous one (direct protocol) or the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray, photon correlation spectroscopy (PCS) and sedimentation field flow fractionation (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have been determined in vitro by dialysis method. In vivo RMN biodistribution in rats was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The reverse protocol enabled to prevent the lost of lipid phase and to achieve higher RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w versus 67% w/w). The use of different protocols did not affect NLC morphology and dimensional distribution. An in vitro dissolutive release rate of RMN was calculated. The in vivo data indicate that i.n. administration of RMN by reverse NLC treated with polysorbate 80 increased RMN concentration in the brain with respect to the drug in solution. The nanoencapsulation protocol presented here appears as an optimal strategy to improve the low solubility of cannabinoid compounds in an aqueous system suitable for in vivo administration. - Highlights: • Rimonabant (RMN) can be encapsulated in nanostructured lipid carriers (NLCs). • Nanoencapsulation improves RMN solubility in a stable physiologic aqueous formulation. • RMN is released in vitro from NLC by a controlled dissolutive release modality. • I.n. administration leads to higher RMN concentration in the brain with respect to plasma. • NLC increases RMN concentration in the brain with respect to

  4. Protocols for Robust Herbicide Resistance Testing in Different Weed Species.

    Science.gov (United States)

    Panozzo, Silvia; Scarabel, Laura; Collavo, Alberto; Sattin, Maurizio

    2015-07-02

    Robust protocols to test putative herbicide resistant weed populations at whole plant level are essential to confirm the resistance status. The presented protocols, based on whole-plant bioassays performed in a greenhouse, can be readily adapted to a wide range of weed species and herbicides through appropriate variants. Seed samples from plants that survived a field herbicide treatment are collected and stored dry at low temperature until used. Germination methods differ according to weed species and seed dormancy type. Seedlings at similar growth stage are transplanted and maintained in the greenhouse under appropriate conditions until plants have reached the right growth stage for herbicide treatment. Accuracy is required to prepare the herbicide solution to avoid unverifiable mistakes. Other critical steps such as the application volume and spray speed are also evaluated. The advantages of this protocol, compared to others based on whole plant bioassays using one herbicide dose, are related to the higher reliability and the possibility of inferring the resistance level. Quicker and less expensive in vivo or in vitro diagnostic screening tests have been proposed (Petri dish bioassays, spectrophotometric tests), but they provide only qualitative information and their widespread use is hindered by the laborious set-up that some species may require. For routine resistance testing, the proposed whole plant bioassay can be applied at only one herbicide dose, so reducing the costs.

  5. The Rockefeller University Navigation Program: a structured multidisciplinary protocol development and educational program to advance translational research.

    Science.gov (United States)

    Brassil, Donna; Kost, Rhonda G; Dowd, Kathleen A; Hurley, Arlene M; Rainer, Tyler-Lauren; Coller, Barry S

    2014-02-01

    The development of translational clinical research protocols is complex. To assist investigators, we developed a structured supportive guidance process (Navigation) to expedite protocol development to the standards of good clinical practice (GCP), focusing on research ethics and integrity. Navigation consists of experienced research coordinators leading investigators through a concerted multistep protocol development process from concept initiation to submission of the final protocol. To assess the effectiveness of Navigation, we collect data on the experience of investigators, the intensity of support required for protocol development, IRB review outcomes, and protocol start and completion dates. One hundred forty-four protocols underwent Navigation and achieved IRB approval since the program began in 2007, including 37 led by trainee investigators, 26 led by MDs, 9 by MD/PhDs, 57 by PhDs, and 12 by investigators with other credentials (e.g., RN, MPH). In every year, more than 50% of Navigated protocols were approved by the IRB within 30 days. For trainees who had more than one protocol navigated, the intensity of Navigation support required decreased over time. Navigation can increase access to translational studies for basic scientists, facilitate GCP training for investigators, and accelerate development and approval of protocols of high ethical and scientific quality. © 2014 Wiley Periodicals, Inc.

  6. Suggested physical therapy protocol for reduction of lipomatosis ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the efficacy of suggested physical therapy protocol in lipomatosis dolorosa of the legs. Twenty female patients with stage I lipomatosis dolorosa of the legs ranged in age from 30 to 45 years. They received a complete decongestive physical therapy program and diet regimen.

  7. A joint research protocol for music therapy in dementia care

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner; Stige, Brynjulf

    2011-01-01

    Agitation is a major challenge within institutions of care for the elderly. The effect of music therapy on agitation and quality of live is investigated in a practice-relevant research combined with a Randomized Controlled Trial and multicentre research. The research protocol is developed...... in dialogue with practicing music therapists....

  8. Protocol and networking design issues for local access WDM networks

    NARCIS (Netherlands)

    Salvador, M.R.; Heemstra de Groot, S.M.; Niemegeers, I.G.M.M.

