61 research outputs found

    Examining the New York State Gun Involved Violence Elimination Initiative’s Alignment with Several Theoretical Perspectives

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    This research examines how well New York State’s Gun Involved Violence Elimination (GIVE) initiative aligns with four theoretical domains: subculture of violence, deterrence, rational choice/situational crime prevention, and implementation theories. It reviews how procedural justice and community integration align with these theories and the evidence-based strategies that GIVE sites implement. Sites are grouped for analysis, and their characteristics are described. The literature review describes each theoretical domain’s core principles as they pertain to GIVE. It shows that the theories can be compatible and that their integration is difficult but would likely make the initiative more effective. The primary research questions pertain to how closely GIVE aligns with each of these theories, as well as whether sites with similar characteristics utilize these theoretical perspectives differently. The data collection and analysis methods are described. The analysis finds that theories and strategies that readily align with traditional law enforcement functions are the most likely to be fully adopted by law enforcement agencies, so street outreach strategies tend to be under-utilized while deterrence strategies are most embraced. Larger sites with higher shooting rates tend to have more comprehensive GIVE programs and align better with theory due to having gun violence problems characterized by subcultures of violence and other principles on which the strategies are built. However, medium sized sites tend to deliver strategies with effective dosage; larger sites struggle to deliver enough resources. GIVE implementation could be improved with more integration among strategies, community integration, and deeper recognition of the theoretical insights presented here

    Two Amino Acid Residues Contribute to a Cation-π Binding Interaction in the Binding Site of an Insect GABA Receptor

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    Cys-loop receptor binding sites characteristically possess an "aromatic box," where several aromatic amino acid residues surround the bound ligand. A cation-π interaction between one of these residues and the natural agonist is common, although the residue type and location are not conserved. Even in the closely related vertebrate GABA_A and GABA_C receptors, residues in distinct locations perform this role: in GABA_A receptors, a Tyr residue in loop A forms a cation-π interaction with GABA, while in GABA_C receptors it is a loop B residue. GABA-activated Cys-loop receptors also exist in invertebrates, where they have distinct pharmacologies and are the target of a range of pesticides. Here we examine the location of GABA in an insect binding site by incorporating a series of fluorinated Phe derivatives into the receptor binding pocket using unnatural amino acid mutagenesis, and evaluating the resulting receptors when expressed in Xenopus oocytes. A homology model suggests that two aromatic residues (in loops B and C) are positioned such that they could contribute to a cation-π interaction with the primary ammonium of GABA, and the data reveal a clear correlation between the GABA EC_(50) and the cation-π binding ability both at Phe206 (loop B) and Tyr254 (loop C), demonstrating for the first time the contribution of two aromatic residues to a cation-π interaction in a Cys-loop receptor

    No Tests Required: Comparing Traditional and Dynamic Predictors of Programming Success

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    Research over the past fifty years into predictors of programming performance has yielded little improvement in the identification of at-risk students. This is possibly because research to date is based upon using static tests, which fail to reflect changes in a student's learning progress over time. In this paper, the effectiveness of 38 traditional predictors of programming performance are compared to 12 new data-driven predictors, that are based upon analyzing directly logged data, describing the programming behavior of students. Whilst few strong correlations were found between the traditional predictors and performance, an abundance of strong significant correlations based upon programming behavior were found. A model based upon two of these metrics (Watwin score and percentage of lab time spent resolving errors) could explain 56.3% of the variance in coursework results. The implication of this study is that a student's programming behavior is one of the strongest indicators of their performance, and future work should continue to explore such predictors in different teaching contexts

    Rayleigh and S wave tomography constraints on subduction termination and lithospheric foundering in central California

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    The crust and upper mantle structure of central California have been modified by subduction termination, growth of the San Andreas plate boundary fault system, and small-scale upper mantle convection since the early Miocene. Here we investigate the contributions of these processes to the creation of the Isabella Anomaly, which is a high seismic velocity volume in the upper mantle. There are two types of hypotheses for its origin. One is that it is the foundered mafic lower crust and mantle lithosphere of the southern Sierra Nevada batholith. The alternative suggests that it is a fossil slab connected to the Monterey microplate. A dense broadband seismic transect was deployed from the coast to the western Sierra Nevada to fill in the least sampled areas above the Isabella Anomaly, and regional-scale Rayleigh and S wave tomography are used to evaluate the two hypotheses. New shear velocity (Vs) tomography images a high-velocity anomaly beneath coastal California that is sub-horizontal at depths of ∼40–80 km. East of the San Andreas Fault a continuous extension of the high-velocity anomaly dips east and is located beneath the Sierra Nevada at ∼150–200 km depth. The western position of the Isabella Anomaly in the uppermost mantle is inconsistent with earlier interpretations that the Isabella Anomaly is connected to actively foundering foothills lower crust. Based on the new Vs images, we interpret that the Isabella Anomaly is not the dense destabilized root of the Sierra Nevada, but rather a remnant of Miocene subduction termination that is translating north beneath the central San Andreas Fault. Our results support the occurrence of localized lithospheric foundering beneath the high elevation eastern Sierra Nevada, where we find a lower crustal low Vs layer consistent with a small amount of partial melt. The high elevations relative to crust thickness and lower crustal low Vs zone are consistent with geological inferences that lithospheric foundering drove uplift and a ∼3–4 Ma pulse of basaltic magmatism

    Multiple Tyrosine Residues Contribute to GABA Binding in the GABA_C Receptor Binding Pocket

