32 research outputs found

    What Legally Prescribed Functions Tell Us: Role Differences Between Adult and Juvenile Probation Officers

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    The authors\u27 current study, which is built on prior attempts to explore legally prescribed probation functions across 50 states and the District of Columbia, examines the statutorily prescribed duties of adult and juvenile probation officers in the past 10 years. Analyses of role shifts and the complementarities and differences that exist in the statutes are also explored

    A Possible Role for Metallic Ions in the Carbohydrate Cluster Recognition Displayed by a Lewis Y Specific Antibody

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    BACKGROUND:Lewis Y (Le(y)) is a blood group-related carbohydrate that is expressed at high surface densities on the majority of epithelial carcinomas and is a promising target for antibody-based immunotherapy. A humanized Le(y)-specific antibody (hu3S193) has shown encouraging safety, pharmacokinetic and tumor-targeting properties in recently completed Phase I clinical trials. METHODOLOGY/PRINCIPAL FINDINGS:We report the three-dimensional structures for both the free (unliganded) and bound (Le(y) tetrasaccharide) hu3S193 Fab from the same crystal grown in the presence of divalent zinc ions. There is no evidence of significant conformational changes occurring in either the Le(y) carbohydrate antigen or the hu3S193 binding site, which suggests a rigid fit binding mechanism. In the crystal, the hu3S193 Fab molecules are coordinated at their protein-protein interface by two zinc ions and in solution aggregation of Fab can be initiated by zinc, but not magnesium ions. Dynamic light scattering revealed that zinc ions could initiate a sharp transition from hu3S193 Fab monomers to large multimeric aggregates in solution. CONCLUSIONS/SIGNIFICANCE:Zinc ions can mediate interactions between hu3S193 Fab in crystals and in solution. Whether metallic ion mediated aggregation of antibody occurs in vivo is not known, but the present results suggest that similar clustering mechanisms could occur when hu3S193 binds to Le(y) on cells, particularly given the high surface densities of antigen on the target tumor cells

    Assessing the current state of juvenile probation practice: A statutory analysis

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    The 2002 Desktop Guide to Good Juvenile Probation Practice indicated that a state\u27s juvenile justice system should reflect a “balanced and restorative justice” (BARJ) model. Over a decade has passed since this publication, yet little is known about whether juvenile probation followed the BARJ. This study employed a statutory analysis to examine the differences between the legally prescribed roles of juvenile probation officers and the BARJ model across 50 states and the District of Columbia. Results indicated that even with significant reforms and statutory changes overtime, juvenile probation practices still fall short of meeting the basic tenets of restorative justice

    Visualizing inducible nitric-oxide synthase in living cells with a heme-binding fluorescent inhibitor

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    The study of nitric-oxide synthase (NOS) physiology is constrained by the lack of suitable probes to detect NOS in living cells or animals. Here, we characterized a fluorescent inducible NOS (iNOS) inhibitor called PIF (pyrimidine imidazole FITC) and examined its utility for microscopic imaging of iNOS in living cells. PIF binding to iNOS displayed high affinity, isoform selectivity, and heme specificity, and was essentially irreversible. PIF was used to successfully image iNOS expressed in RAW264.7 cells, HEK293T cells, human A549 epithelial cells, and freshly obtained human lung epithelium. PIF was used to estimate a half-life for iNOS of 1.8 h in HEK293T cells. Our work reveals that fluorescent probes like PIF will be valuable for studying iNOS cell biology and in understanding the pathophysiology of diseases that involve dysfunctional iNOS expression
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