    This report gives an overview of some of the protocol and networking design issues that have been addressed in Flamingo, a major ongoing project which investigates the use of WDM optical technology in local access networks. Quality of service delivery and wavelength assignment are focused on in this

  9. Factors affecting SPF in vitro measurement and correlation with in vivo results.

    Science.gov (United States)

    Dimitrovska Cvetkovska, A; Manfredini, S; Ziosi, P; Molesini, S; Dissette, V; Magri, I; Scapoli, C; Carrieri, A; Durini, E; Vertuani, S

    2017-06-01

    The in vitro evaluation of SPF is still a problem due to the lack of repeatability and correlation between the in vitro and in vivo data, and many authors are currently working to develop an internationally harmonized method. Very recently, the use of several "adjuvant" ingredients such as boosters, antioxidants, immunomodulators, solvents and film-forming ingredients have further complicated the pattern for product developers that should frequently run in vivo test. The aim of this study was to understand whether a simple and cheap in vitro method could be optimized in order to provide both statistically repeatable and predictive SPF measurement. In vitro SPF assessments were carried out on 75 commercial products. The SPF was measured according to two laboratory methods (A and B), using different substrates (PMMA and surgical tape Transpore™), quantity of product and spectrophotometers. In order to evaluate whether a standard technique of spreading could lead to a statistically reliable result, we applied different spreading pressure (100 g and 200 g). Furthermore, we investigate whether other parameters characterizing the product (SPF category, filter and texture) might represent statically significant variables affecting the measures. We then compared the results obtained from in vitro SPF measure of 11 products to in vivo SPF, in order to assess the predictability of in vitro methods. Several problems were encountered in confirming the weakness of the in vitro procedures. Pressure, SPF category, filter and texture did not affect significantly the results. Overall best results were obtained with the B2 method that in terms of repeatability and predictivity provided statistically better results. Method A with Transpore™ tape showed better in vitro-in vivo correlation than Method B with PMMA plates. In our investigation, we demonstrated that it is possible for a single laboratory to optimize internal methods and protocols to achieve repeatable and predictive

  10. CArbon dioxide surgical field flooding and aortic NO-touch off-pump coronary artery bypass grafting to reduce Neurological injuries after surgical coronary revascularisation (CANON): protocol for a randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms.

    Science.gov (United States)

    Krzysztof, Szwed; Wojciech, Pawliszak; Zbigniew, Serafin; Mariusz, Kowalewski; Remigiusz, Tomczyk; Damian, Perlinski; Magdalena, Szwed; Marta, Tomaszewska; Lech, Anisimowicz; Alina, Borkowska

    2017-07-10

    Neurological injuries remain a major concern following coronary artery bypass grafting (CABG) that offsets survival benefit of CABG over percutaneous coronary interventions. Among numerous efforts to combat this issue is the development of off-pump CABG (OPCABG) that obviates the need for extracorporeal circulation and is associated with improved neurological outcomes. The objective of this study is to examine whether the neuroprotective effect of OPCABG can be further pronounced by the use of two state-of-the-art operating techniques. In this randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms, a total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio to two treatment arms and one control arm. Treatment arms undergoing either aortic no-touch OPCABG or OPCABG with partial clamp applying carbon dioxide surgical field flooding will be compared against control arm undergoing OPCABG with partial clamp. The primary endpoint will be the appearance of new lesions on control brain MRI 3 days after surgery. Secondary endpoints will include the prevalence of new focal neurological deficits in the first 7 days after surgery, the occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery and the incidence of delirium in the first 7 days after surgery. Data will be analysed on intention-to-treat principles and a per protocol basis. Ethical approval has been granted for this study. Results will be disseminated through peer-reviewed media. NCT03074604; Pre-results. 10-Mar-2017 Original. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Preliminary Investigation on In Vivo Trypanocidal Activity of ...

    African Journals Online (AJOL)

    Effect of extracts of Calotropis procera and Parkinsonia aculeata in the treatment of Trypanosoma brucei brucei infected rats was studied. The albino rats were treated for 7 days with 200mg of the plant extracts intraperitoneally (ip) after establishment of parasitaemia. No significant (p>0.05) changes in weights were ...

  12. The reliable multicast protocol application programming interface

    Science.gov (United States)

    Montgomery , Todd; Whetten, Brian

    1995-01-01

    The Application Programming Interface for the Berkeley/WVU implementation of the Reliable Multicast Protocol is described. This transport layer protocol is implemented as a user library that applications and software buses link against.

  13. Language, Semantics, and Methods for Security Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico

    are determined once and for all. The net semantics allows the derivation of general properties and proof principles the use of which is demonstrated in establishing security properties for a number of protocols. The NSL public-key protocol, the ISO 5-pass authentication and the key-translation protocols......Security protocols help in establishing secure channels between communicating systems. Great care needs therefore to be taken in developing and implementing robust protocols. The complexity of security-protocol interactions can hide, however, security weaknesses that only a formal analysis can...... reveal. The last few years have seen the emergence of successful intensional, event-based, formal approaches to reasoning about security protocols. The methods are concerned with reasoning about the events that a security protocol can perform, and make use of a causal dependency that exists between...

  14. A Wiki Based CT Protocol Management System.

    Science.gov (United States)

    Szczykutowicz, Timothy P; Rubert, Nicholas; Belden, Daryn; Ciano, Amanda; Duplissis, Andrew; Hermanns, Ashley; Monette, Stephen; Saldivar, Elliott Janssen

    2015-01-01

    At the University of Wisconsin Madison Department of Radiology, CT protocol management requires maintenance of thousands of parameters for each scanner. Managing CT protocols is further complicated by the unique configurability of each scanner. Due to recent Joint Commission requirements, now all CT protocol changes must be documented and reviewed by a site's CT protocol optimization team. The difficulty of managing the CT protocols was not in assembling the protocols, but in managing and implementing changes. This is why a wiki based solution for protocol management was implemented. A wiki inherently keeps track of all changes, logging who made the changes and when, allowing for editing and viewing permissions to be controlled, as well as allowing protocol changes to be instantly relayed to all scanner locations.

