10 research outputs found

    Does death penalty have a deterrent effect on homicides?

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    Death penalty has been practiced by most societies in the past but a growing number of countries have abolished this sanction. Among all debates about whether to retain or abolish death penalty, the effect of death penalty on deterring homicides is the most controversial arguing point. This paper aims at examining the significance of deterrent effects of death penalty, taking into consideration country-specific economic climates, in order to provide policy makers with meaningful insights so as to make better-informed decisions. In this paper, we employ detailed information of death penalty and its executions in 50 U.S. states and 49 other countries in years 1995-2012 to conduct OLS and 2SLS regression analysis. Besides, we also explore whether the strength of the deterrent effect varies with economic factors, through adding in interaction of death penalty with GDP per capita and unemployment rate and subsequently suitable groupings. The results of OLS panel data and 2SLS regression consistently return insignificant deterrent effect of death penalty on homicide rates. Further investigations reveal that death penalty is more effective in deterring homicides in countries with poor economic conditions, indicated by lower per capita GDP and higher unemployment rate.Bachelor of Art

    Radial Size of a Starburst Dendrimer in Solvents of Varying Quality

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    Active Learning with Query Generation for Cost-Effective Text Classification

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    Labeling a text document is usually time consuming because it requires the annotator to read the whole document and check its relevance with each possible class label. It thus becomes rather expensive to train an effective model for text classification when it involves a large dataset of long documents. In this paper, we propose an active learning approach for text classification with lower annotation cost. Instead of scanning all the examples in the unlabeled data pool to select the best one for query, the proposed method automatically generates the most informative examples based on the classification model, and thus can be applied to tasks with large scale or even infinite unlabeled data. Furthermore, we propose to approximate the generated example with a few summary words by sparse reconstruction, which allows the annotators to easily assign the class label by reading a few words rather than the long document. Experiments on different datasets demonstrate that the proposed approach can effectively improve the classification performance while significantly reduce the annotation cost

    Strong Repulsive Forces between Protein and Oligo (Ethylene Glycol) Self-Assembled Monolayers: A Molecular Simulation Study

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    Restrained molecular dynamics simulations were performed to study the interaction forces of a protein with the self-assembled monolayers (SAMs) of S(CH(2))(4)(EG)(4)OH, S(CH(2))(11)OH, and S(CH(2))(11)CH(3) in the presence of water molecules. The force-distance curves were calculated by fixing the center of mass of the protein at several separation distances from the SAM surface. Simulation results show that the relative strength of repulsive force acting on the protein is in the decreasing order of OEG-SAMs > OH-SAMs > CH(3)-SAMs. The force contributions from SAMs and water molecules, the structural and dynamic behavior of hydration water, and the flexibility and conformation state of SAMs were also examined to study how water structure at the interface and SAM flexibility affect the forces exerted on the protein. Results show that a tightly bound water layer adjacent to the OEG-SAMs is mainly responsible for the large repulsive hydration force

    The Application of the Analytic Hierarchy Process and a New Correlation Algorithm to Urban Construction and Supervision Using Multi-Source Government Data in Tianjin

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    As the era of big data approaches, big data has attracted increasing amounts of attention from researchers. Various types of studies have been conducted and these studies have focused particularly on the management, organization, and correlation of data and calculations using data. Most studies involving big data address applications in scientific, commercial, and ecological fields. However, the application of big data to government management is also needed. This paper examines the application of multi-source government data to urban construction and supervision in Tianjin, China. The analytic hierarchy process and a new approach called the correlation degree algorithm are introduced to calculate the degree of correlation between different approval items in one construction project and between different construction projects. The results show that more than 75% of the construction projects and their approval items are highly correlated. The results of this study suggest that most of the examined construction projects are well supervised, have relatively high probabilities of satisfying the relevant legal requirements, and observe their initial planning schemes

    A Drosophila model of Pontocerebellar Hypoplasia reveals a critical role for the RNA exosome in neurons.

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    The RNA exosome is an evolutionarily-conserved ribonuclease complex critically important for precise processing and/or complete degradation of a variety of cellular RNAs. The recent discovery that mutations in genes encoding structural RNA exosome subunits cause tissue-specific diseases makes defining the role of this complex within specific tissues critically important. Mutations in the RNA exosome component 3 (EXOSC3) gene cause Pontocerebellar Hypoplasia Type 1b (PCH1b), an autosomal recessive neurologic disorder. The majority of disease-linked mutations are missense mutations that alter evolutionarily-conserved regions of EXOSC3. The tissue-specific defects caused by these amino acid changes in EXOSC3 are challenging to understand based on current models of RNA exosome function with only limited analysis of the complex in any multicellular model in vivo. The goal of this study is to provide insight into how mutations in EXOSC3 impact the function of the RNA exosome. To assess the tissue-specific roles and requirements for the Drosophila ortholog of EXOSC3 termed Rrp40, we utilized tissue-specific RNAi drivers. Depletion of Rrp40 in different tissues reveals a general requirement for Rrp40 in the development of many tissues including the brain, but also highlight an age-dependent requirement for Rrp40 in neurons. To assess the functional consequences of the specific amino acid substitutions in EXOSC3 that cause PCH1b, we used CRISPR/Cas9 gene editing technology to generate flies that model this RNA exosome-linked disease. These flies show reduced viability; however, the surviving animals exhibit a spectrum of behavioral and morphological phenotypes. RNA-seq analysis of these Drosophila Rrp40 mutants reveals increases in the steady-state levels of specific mRNAs and ncRNAs, some of which are central to neuronal function. In particular, Arc1 mRNA, which encodes a key regulator of synaptic plasticity, is increased in the Drosophila Rrp40 mutants. Taken together, this study defines a requirement for the RNA exosome in specific tissues/cell types and provides insight into how defects in RNA exosome function caused by specific amino acid substitutions that occur in PCH1b can contribute to neuronal dysfunction

    Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of <i>N</i>‑([1,2,4]Triazolo[4,3‑<i>a</i>]pyridin-3-yl)methane-sulfonamides as Potent and Selective <i>h</i>Na<sub>V</sub>1.7 Inhibitors for the Treatment of Pain

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    The sodium channel Na<sub>V</sub>1.7 has emerged as a promising target for the treatment of pain based on strong genetic validation of its role in nociception. In recent years, a number of aryl and acyl sulfonamides have been reported as potent inhibitors of Na<sub>V</sub>1.7, with high selectivity over the cardiac isoform Na<sub>V</sub>1.5. Herein, we report on the discovery of a novel series of <i>N</i>-([1,2,4]­triazolo­[4,3-<i>a</i>]­pyridin-3-yl)­methanesulfonamides as selective Na<sub>V</sub>1.7 inhibitors. Starting with the crystal structure of an acyl sulfonamide, we rationalized that cyclization to form a fused heterocycle would improve physicochemical properties, in particular lipophilicity. Our design strategy focused on optimization of potency for block of Na<sub>V</sub>1.7 and human metabolic stability. Lead compounds <b>10</b>, <b>13</b> (GNE-131), and <b>25</b> showed excellent potency, good <i>in vitro</i> metabolic stability, and low <i>in vivo</i> clearance in mouse, rat, and dog. Compound <b>13</b> also displayed excellent efficacy in a transgenic mouse model of induced pain

    Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of <i>N</i>‑([1,2,4]Triazolo[4,3‑<i>a</i>]pyridin-3-yl)methane-sulfonamides as Potent and Selective <i>h</i>Na<sub>V</sub>1.7 Inhibitors for the Treatment of Pain

    No full text
    The sodium channel Na<sub>V</sub>1.7 has emerged as a promising target for the treatment of pain based on strong genetic validation of its role in nociception. In recent years, a number of aryl and acyl sulfonamides have been reported as potent inhibitors of Na<sub>V</sub>1.7, with high selectivity over the cardiac isoform Na<sub>V</sub>1.5. Herein, we report on the discovery of a novel series of <i>N</i>-([1,2,4]­triazolo­[4,3-<i>a</i>]­pyridin-3-yl)­methanesulfonamides as selective Na<sub>V</sub>1.7 inhibitors. Starting with the crystal structure of an acyl sulfonamide, we rationalized that cyclization to form a fused heterocycle would improve physicochemical properties, in particular lipophilicity. Our design strategy focused on optimization of potency for block of Na<sub>V</sub>1.7 and human metabolic stability. Lead compounds <b>10</b>, <b>13</b> (GNE-131), and <b>25</b> showed excellent potency, good <i>in vitro</i> metabolic stability, and low <i>in vivo</i> clearance in mouse, rat, and dog. Compound <b>13</b> also displayed excellent efficacy in a transgenic mouse model of induced pain

    Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of <i>N</i>‑([1,2,4]Triazolo[4,3‑<i>a</i>]pyridin-3-yl)methane-sulfonamides as Potent and Selective <i>h</i>Na<sub>V</sub>1.7 Inhibitors for the Treatment of Pain

    No full text
    The sodium channel Na<sub>V</sub>1.7 has emerged as a promising target for the treatment of pain based on strong genetic validation of its role in nociception. In recent years, a number of aryl and acyl sulfonamides have been reported as potent inhibitors of Na<sub>V</sub>1.7, with high selectivity over the cardiac isoform Na<sub>V</sub>1.5. Herein, we report on the discovery of a novel series of <i>N</i>-([1,2,4]­triazolo­[4,3-<i>a</i>]­pyridin-3-yl)­methanesulfonamides as selective Na<sub>V</sub>1.7 inhibitors. Starting with the crystal structure of an acyl sulfonamide, we rationalized that cyclization to form a fused heterocycle would improve physicochemical properties, in particular lipophilicity. Our design strategy focused on optimization of potency for block of Na<sub>V</sub>1.7 and human metabolic stability. Lead compounds <b>10</b>, <b>13</b> (GNE-131), and <b>25</b> showed excellent potency, good <i>in vitro</i> metabolic stability, and low <i>in vivo</i> clearance in mouse, rat, and dog. Compound <b>13</b> also displayed excellent efficacy in a transgenic mouse model of induced pain
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