115 research outputs found

    Minimum Energy Broadcast and Disk Cover in Grid Wireless Networks

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    Abstract. The Minimum Energy Broadcast problem consists in finding the minimum-energy range assignment for a given set S of n stations of an ad hoc wireless network that allows a source station to perform broadcast operations over S. We prove a nearly tight asymptotical bound on the optimal cost for the Minimum Energy Broadcast problem on square grids. We emphasize that finding tight bounds for this problem restriction is far to be easy: it involves the Gauss’s Circle problem and the Apollonian Circle Packing. We also derive near-tight bounds for the Bounded-Hop version of this problem. Our results imply that the best-known heuristic, the MST-based one, for the Minimum Energy Broadcast problem is far to achieve optimal solutions (even) on very regular, well-spread instances: its worst-case approximation ratio is about pi and it yields Ω( n) hops. As a by product, we get nearly tight bounds for the Minimum Disk Cover problem and for its restriction in which the allowed disks must have non-constant radius. Finally, we emphasize that our upper bounds are obtained via polynomial time constructions.

    Avaliação da Vergonha em Adolescentes: ‘The Other as Shamer Scale’

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    Shame, as a self-conscious, multidimensional and socially focused emotion, plays a central role in the mental health of individuals. In adolescents, shame is also a frequent experience and its assessment is important for research and clinical practice. This study aims to validate a brief measure of external shame (Other as Shamer Scale – brief version for adolescents: (OASB-A). The participants were 834 adolescents with a mean age of 15 years. The final model of the OASB-A (8 items), obtained through CFA, presents a good fit to the data. The OASB-A shows a good internal consistency and an adequate temporal reliability. The OASB-A also reveals significant correlations with traumatic shame experiences (IES-R) and psychopathological symptoms (DASS-21). The OASB-A is an economic and reliable measure to assess external shame in adolescents

    A Pan-GTPase inhibitor as a molecular probe

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    Overactive GTPases have often been linked to human diseases. The available inhibitors are limited and have not progressed far in clinical trials. We report here a first-in-class small molecule pan-GTPase inhibitor discovered from a high throughput screening campaign. The compound CID1067700 inhibits multiple GTPases in biochemical, cellular protein and protein interaction, as well as cellular functional assays. In the biochemical and protein interaction assays, representative GTPases from Rho, Ras, and Rab, the three most generic subfamilies of the GTPases, were probed, while in the functional assays, physiological processes regulated by each of the three subfamilies of the GTPases were examined. The chemical functionalities essential for the activity of the compound were identified through structural derivatization. The compound is validated as a useful molecular probe upon which GTPase-targeting inhibitors with drug potentials might be developed

    A selective ATP-binding cassette subfamily G member 2 efflux inhibitor revealed via high-throughput flow cytometry

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    Chemotherapeutics tumor resistance is a principal reason for treatment failure, and clinical and experimental data indicate that multidrug transporters such as ATP-binding cassette (ABC) B1 and ABCG2 play a leading role by preventing cytotoxic intracellular drug concentrations. Functional efflux inhibition of existing chemotherapeutics by these pumps continues to present a promising approach for treatment. A contributing factor to the failure of existing inhibitors in clinical applications is limited understanding of specific substrate/inhibitor/pump interactions. We have identified selective efflux inhibitors by profiling multiple ABC transporters against a library of small molecules to find molecular probes to further explore such interactions. In our primary screening protocol using JC-1 as a dual-pump fluorescent reporter substrate, we identified a piperazine-substituted pyrazolo[1,5-a]pyrimidine substructure with promise for selective efflux inhibition. As a result of a focused structure-activity relationship (SAR)-driven chemistry effort, we describe compound 1 (CID44640177), an efflux inhibitor with selectivity toward ABCG2 over ABCB1. Compound 1 is also shown to potentiate the activity of mitoxantrone in vitro as well as preliminarily in vivo in an ABCG2-overexpressing tumor model. At least two analogues significantly reduce tumor size in combination with the chemotherapeutic topotecan. To our knowledge, low nanomolar chemoreversal activity coupled with direct evidence of efflux inhibition for ABCG2 is unprecedented
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