  15. In vivo gluten challenge in coeliac disease

    Directory of Open Access Journals (Sweden)

    HJ Ellis

    2001-01-01

    Full Text Available In vivo gluten challenge has been used since the early 1950s to study the role of cereal fractions in celiac disease. While early studies relied on crude indicators of celiac toxicity, the advent of jejunal biopsy and sophisticated immunohistochemical techniques has allowed accurate studies to be performed. Studies to determine the nature of the cereal component that is toxic to patients with celiac disease have concentrated on wheat because of its nutritional importance. A number of in vitro studies indicated the presence of one or more celiac-activating epitopes with the N-terminus of the A-gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acids 31 to 49 of A-gliadin. In vivo gluten challenge is the gold standard for the assessment of celiac toxicity; however, jejunal biopsy is a relatively invasive procedure, thus, other methods have been investigated. Direct infusion of the rectum with gluten has been shown to result in an increase in mucosal intraepithelial lymphocytes, occurring only in celiac patients. This method has been used to study the celiac toxicity of gliadin subfractions. The in vitro technique of small intestinal biopsy organ culture is also a useful tool and appears to give the same results as in vivo challenge. The importance of tiny amounts of gliadin in the diet, such as that which occurs in wheat starch, has been studied by in vivo challenge; this technique has clarified the position of oats in the gluten-free diet. Several studies suggest that this cereal may be included in the diet of most adult celiac patients. Studies of the transport of gliadin across the enterocyte following ingestion or challenge suggest that gliadin may be metabolized by a different pathway in celiac disease. This could result in an abnormal presentation to the immune system, triggering a pathogenic rather than a tolerogenic response.

  16. A Secure Simplification of the PKMv2 Protocol in IEEE 802.16e-2005

    DEFF Research Database (Denmark)

    Yuksel, Ender; Nielson, Hanne Riis; Nielsen, Christoffer Rosenkilde

    2007-01-01

    Static analysis is successfully used for automatically validating security properties of classical cryptographic protocols. In this paper, we shall employ the same technique to a modern security protocol for wireless networks, namely the latest version of the Privacy and Key Management protocol...... for IEEE 802.16e, PKMv2. This protocol seems to have an exaggerated mixture of security features. Thus, we iteratively investigate which components are necessary for upholding the security properties and which can be omitted safely. This approach is based on the LySa process calculus and employs...

  17. Kioto protocol; Protocolo de Kioto

    Energy Technology Data Exchange (ETDEWEB)

    Romero, A.

    2005-07-01

    Atmospheric contamination by greenhouse gases is a global problem, and thus its solution requires global measures. Although the consequences of climate change are questioned and the foreseeable effects are not excessively serious, there are plenty of scientific reasons for all countries to make the necessary efforts to meet the objectives established by the Kyoto Protocol of reducing the six greenhouse gases over the period 2008-2012. Therefore, it seems essential that we understand the nature of the transformation that are occurring in the different systems, what changes they are causing and what costs they incur. Independently of its effectiveness and realism, the Kyoto Protocol is the first regulatory step in the direction of globalization in the environmental field. (Author)

  18. Secure Multi-Player Protocols

    DEFF Research Database (Denmark)

    Fehr, Serge

    , we consider commitment multiplication proofs, which allow to prove a multiplicative relation among three commitments, and which play a crucial role in computationally secure MPC. We study a non-interactive solution which works in a distributed-verifier setting and essentially consists of a few...... executions of Pedersen’s VSS. We simplify and improve the protocol, and we point out a (previously overlooked) property which helps to construct non-interactive proofs of partial knowledge in this setting. This allows for instance to prove the knowledge of l out of m given secrets, without revealing which......While classically cryptography is concerned with the problem of private communication among two entities, say players, in modern cryptography multi-player protocols play an important role. And among these, it is probably fair to say that secret sharing, and its stronger version verifiable secret...

  19. A Model-Based Approach to Optimizing Ultradian Forced Desynchrony Protocols for Human Circadian Research.

    Science.gov (United States)

    Stack, Nora; Barker, David; Carskadon, Mary; Diniz Behn, Cecilia

    2017-10-01

    The human circadian system regulates internal 24-h rhythmicity and plays an important role in many aspects of human health and behavior. To investigate properties of the human circadian pacemaker such as intrinsic period and light sensitivity, experimental researchers have developed forced desynchrony (FD) protocols in which manipulations of the light-dark (LD) cycle are used to desynchronize the intrinsic circadian rhythm from the rest-activity cycle. FD protocols have typically been based on exposure to long LD cycles, but recently, ultradian FD protocols with short LD cycles have been proposed as a new methodology for assessing intrinsic circadian period. However, the effects of ultradian FD protocol design, including light intensity or study duration, on estimates of intrinsic circadian period have not, to our knowledge, been systematically studied. To address this gap, we applied a light-sensitive, dynamic mathematical model of the human circadian pacemaker to simulate ultradian FD protocols and analyze the effects of protocol design on estimates of intrinsic circadian period. We found that optimal estimates were obtained using protocols with low light intensities, at least 10 d of exposure to ultradian cycling, and a 7-h LD cycle duration that facilitated uniform light exposure across all circadian phases. Our results establish a theoretical framework for ultradian FD protocols that can be used to provide insights into data obtained under existing protocols and to optimize protocols for future experiments.

