45 research outputs found

    Interactive Information System for Technology Assessments

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    Evaluation and assessment of new technologies is a rather complicated task due to the involvement of groups of experts, multiple criteria characterizing several alternatives as well as incomplete information about these alternatives. Expert analysis of new technologies by different aspects can be one of the ways of estimating the advantages and shortcomings of each of them and of forecasting their development and usage. Due to the character of the assessment procedure, especially in the group expert situation, large amounts of information must be processed and analyzed in order to find the final conclusion. Additionally, several factors reflecting the quality of the results, quality of experts opinions, etc. must be calculated during the assessment process. Therefore, this task should be supported by some computer based tools. The paper presents such an information management system supporting the process of technology assessment. The system performs such functions like information collection and storage, interaction with experts and analysts, aggregation of information, graphic presentation of data and results as well as computes several statistical factors necessary to analyze the data submitted by experts. The system, being the first step towards development of more advanced decision support systems has been applied at IIASA for analysis of several technologies for energy production

    Non-NAD-Like poly(ADP-Ribose) Polymerase-1 Inhibitors effectively Eliminate Cancer in vivo

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    The clinical potential of PARP-1 inhibitors has been recognized N10 years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problemfor their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors. The majority of PARP-1 inhibitors known to date have been developed as NAD competitors. NAD is utilized by many enzymes other than PARP-1, resulting in a trade-off trap between their specificity and efficacy. To circumvent this problem, we have developed a new strategy to blindly screen a small molecule library for PARP-1 inhibitors by targeting a highly specific rout of its activation. Based on this screen, we present a collection of PARP-1 inhibitors and provide their structural classification. In addition to compounds that show structural similarity to NAD or known PARP-1 inhibitors, the screen identified structurally newnon-NAD-like inhibitors that block PARP-1 activity in cancer cellswith greater efficacy and potency than classical PARP-1 inhibitors currently used in clinic. These non-NAD-like PARP-1 inhibitors are effective against several types of human cancer xenografts, including kidney, prostate, and breast tumors in vivo. Our pre-clinical testing of these inhibitors using laboratory animals has established a strong foundation for advancing the new inhibitors to clinical trials

    A Four-Gap Glass-RPC Time-of-Flight Array with 90 ps Time Resolution

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    In this paper, we describe the performance of a prototype developed in the context of the ALICE time-of-flight research and development system. The detector module consists of a 32-channel array of 3 x 3 cm2 glass resistive plate chamber (RPC) cells, each of which has four accurately space gaps of 0.3 mm thickness arranged as a pair of double-gap resisitive plate chambers. Operated with a nonflammable gas mixture at atmospheric pressure, the system achieved a time resolution of 90 ps at 98% efficiency with good uniformity and moderate crosstalk. This result shows the feasibility of large-area high-resolution time-of-flight systems based on RPCs at affordable cost

    Non-NAD-Like poly(ADP-Ribose) Polymerase-1 Inhibitors effectively Eliminate Cancer in vivo

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    The clinical potential of PARP-1 inhibitors has been recognized >10 years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problem for their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors. The majority of PARP-1 inhibitors known to date have been developed as NAD competitors. NAD is utilized by many enzymes other than PARP-1, resulting in a trade-off trap between their specificity and efficacy. To circumvent this problem, we have developed a new strategy to blindly screen a small molecule library for PARP-1 inhibitors by targeting a highly specific rout of its activation. Based on this screen, we present a collection of PARP-1 inhibitors and provide their structural classification. In addition to compounds that show structural similarity to NAD or known PARP-1 inhibitors, the screen identified structurally new non-NAD-like inhibitors that block PARP-1 activity in cancer cells with greater efficacy and potency than classical PARP-1 inhibitors currently used in clinic. These non-NAD-like PARP-1 inhibitors are effective against several types of human cancer xenografts, including kidney, prostate, and breast tumors in vivo. Our pre-clinical testing of these inhibitors using laboratory animals has established a strong foundation for advancing the new inhibitors to clinical trials

    Goldenhar syndrome: a cause of secondary immunodeficiency?

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    <p>Abstract</p> <p>Goldenhar syndrome (GS) results from an aberrant development of the 1<sup>st</sup> and 2<sup>nd</sup> branchial arches. There is a wide range of clinical manifestations, the most common being microtia, hemifacial microsomia, epibulbar dermoids and vertebral malformations. We present two cases of GS and secondary immunodeficiency due to anatomical defects characteristic of this disorder. Case 1 (3-year-old female) averaged 6 episodes of sinusitis and otitis media per year. Case 2 (7-year-old female) also had recurrent otitis media, an episode of bacterial pneumonia, and 2 episodes of bacterial meningitis. Their immune evaluation included a complete blood count with differential, serum immunoglobulin levels and specific antibody concentrations, lymphocyte phenotyping, and mitogen and antigen responses, the results of which were all within normal ranges. Both children demonstrated major structural abnormalities of the inner and middle ear structures, retention of fluid in mastoid air cells, and chronic sinusitis by computed tomography. These two cases illustrate how a genetically-associated deviation of the middle ear cleft can cause recurrent infections and chronic inflammation of the middle ear and adjacent sinuses, even meninges, leading to a greatly reduced quality of life for the child and parents.</p
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