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    The ligand binding site of Cys-loop receptors is dominated by aromatic amino acids. In GABA_C receptors, these are predominantly tyrosine residues, with a number of other aromatic residues located in or close to the binding pocket. Here we examine the roles of these residues using substitution with both natural and unnatural amino acids followed by functional characterization. Tyr198 (loop B) has previously been shown to form a cation−π interaction with GABA; the current data indicate that none of the other aromatic residues form such an interaction, although the data indicate that both Tyr102 and Phe138 may contribute to stabilization of the positively charged amine of GABA. Tyr247 (loop C) was very sensitive to substitution and, combined with data from a model of the receptor, suggest a π–π interaction with Tyr241 (loop C); here again functional data show aromaticity is important. In addition the hydroxyl group of Tyr241 is important, supporting the presence of a hydrogen bond with Arg104 suggested by the model. At position Tyr102 (loop D) size and aromaticity are important; this residue may play a role in receptor gating and/or ligand binding. The data also suggest that Tyr167, Tyr200, and Tyr208 have a structural role while Tyr106, Trp246, and Tyr251 are not critical. Comparison of the agonist binding site “aromatic box” across the superfamily of Cys-loop receptors reveals some interesting parallels and divergences

    GABA Binding to an Insect GABA Receptor: A Molecular Dynamics and Mutagenesis Study

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    RDL receptors are GABA-activated inhibitory Cys-loop receptors found throughout the insect CNS. They are a key target for insecticides. Here, we characterize the GABA binding site in RDL receptors using computational and electrophysiological techniques. A homology model of the extracellular domain of RDL was generated and GABA docked into the binding site. Molecular dynamics simulations predicted critical GABA binding interactions with aromatic residues F206, Y254, and Y109 and hydrophilic residues E204, S176, R111, R166, S176, and T251. These residues were mutated, expressed in Xenopus oocytes, and their functions assessed using electrophysiology. The data support the binding mechanism provided by the simulations, which predict that GABA forms many interactions with binding site residues, the most significant of which are cation-π interactions with F206 and Y254, H-bonds with E204, S205, R111, S176, T251, and ionic interactions with R111 and E204. These findings clarify the roles of a range of residues in binding GABA in the RDL receptor, and also show that molecular dynamics simulations are a useful tool to identify specific interactions in Cys-loop receptors

    Transatlantic collection of health informatics competencies

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    The electronic collection, processing and management of information is becoming increasingly important in healthcare. Because of the nature of the healthcare provision and delivery process, where the health, safety and quality of human lives are impacted on a daily basis, it is critical that those who work in the field are competent and able to perform all clinical, administrative, research and technology-impacted facets of their roles.The United States and the European Union have been working to encourage broader and more effective use of Information and Communications Technology (ICT) within healthcare. The development, use and governance of ICT within healthcare, often called health informatics, requires a number of competences which need to be identified and integrated into relevant skills assessment, education and training. Ultimately, this will help produce a more proficient and a more confident mobile health informatics-empowered workforce.A structured set of health information technology and eHealth implementation competences was collected in a co-operation project by voluntary experts in USA and European Union. The project took a deliberately broad starting point, seeking and reviewing an extensive range of related competencies. The skills cover the following domains of professions working with health information technology: direct patient care; administrative; engineering/information, communication, and technology (ICT); informatics; and research and biomedicine. The aggregation of over one thousand competencies was classified to a baseline set of skills and four levels of expertise in 33 focus areas according to Bloom’s taxonomy. The data set also contains definitions of 268 ‘typical’ professional roles. The use of the collection of competencies is supported by an open access web tool through which all the competencies can be searched through a query mechanism.The limitation of this work is that only the Acute Care segment of roles and competencies impacted by ICT was evaluated within the scope of this project, however, this subset of other care settings such as ambulatory, rehabilitative care, surgery, and others serves as a representative set of roles and competencies within the health care field as well as a being an important proof of concept for future usefulness of the work if extended beyond its current span. This project has made a contribution to the potential improvement of workforce mobility internationally

    Rayleigh and S wave tomography constraints on subduction termination and lithospheric foundering in central California

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    The crust and upper mantle structure of central California have been modified by subduction termination, growth of the San Andreas plate boundary fault system, and small-scale upper mantle convection since the early Miocene. Here we investigate the contributions of these processes to the creation of the Isabella Anomaly, which is a high seismic velocity volume in the upper mantle. There are two types of hypotheses for its origin. One is that it is the foundered mafic lower crust and mantle lithosphere of the southern Sierra Nevada batholith. The alternative suggests that it is a fossil slab connected to the Monterey microplate. A dense broadband seismic transect was deployed from the coast to the western Sierra Nevada to fill in the least sampled areas above the Isabella Anomaly, and regional-scale Rayleigh and S wave tomography are used to evaluate the two hypotheses. New shear velocity (Vs) tomography images a high-velocity anomaly beneath coastal California that is sub-horizontal at depths of ∼40–80 km. East of the San Andreas Fault a continuous extension of the high-velocity anomaly dips east and is located beneath the Sierra Nevada at ∼150–200 km depth. The western position of the Isabella Anomaly in the uppermost mantle is inconsistent with earlier interpretations that the Isabella Anomaly is connected to actively foundering foothills lower crust. Based on the new Vs images, we interpret that the Isabella Anomaly is not the dense destabilized root of the Sierra Nevada, but rather a remnant of Miocene subduction termination that is translating north beneath the central San Andreas Fault. Our results support the occurrence of localized lithospheric foundering beneath the high elevation eastern Sierra Nevada, where we find a lower crustal low Vs layer consistent with a small amount of partial melt. The high elevations relative to crust thickness and lower crustal low Vs zone are consistent with geological inferences that lithospheric foundering drove uplift and a ∼3–4 Ma pulse of basaltic magmatism
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