  20. Validity and Reproducibility of a New Treadmill Protocol: The Fitkids Treadmill Test

    NARCIS (Netherlands)

    Elle M.W. Kotte; Tim Takken; Bart C. Bongers; Janke de Groot; Alexander M.F. Winkler

    2015-01-01

    Validity and Reproducibility of a New Treadmill Protocol: The Fitkids Treadmill Test. Med. Sci. Sports Exerc., Vol. 47, No. 10, pp. 2241–2247, 2015. Purpose: This study aimed to investigate the validity and reproducibility of a new treadmill protocol in healthy children and adolescents: the Fitkids

  1. Improvement of parameters of freezing medium and freezing protocol for bull sperm using two osmotic supports.

    NARCIS (Netherlands)

    Chaveiro, A.; Machado, A.L.; Frijters, A.; Engel, B.; Woelders, H.

    2006-01-01

    The aim of this study was to improve the freezing protocol of bull sperm, by investigating the influence on sperm viability after freeze/thawing of different freezing medium components, as well as the effect of cooling rates in the different stages of the cooling protocol, in single factor

  2. Development and Pilot Study of a Welfare Assessment Protocol for Dairy Calves

    NARCIS (Netherlands)

    Barry, John Patrick; Kennedy, E.; Boer, de I.J.M.; Bokkers, E.A.M.

    2017-01-01

    As agricultural systems continue to develop and become more refined, so too must protocols used to assess the welfare of animals experiencing them. The aim of this research was to develop a welfare assessment protocol for pre-weaned dairy calves (<12 weeks old),and investigate, and improve, its

  3. The information cost of quantum memoryless protocols

    OpenAIRE

    Chailloux, André; Kerenidis, Iordanis; Laurière, Mathieu

    2017-01-01

    We consider memoryless quantum communication protocols, where the two parties do not possess any memory besides their classical input and they take turns performing unitary operations on a pure quantum state that they exchange between them. Most known quantum protocols are of this type and recently a deep connection between memoryless protocols and Bell inequality violations has been explored recently by Buhrman et al. We study the information cost of memoryless quantum protocols by looking a...

  4. Distance hijacking attacks on distance bounding protocols

    OpenAIRE

    Cremers, Cas; Rasmussen, Kasper Bonne; Čapkun, Srdjan

    2011-01-01

    Distance bounding protocols are typically analyzed with respect to three types of attacks: Distance Fraud, Mafia Fraud, and Terrorist Fraud. We define a fourth main type of attacks on distance bounding protocols, called Distance Hijacking attacks. We show that many proposed distance bounding protocols are vulnerable to these attacks, and we propose solutions to make these protocols resilient to Distance Hijacking. Additionally, we generalize Distance Hijacking to Location Hijacking, to which ...

  5. Heuristic Methods for Security Protocols

    Directory of Open Access Journals (Sweden)

    Qurat ul Ain Nizamani

    2009-10-01

    Full Text Available Model checking is an automatic verification technique to verify hardware and software systems. However it suffers from state-space explosion problem. In this paper we address this problem in the context of cryptographic protocols by proposing a security property-dependent heuristic. The heuristic weights the state space by exploiting the security formulae; the weights may then be used to explore the state space when searching for attacks.

  6. Petri Nets in Cryptographic Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Winskel, Glynn

    2001-01-01

    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate...... how the Petri-net semantics can be used to prove security properties....

  7. Building America House Simulation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Hendron, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Engebrecht, Cheryn [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2010-09-01

    The House Simulation Protocol document was developed to track and manage progress toward Building America's multi-year, average whole-building energy reduction research goals for new construction and existing homes, using a consistent analytical reference point. This report summarizes the guidelines for developing and reporting these analytical results in a consistent and meaningful manner for all home energy uses using standard operating conditions.

  8. Can in vitro mammalian cell genotoxicity test results be used to complement positive results in the Ames test and help predict carcinogenic or in vivo genotoxic activity? I. Reports of individual databases presented at an EURL ECVAM Workshop.

