3,855 research outputs found

    \u3ci\u3eMutual Pharmaceutical Co. v. Bartlett\u3c/i\u3e and Its Implications

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    The authors state that the U.S. Supreme Court’s preemption ruling in Mutual Pharmaceutical Co. v. Bartlett, which generally shields generic drug manufacturers from state-law damages liability for design-defect claims, may also have broader implications for preemption jurisprudence. In this article they describe the Supreme Court’s decision in Mutual and evaluate how it may affect future products-liability litigation. Part I provides an overview of the case’s factual background and of federal generic drug regulation, while Part II discusses the Court’s majority opinion and the dissents. Part III analyzes the implications of the decision, offering ideas on how plaintiffs injured by defective or mislabeled generic prescription drugs may seek compensation after Mutual and how federal regulators and Congress may respond. Part III also briefly assesses Mutual’s potential impact on federal preemption doctrine

    Gearing Up: An Interim Report on the Sectoral Employment Initiative

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    Gearing Up is the first P/PV report on the Charles Stewart Mott Foundation's Sectoral Employment Initiative. It provides information about the various strategies being pursued, who is participating, and the sites' successes and struggles through the initiative's first two years. The report concludes with observations on those factors that appear critical to participating organizations' attaining their goals

    Experiences of Hope, Resilience and Spirituality in Kenyan Children and Adolescents

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    Resilience is a vital factor in overcoming adversity. The presence of hope and spiritual meaning have been demonstrated to contribute to resilience. Globally, there are millions of children and adolescents who have faced traumatic experiences including, but not limited to, the loss of their parents. The current study explored Kenyan children and adolescents’ experiences of resilience, hope and spirituality in the environment of a group home and school in Kenya. Mixed measures were utilized. Seventy-five participants ages 10-19 years old completed the quantitative measures including the CD-RISC, SEARS-C/A, the Children’s Hope scale, the Adult Hope scale, and a 1-item Spirituality measure. Out of those participants, 14 completed semi-structured interviews. Seven themes were extracted from the qualitative data including the following: adversity, meaning making of the past, community, role models, trust in something bigger than themselves, future plans, and religious coping. A series of correlations were conducted, and results found significant correlations between the children’s social resilience scale and the individual resilience scale (r(35) = .537, p = .001), the total Children’s hope scale and the SEARS-C total score (r(35) = .465, p = .005) and the CD-RISC and the Agency subscale of the Adult Hope scale (r(40) = .433, p = .005. This study contributes to the currently limited research in Kenya by examining the role resilience, hope and spirituality play in the experience of coping with loss for Kenyan children, specifically children and adolescents in a group home environment

    Full botanical inventory of the NPRA, 2019

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    Includes native, non-native, and invasive plant species identified in the NPRA in Spring 2019

    A Structural and Biochemical Analysis of the Drosophila Protein Period

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    Circadian clocks regulate changes in behavior and physiology that occur with a period of approximately 24 hours and are based on negative feedback loops. The molecular components of circadian clocks are conserved among animals, and a key element in all such clocks is the protein Period (PER), a circadian transcription inhibitor. The stable production, posttranslational modification, and nuclear translocation of PER all contribute to the timing of the clock. This work describes the synthesis and purification of various Drosophila PER fragments for biochemical and crystallographic analysis. Several stable PER fragments are identified, including one crystallizable fragment. The structure of the crystallized fragment is provided, and the implications of a critical intermolecular PER-PER interaction are explored. The crystallized region of PER includes the PAS (PER-ARNT-SIM) domain (230-512) as well as two subsequent helices (512-575). Unlike a previously published structure for a similar fragment [1], this structure shows a closed PER homodimer that relies on a flexible hydrophobic interaction between the final helix of one molecule and the PAS domain of its partner. Biochemical and mutational analyses of the crystallized fragment confirm the robust yet dynamic quality of this interaction. A critical residue in the dimerization interaction, Valine 243 is positioned at the center of the hydrophobic interface. Previous research has established that a lengthenedperiod phenotype in flies is caused by a point mutation at this residue, which changes the valine to asparitc acid [2]. Further studies have shown that the long period of flies bearing this mutation (perLong flies) results from a delay in the PER nuclear translocation [3]. Disruption of the hydrophobic molecular interface introduced by V243D suggests the delay in nuclear entry associated with perLong may be related to a defect in the PER self-binding interaction demonstrated in the crystal structure. The proximity of the observed PER-PER binding interface to the proposed PER-TIM binding interfaces also introduces the possibility that PER self binding may affect on the PER-TIM interaction. This work concludes with a proposed model for how disrupting the observed PER-PER intermolecular interaction may delay nuclear entry

    Bayesian inference of virus evolutionary models from next-generation sequencing data

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    There is a rich tradition in mathematical biology of modeling virus population dynamics within hosts. Such models can reproduce trends in the progression of viral infections such as HIV-1, and have also generated insights on the emergence of drug resistance and treatment strategies. Existing mathematical work has focused on the problem of predicting dynamics given model parameters. The problem of estimating model parameters from observed data has received little attention. One reason is likely the historical difficulty of obtaining high-resolution samples of virus diversity within hosts. Now, next-generation sequencing (NGS) approaches developed in the past decade can supply such data. This thesis presents two Bayesian methods that harness classical models to generate testable hypotheses from NGS datasets. The quasispecies equilibrium explains genetic variation in virus populations as a balance between mutation and selection. We use this model to infer fitness effects of individual mutations and pairs of interacting mutations. Although our method provides a high resolution and accurate picture of the fitness landscape when equilibrium holds, we demonstrate the common observation of populations with coexisting, divergent viruses is unlikely to be consistent with equilibrium. Our second statistical method estimates virus growth rates and binding affinity between viruses and antibodies using the generalized Lotka-Volterra model. Immune responses can explain coexistence of abundant virus variants and their trajectories through time. Additionally, we can draw inferences about immune escape and antibody genetic variants responsible for improved virus recognition
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