38 research outputs found

    Impact of changing computer technology on hydrologic and water resource modeling

    Get PDF
    The increasing availability of substantial computer power at relatively low costs and the increasing ease of using computer graphics, of communicating with other computers and data bases, and of programming using high-level problem-oriented computer languages, is providing new opportunities and challenges for those developing and using hydrologic and water resources models. This paper reviews some of the progress made towards the development and application of computer support systems designed to aid those involved in analyzing hydrologic data and in operating, managing, or planning water resource facilities. Such systems of hardware and software are being designed to allow direct and easy access to a broad and heterogeneous group of users. These systems often combine data-base management; simulation and optimization techniques; symbolic colored displays; heuristic, qualitative approaches; and possibly artificial intelligence methods in an interactive, user-controlled, easily accessible interface. Individuals involved in the use of such systems are not only those with technical training, but also those representing different interest groups and having non-technical backgrounds. The essential difference between what is happening now and the more traditional off-line, non-interactive approaches is that instead of generating solutions to specific problems, model developers are now beginning to deliver, in a much more useful and user-friendly form, computer-based turnkey systems for exploring, analyzing and synthesizing plans or policies. Such tools permit the user to evaluate alternative solutions based on his or her own objectives and subjective judgments in an interactive learning and decision-making process

    Effect of O-Phenoxy Caspase Inhibitors on Apoptosis

    No full text
    Apoptosis is a process of cell death, in which a cell commits suicide. Apoptosis is essential for the maintenance of homeostasis and apoptotic dysregulation has been implicated numerous human diseases. Apoptotic events are mediated through a unique family of aspartyl proteases, caspases. Our study tested the effectiveness of nontoxic, O-phenoxy-conjugates caspase inhibitors to prevent cell death. Human leukemia cells were treated with Boc-D(OMe)-OPh, Cbz-D(OMe)-OPh, Q-D(OMe)-OPh, Boc-VD(OMe)-OPh, Cbz-VD(OMe)-OPh, Q-VD(OMe)-OPh, and Q-VE(OMe)-OPh. The cells were induced to undergo apoptosis and the inhibitory effectiveness of the compounds was evaluated. Our results indicate the drugs that contained the dipeptide VD were more effective at inhibiting cell death than those that contained aspartic acid (D) alone. Q-VE(OMe)-OPh had no apoptotic inhibitory activity and was identified as the first true O-phenoxy conjugate, negative control. Our data suggest that N-terminal protecting groups and amino acid composition significantly alter the effectiveness of peptide-based cell death inhibitors

    Video-Based Facial Weakness Analysis.

    No full text
    OBJECTIVE: Facial weakness is a common sign of neurological diseases such as Bell\u27s palsy and stroke. However, recognizing facial weakness still remains as a challenge, because it requires experience and neurological training. METHODS: We propose a framework for facial weakness detection, which models the temporal dynamics of both shape and appearance-based features of each target frame through a bi-directional long short-term memory network (Bi-LSTM). The system is evaluated on a in-the-wild video dataset that is verified by three board-certified neurologists. In addition, three emergency medical services (EMS) personnel and three upper level residents rated the dataset. We compare the evaluation of the proposed algorithm with other comparison methods as well as the human raters. RESULTS: Experimental evaluation demonstrates that: (1) the proposed algorithm achieves the accuracy, sensitivity, and specificity of 94.3%, 91.4%, and 95.7%, which outperforms other comparison methods and achieves the equal performance to paramedics; (2) the framework can provide visualizable and interpretable results that increases model transparency and interpretability; (3) a prototype is implemented as a proof-of-concept showcase to show the feasibility of an inexpensive solution for facial weakness detection. CONCLUSION: The experiment results suggest that the proposed framework can identify facial weakness effectively. SIGNIFICANCE: We provide a proof-of-concept study, showing that such technology could be used by non-neurologists to more readily identify facial weakness in the field, leading to increasing coverage and earlier treatment

    Effect of O-Phenoxy Caspase Inhibitors on Apoptosis

    No full text
    Apoptosis is a process of cell death, in which a cell commits suicide. Apoptosis is essential for the maintenance of homeostasis and apoptotic dysregulation has been implicated numerous human diseases. Apoptotic events are mediated through a unique family of aspartyl proteases, caspases. Our study tested the effectiveness of nontoxic, O-phenoxy-conjugates caspase inhibitors to prevent cell death. Human leukemia cells were treated with Boc-D(OMe)-OPh, Cbz-D(OMe)-OPh, Q-D(OMe)-OPh, Boc-VD(OMe)-OPh, Cbz-VD(OMe)-OPh, Q-VD(OMe)-OPh, and Q-VE(OMe)-OPh. The cells were induced to undergo apoptosis and the inhibitory effectiveness of the compounds was evaluated. Our results indicate the drugs that contained the dipeptide VD were more effective at inhibiting cell death than those that contained aspartic acid (D) alone. Q-VE(OMe)-OPh had no apoptotic inhibitory activity and was identified as the first true O-phenoxy conjugate, negative control. Our data suggest that N-terminal protecting groups and amino acid composition significantly alter the effectiveness of peptide-based cell death inhibitors

    Q-VE-OPh, a Negative Control for O-Phenoxy-Conjugated Caspase Inhibitors

    Get PDF
    The broad-spectrum apoptosis (caspase) inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibi- tor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh, thereby retaining the identical charge and molecular properties with only the addition of an extra –CH2 group. The purity and quality were assessed by ion trap mass spectrometry and verified by nuclear magnetic resonance. We determined the effectiveness of Q-VE-OPh, in comparison to Q-VD-OPh, to prevent DNA fragmentation in human Jurkat T leukemia cells that were induced to undergo apoptosis. DNA fragmentation was analyzed by agarose gel electrophoresis for the presence of DNA laddering, the hallmark indicator of apoptosis. Our results indicate that apoptosis was potently inhibited by Q-VD-OPh. In stark contrast, Q-VE-OPh did not inhibit apoptosis at a similar dose but required at least 20 times greater concentration than Q-VD-OPh to have any inhibitory effect. Western blot analysis showed that Q-VE-OPh was similarly less effective at inhibiting the activation of the extrinsic (caspase 8) and intrinsic (caspase 9) initiator caspases. Cell proliferation and viability studies further demonstrate that Q-VE-OPh is non-toxic, even at high concentration. Our data indicate that the specificity, effectiveness, and absence of toxicity of Q-VE-OPh provides the appropriate and superior negative control for in vitro and in vivo studies when analyzing the effects of o-phenoxy caspase inhibitors
    corecore