    Science.gov (United States)

    Kirkland, David; Zeiger, Errol; Madia, Federica; Gooderham, Nigel; Kasper, Peter; Lynch, Anthony; Morita, Takeshi; Ouedraogo, Gladys; Parra Morte, Juan Manuel; Pfuhler, Stefan; Rogiers, Vera; Schulz, Markus; Thybaud, Veronique; van Benthem, Jan; Vanparys, Philippe; Worth, Andrew; Corvi, Raffaella

    2014-12-01

    Positive results in the Ames test correlate well with carcinogenic potential in rodents. This correlation is not perfect because mutations are only one of many stages in tumour development. Also, situations can be envisaged where the mutagenic response may be specific to the bacteria or the test protocol, e.g., bacterial-specific metabolism, exceeding a detoxification threshold, or the induction of oxidative damage to which bacteria may be more sensitive than mammalian cells in vitro or tissues in vivo. Since most chemicals are also tested for genotoxicity in mammalian cells, the pattern of mammalian cell results may help identify whether Ames-positive results predict carcinogenic or in vivo mutagenic activity. A workshop was therefore organised and sponsored by the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) to investigate this further. Participants presented results from other genotoxicity tests with Ames-positive compounds. Data came from published, regulatory agency, and industry sources. The question was posed whether negative results in mammalian cell tests were associated with absence of carcinogenic or in vivo genotoxic activity despite a positive Ames test. In the limited time available, the presented data were combined and an initial analysis suggested that the association of negative in vitro mammalian cell test results with lack of in vivo genotoxic or carcinogenic activity could have some significance. Possible reasons why a positive Ames test may not be associated with in vivo activity and what additional investigations/tests might contribute to a more robust evaluation were discussed. Because a considerable overlap was identified among the different databases presented, it was recommended that a consolidated database be built, with overlapping chemicals removed, so that a more robust analysis of the predictive capacity for potential carcinogenic and in vivo genotoxic activity could be derived from the patterns of mammalian

  9. Near-infrared molecular probes for in vivo imaging.

    Science.gov (United States)

    Zhang, Xuan; Bloch, Sharon; Akers, Walter; Achilefu, Samuel

    2012-04-01

    Cellular and tissue imaging in the near-infrared (NIR) wavelengths between 700 and 900 nm is advantageous for in vivo imaging because of the low absorption of biological molecules in this region. This unit presents protocols for small animal imaging using planar and fluorescence lifetime imaging techniques. Included is an overview of NIR fluorescence imaging of cells and small animals using NIR organic fluorophores, nanoparticles, and multimodal imaging probes. The development, advantages, and application of NIR fluorescent probes that have been used for in vivo imaging are also summarized. The use of NIR agents in conjunction with visible dyes and considerations in selecting imaging agents are discussed. We conclude with practical considerations for the use of these dyes in cell and small animal imaging applications.

  10. Umsetzung des KDSF-Datenmodells in VIVO

    OpenAIRE

    Walther, Tatiana; Hauschke, Christian

    2017-01-01

    Im Rahmen des Projekts „Umsetzung Kerndatensatz Forschung in VIVO“ wird am Open Science Lab der Technischen Informationsbibliothek Hannover (TIB) der Versuch unternommen, den Kerndatensatz Forschung in das Forschungsinformationssystem VIVO zu integrieren. Entwurf KDSF-VIVO-Alignment und KDSF-VIVO-Extension: https://github.com/VIVO-DE/VIVO-KDSF-Integration

  11. Advanced dementia pain management protocols.

    Science.gov (United States)

    Montoro-Lorite, Mercedes; Canalias-Reverter, Montserrat

    2017-08-04

    Pain management in advanced dementia is complex because of neurological deficits present in these patients, and nurses are directly responsible for providing interventions for the evaluation, management and relief of pain for people suffering from this health problem. In order to facilitate and help decision-makers, pain experts recommend the use of standardized protocols to guide pain management, but in Spain, comprehensive pain management protocols have not yet been developed for advanced dementia. This article reflects the need for an integrated management of pain in advanced dementia. From the review and analysis of the most current and relevant studies in the literature, we performed an approximation of the scales for the determination of pain in these patients, with the observational scale PAINAD being the most recommended for the hospital setting. In addition, we provide an overview for comprehensive management of pain in advanced dementia through the conceptual framework «a hierarchy of pain assessment techniques by McCaffery and Pasero» for the development and implementation of standardized protocols, including a four-phase cyclical process (evaluation, planning/performance, revaluation and recording), which can facilitate the correct management of pain in these patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  12. IPv6: The Next Generation Internet Protocol

    Indian Academy of Sciences (India)

    internet. 2. New Features in IPv6. Harsha Srinath. IPv4, the workhorse protocol of the currently popular TePI. IP protocol suite, is fast becoming obsolete. The exponen- ... required the creation of the next generation of Internet. Protocol-IPv6. ..... using multiple access providers across the same interface to have separate ...

  13. Tool Supported Analysis of Web Services Protocols

    DEFF Research Database (Denmark)

    Marques, Abinoam P.; Ravn, Anders Peter; Srba, Jiri

    2011-01-01

    to ensure the finiteness of the protocol state-spaces while still being able to verify interesting protocol properties. The translations for different kinds of communication media have been implemented and successfully tested, among others, on agreement protocols from WS-Business Activity....

  14. IPv6: The Next Generation Internet Protocol

    Indian Academy of Sciences (India)

    IPv4, the workhorse protocol of the currently popular TePI. IP protocol suite, is fast becoming obsolete. The exponen- tial growth of the Internet is the main reason that has required the creation of the next generation of Internet. Protocol- IPv6. IPv6 is much more flexible and promises to take care of the address space and ...

  15. PCR protocols: current methods and applications

    National Research Council Canada - National Science Library

    White, Bruce Alan

    1993-01-01

    ..." between "small" and "big" labs, since its use makes certain projects, especially those related to molecular cloning, now far more feasible for the small lab with a modest budget. This new volume on PCR Protocols does not attempt the impossible task of representing all PCR-based protocols. Rather, it presents a range of protocols, both analytical ...

  16. Timed Model Checking of Security Protocols

    NARCIS (Netherlands)

    Corin, R.J.; Etalle, Sandro; Hartel, Pieter H.; Mader, Angelika H.

    We propose a method for engineering security protocols that are aware of timing aspects. We study a simplified version of the well-known Needham Schroeder protocol and the complete Yahalom protocol. Timing information allows the study of different attack scenarios. We illustrate the attacks by model

  17. In vitro and in vivo production of pectic enzymes, polygalacturonase ...

    African Journals Online (AJOL)

    Possible in vitro and in vivo production of pectic enzyme polygalacturonase and pH on the activity of the enzyme were investigated. The results of the assay for the production of polygalacturonase (PG) by the pathogen showed that the activity was 142.9 RVU in vitro and 166.7 RVU, in vivo at temperature 25°C. The optimum ...

  18. Dissecting Neuronal Participation to Focal Epileptic Events in Vivo

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0631 TITLE: Dissecting Neuronal Participation to Focal Epileptic Events in Vivo PRINCIPAL INVESTIGATOR: Stelios M...SUBTITLE 5a. CONTRACT NUMBER Dissecting Neuronal Participation to Focal Epileptic Events in Vivo 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...rational approaches to therapy we need to understand the role that individual neurons of different types play in epileptic events. The two-photon

  19. Impact of Cosmetic Lotions on Nanoparticle Penetration through ex Vivo C57BL/6 Hairless Mouse and Human Skin: A Comparison Study

    Directory of Open Access Journals (Sweden)

    Samreen Jatana

    2016-02-01

    Full Text Available Understanding the interactions of nanoparticles (NPs with skin is important from a consumer and occupational health and safety perspective, as well as for the design of effective NP-based transdermal therapeutics. Despite intense efforts to elucidate the conditions that permit NP penetration, there remains a lack of translatable results from animal models to human skin. The objectives of this study are to investigate the impact of common skin lotions on NP penetration and to quantify penetration differences of quantum dot (QD NPs between freshly excised human and mouse skin. QDs were mixed in seven different vehicles, including five commercial skin lotions. These were topically applied to skin using two exposure methods; a petri dish protocol and a Franz diffusion cell protocol. QD presence in the skin was quantified using Confocal Laser Scanning Microscopy. Results show that the commercial vehicles can significantly impact QD penetration in both mouse and human skin. Lotions that contain alpha hydroxyl acids (AHA facilitated NP penetration. Lower QD signal was observed in skin studied using a Franz cell. Freshly excised human skin was also studied immediately after the sub-cutaneous fat removal process, then after 24 h rest ex vivo. Resting human skin 24 h prior to QD exposure significantly reduced epidermal presence. This study exemplifies how application vehicles, skin processing and the exposure protocol can affect QD penetration results and the conclusions that maybe drawn between skin models.

  20. Impact of Cosmetic Lotions on Nanoparticle Penetration through ex vivo C57BL/6 Hairless Mouse and Human Skin: A Comparison Study

    Science.gov (United States)

    Jatana, Samreen; Callahan, Linda M.; Pentland, Alice P.; DeLouise, Lisa A.

    2016-01-01

    Understanding the interactions of nanoparticles (NPs) with skin is important from a consumer and occupational health and safety perspective, as well as for the design of effective NP-based transdermal therapeutics. Despite intense efforts to elucidate the conditions that permit NP penetration, there remains a lack of translatable results from animal models to human skin. The objectives of this study are to investigate the impact of common skin lotions on NP penetration and to quantify penetration differences of quantum dot (QD) NPs between freshly excised human and mouse skin. QDs were mixed in 7 different vehicles, including 5 commercial skin lotions. These were topically applied to skin using two exposure methods; a petri dish protocol and a Franz diffusion cell protocol. QD presence in the skin was quantified using Confocal Laser Scanning Microscopy. Results show that the commercial vehicles can significantly impact QD penetration in both mouse and human skin. Lotions that contain alpha hydroxyl acids (AHA) facilitated NP penetration. Lower QD signal was observed in skin studied using a Franz cell. Freshly excised human skin was also studied immediately after the sub-cutaneous fat removal process, then after 24 hours rest ex vivo. Resting human skin 24 hours prior to QD exposure significantly reduced epidermal presence. This study exemplifies how application vehicles, skin processing and the exposure protocol can affect QD penetration results and the conclusions that maybe drawn between skin models. PMID:27453793

  1. Impact of Cosmetic Lotions on Nanoparticle Penetration through ex vivo C57BL/6 Hairless Mouse and Human Skin: A Comparison Study.

    Science.gov (United States)

    Jatana, Samreen; Callahan, Linda M; Pentland, Alice P; DeLouise, Lisa A

    2016-03-01

    Understanding the interactions of nanoparticles (NPs) with skin is important from a consumer and occupational health and safety perspective, as well as for the design of effective NP-based transdermal therapeutics. Despite intense efforts to elucidate the conditions that permit NP penetration, there remains a lack of translatable results from animal models to human skin. The objectives of this study are to investigate the impact of common skin lotions on NP penetration and to quantify penetration differences of quantum dot (QD) NPs between freshly excised human and mouse skin. QDs were mixed in 7 different vehicles, including 5 commercial skin lotions. These were topically applied to skin using two exposure methods; a petri dish protocol and a Franz diffusion cell protocol. QD presence in the skin was quantified using Confocal Laser Scanning Microscopy. Results show that the commercial vehicles can significantly impact QD penetration in both mouse and human skin. Lotions that contain alpha hydroxyl acids (AHA) facilitated NP penetration. Lower QD signal was observed in skin studied using a Franz cell. Freshly excised human skin was also studied immediately after the sub-cutaneous fat removal process, then after 24 hours rest ex vivo. Resting human skin 24 hours prior to QD exposure significantly reduced epidermal presence. This study exemplifies how application vehicles, skin processing and the exposure protocol can affect QD penetration results and the conclusions that maybe drawn between skin models.

  2. Detection of Oncogene-Induced Senescence In Vivo.

    Science.gov (United States)

    Baek, Kwan-Hyuck; Ryeom, Sandra

    2017-01-01

    Oncogene-induced senescence or OIS is defined as a permanent state of proliferative arrest resulting from an activating oncogenic-lesion. OIS has been suggested to function as a cancer cell intrinsic mechanism to restrain tumor growth and has been implicated as a key mechanism preventing the progression of certain premalignant lesions in genetically engineered mouse models of cancer. The senescent phenotype can be defined by two criteria that include cell cycle arrest and resistance to mitogens and oncogenic transformation. While the phenotype and properties of senescent cells in vitro are well described, the morphological characteristics defining senescence in vivo have been controversial with no specific marker that definitively proves a senescent state. Indeed, many of the published in vivo markers to identify and characterize senescence in an organism are unreliable and often times have been found to be nonspecific. However, the use of multiple markers is accepted as confirmation of senescence in vivo. Here, we describe protocols for some of the most commonly used indicators of senescence in oncogenic Kras-induced lung adenomas including the detection of senescence-associated beta-galactosidase, expression of the tumor suppressor p19 ARF , the presence of senescence-associated heterochromatin foci, and in vivo BrdU uptake to confirm cell cycle arrest.

  3. Perceptions of Pediatric Critical Care Nurses on the Initiation of a Nursing-Led Feeding Protocol.

    Science.gov (United States)

    Kirk, Angela Hui Ping; Ng, Brenda Sok Peng; Lee, Ang Noi; Ang, Bixia; Lee, Jan Hau

    2015-12-01

    Critically ill children frequently receive inadequate nutritional support. Feeding protocols have been shown to facilitate optimal nutritional care. We aim to determine the perceptions of critical care nurses with regard to the implementation of a feeding protocol as well as to their preferred teaching methods before introducing this protocol in our pediatric intensive care unit (PICU). We hypothesize that nursing experience and educational level are factors that predict readiness to adopt this protocol. All PICU nurses were invited to participate in an online survey to investigate their perceptions on protocol implementation and on preferred teaching methods. Statistical analysis was performed using simple logistic regression and the Fisher exact test. Statistical significance was taken as p nurses completed the survey. Fifty-four (73%) had nursing degrees. Mean duration of PICU experience was 6.2 years (5th, 95th percentile: 1, 15). Three quarters of participants (74%, n = 55) felt that they did not have sufficient knowledge regarding feeding protocols, and 86% (n = 64) expressed that they were keen to implement a feeding protocol. There was no association between readiness to adopt the feeding protocol with years of ICU experience (OR = 0.99, 95% CI [0.84, 1.18]) and educational level (OR = 1.43, 95% CI [0.31, 6.68]). The preferred teaching methods were bedside teaching (61%), didactic lectures (51%), and the distribution of protocol manuals (50%). PICU nurses felt that the advantages of a feeding protocol included standardization of practice, optimization of patient's nutritional intake, earlier initiation of feeding, increased patient safety, and the extension of nursing roles. Perceived disadvantages included inapplicability of the feeding protocol to all patients, lack of flexibility in feeding management, increased confusion, and doctors placing little value on the feeding protocol. This study found that nursing experience and level of education do not

  4. Wireless Power Transfer Protocols in Sensor Networks: Experiments and Simulations

    Directory of Open Access Journals (Sweden)

    Sotiris Nikoletseas

    2017-04-01

    Full Text Available Rapid technological advances in the domain of Wireless Power Transfer pave the way for novel methods for power management in systems of wireless devices, and recent research works have already started considering algorithmic solutions for tackling emerging problems. In this paper, we investigate the problem of efficient and balanced Wireless Power Transfer in Wireless Sensor Networks. We employ wireless chargers that replenish the energy of network nodes. We propose two protocols that configure the activity of the chargers. One protocol performs wireless charging focused on the charging efficiency, while the other aims at proper balance of the chargers’ residual energy. We conduct detailed experiments using real devices and we validate the experimental results via larger scale simulations. We observe that, in both the experimental evaluation and the evaluation through detailed simulations, both protocols achieve their main goals. The Charging Oriented protocol achieves good charging efficiency throughout the experiment, while the Energy Balancing protocol achieves a uniform distribution of energy within the chargers.

  5. Quantum fluctuation theorems and generalized measurements during the force protocol.

    Science.gov (United States)

    Watanabe, Gentaro; Venkatesh, B Prasanna; Talkner, Peter; Campisi, Michele; Hänggi, Peter

    2014-03-01

    Generalized measurements of an observable performed on a quantum system during a force protocol are investigated and conditions that guarantee the validity of the Jarzynski equality and the Crooks relation are formulated. In agreement with previous studies by M. Campisi, P. Talkner, and P. Hänggi [Phys. Rev. Lett. 105, 140601 (2010); Phys. Rev. E 83, 041114 (2011)], we find that these fluctuation relations are satisfied for projective measurements; however, for generalized measurements special conditions on the operators determining the measurements need to be met. For the Jarzynski equality to hold, the measurement operators of the forward protocol must be normalized in a particular way. The Crooks relation additionally entails that the backward and forward measurement operators depend on each other. Yet, quite some freedom is left as to how the two sets of operators are interrelated. This ambiguity is removed if one considers selective measurements, which are specified by a joint probability density function of work and measurement results of the considered observable. We find that the respective forward and backward joint probabilities satisfy the Crooks relation only if the measurement operators of the forward and backward protocols are the time-reversed adjoints of each other. In this case, the work probability density function conditioned on the measurement result satisfies a modified Crooks relation. The modification appears as a protocol-dependent factor that can be expressed by the information gained by the measurements during the forward and backward protocols. Finally, detailed fluctuation theorems with an arbitrary number of intervening measurements are obtained.

  6. Zebrafish embryology and cartilage staining protocols for high school students.

    Science.gov (United States)

    Emran, Farida; Brooks, Jacqueline M; Zimmerman, Steven R; Johnson, Susan L; Lue, Robert A

    2009-06-01

    The Life Sciences-Howard Hughes Medical Institute Outreach Program at Harvard University supports high school science education by offering an on-campus program for students and their teachers to participate in investigative, hands-on laboratory sessions. The outreach program has recently designed and launched a successful zebrafish embryology protocol that we present here. The main objectives of this protocol are to introduce students to zebrafish as a model research organism and to provide students with direct experience with current techniques used in embryological research. The content of the lab is designed to generate discussions on embryology, genetics, fertilization, natural selection, and animal adaptation. The protocol produces reliable results in a time-efficient manner using a minimum of reagents. The protocol presented here consists of three sections: observations of live zebrafish larvae at different developmental stages, cartilage staining of zebrafish larvae, and a mutant hunt involving identification of two zebrafish mutants (nacre and chokh). Here, we describe the protocol, show the results obtained for each section, and suggest possible alternatives for different lab settings.

  7. Data structure of search & compare (S&C) reservation protocol

    Science.gov (United States)

    Markovič, Miroslav; Dubovan, Jozef; Dado, Milan; Benedikovič, Daniel; Litvík, Ján.

    2012-01-01

    On the present time, the most used technology of core networks is Wavelength-division multiplexing (WDM) which save a lot of bandwidth of optical fiber. But in each node all optical signals must be converted into the electrical domain, processed and converted back into the optical domain. Result of all these steps is that the data spend in the node a lot of time. This time decreases total available bandwidth in the optical networks. One of the results is that we compose WDM nodes which represent hybrid system of switching and controlling. If we use out-of-band signalizing it is simpler to separate control head from the data. For effective control and transmission of data over the optical networks, the reservation protocols are needed in WDM/OBS4,5. In today's networks exist a lot of the protocols, which have their own advantages and disadvantages. For our investigation it was chosen the reservation protocol called Search & Compare (S &C)1, because it uses parallel-segment based and parallel link reservation. The structure of data will be designed from the point of view of wavelength for transmission channels, length of optical burst, source and group addresses in the segment, number of nodes and the total time needed for switching. Structure of the protocol will contain all of the control messages which are necessary for reservation a path along all segments. The design of the protocol follows the ITU-T recommendation2,3.

  8. Methods of in-vivo mouse lung micro-CT

    Science.gov (United States)

    Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric

    2005-04-01

    Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated

  9. On Protocol Security in the Cryptographic Model

    DEFF Research Database (Denmark)

    Nielsen, Jesper Buus

    the channels by which they communicate. A general solution to the secure multiparty computation problem is a compiler which given any feasible function describes an efficient protocol which allows the parties to compute the function securely on their local inputs over an open network. Over the past twenty...... previous approaches to the problem. Starting from an open point-to-point network there is a long way to general secure multiparty computation. The dissertation contains contributions at several points along the way. In particular we investigate how to realize secure channels. We also show how threshold...... you as possible. This is the general problem of secure multiparty computation. The usual way of formalizing the problem is to say that a number of parties who do not trust each other wish to compute some function of their local inputs, while keeping their inputs as secret as possible and guaranteeing...

  10. Chest magnetic resonance imaging: a protocol suggestion

    Directory of Open Access Journals (Sweden)

    Bruno Hochhegger

    2015-12-01

    Full Text Available Abstract In the recent years, with the development of ultrafast sequences, magnetic resonance imaging (MRI has been established as a valuable diagnostic modality in body imaging. Because of improvements in speed and image quality, MRI is now ready for routine clinical use also in the study of pulmonary diseases. The main advantage of MRI of