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Next, the nonstructural protein μNS of avian reoviruses was investigated using in vivo crystallization and serial femtosecond X-ray crystallography. Avian reoviruses infect poultry flocks causing significant economic losses. μNS is crucial in viral factory formation facilitating viral replication within host cells. Thus, structure-based targeting of μNS has the potential to disrupt intracellular viral propagation. Towards this goal, crystals of EGFP-tagged μNS (EGFP-μNS (448-605)) were produced in insect cells. The crystals diffracted to 4.5 Å at X-ray free electron lasers using viscous jets as crystal delivery methods and initial electron density maps were obtained. The resolution reported here is the highest described to date for μNS, which lays the foundation towards its structure determination.
Finally, structural, and functional studies of human Threonine aspartase 1 (Taspase1) were performed. Taspase1 is overexpressed in many liquid and solid malignancies. In the present study, using strategic circular permutations and X-ray crystallography, structure of catalytically active Taspase1 was resolved. The structure reveals the conformation of a 50 residues long fragment preceding the active side residue (Thr234), which has not been structurally characterized previously. This fragment adopted a straight helical conformation in contrast to previous predictions. Functional studies revealed that the long helix is essential for proteolytic activity in addition to the active site nucleophilic residue (Thr234) mediated proteolysis. Together, these findings enable a new approach for designing anti-cancer drugs by targeting the long helical fragment.
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Current research on criminal case processing typically examines a single decision-making point, so drawing reliable conclusions about the impact that factors such as defendants’ race or ethnicity exert across successive stages of the justice system is difficult. Using data from the New York County District Attorney's Office that tracks 185,275 diverse criminal cases, this study assesses racial and ethnic disparity for multiple discretionary points of prosecution and sentencing. Findings from multivariate logistic regression analyses demonstrate that the effects of race and ethnicity vary by discretionary point and offense category. Black and Latino defendants were more likely than White defendants to be detained, to receive a custodial plea offer, and to be incarcerated—and they received especially punitive outcomes for person offenses—but were more likely to benefit from case dismissals. The findings for Asian defendants were less consistent but suggest they were the least likely to be detained, to receive custodial offers, and to be incarcerated. These findings are discussed in the context of contemporary theoretical perspectives on racial bias and cumulative disadvantage in the justice system.
Background: Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the immunosignature as a diagnostic for spontaneous canine lymphoma at both at initial diagnosis and evaluating the disease free interval following treatment.
Methods: Sera from dogs with confirmed lymphoma (B cell n = 38, T cell n = 11) and clinically normal dogs (n = 39) were analyzed. Serum antibody responses were characterized by analyzing the binding pattern, or immunosignature, of serum antibodies on a non-natural sequence peptide microarray. Peptides were selected and tested for the ability to distinguish healthy dogs from those with lymphoma and to distinguish lymphoma subtypes based on immunophenotype. The immunosignature of dogs with lymphoma were evaluated for individual signatures. Changes in the immunosignatures were evaluated following treatment and eventual relapse.
Results: Despite being a clonal disease, both an individual immunosignature and a generalized lymphoma immunosignature were observed in each dog. The general lymphoma immunosignature identified in the initial set of dogs (n = 32) was able to predict disease status in an independent set of dogs (n = 42, 97% accuracy). A separate immunosignature was able to distinguish the lymphoma based on immunophenotype (n = 25, 88% accuracy). The individual immunosignature was capable of confirming remission three months following diagnosis. Immunosignature at diagnosis was able to predict which dogs with B cell lymphoma would relapse in less than 120 days (n = 33, 97% accuracy).
Conclusion: We conclude that the immunosignature can serve as a multilevel diagnostic for canine, and potentially human, lymphoma.
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Simons and Burt's (2011) social schematic theory (SST) of crime posits that adverse social factors are associated with offending because they promote a set of social schemas (i.e., a criminogenic knowledge structure) that elevates the probability of situational definitions favorable to crime. This study extends the SST model by incorporating the role of contexts for action. Furthermore, the study advances tests of the SST by incorporating a measure of criminogenic situational definitions to assess whether such definitions mediate the effects of schemas and contexts on crime. Structural equation models using 10 years of panel data from 582 African American youth provided strong support for the expanded theory. The results suggest that childhood and adolescent social adversity fosters a criminogenic knowledge structure as well as selection into criminogenic activity spaces and risky activities, all of which increase the likelihood of offending largely through situational definitions. Additionally, evidence shows that the criminogenic knowledge structure interacts with settings to amplify the likelihood of situational definitions favorable to crime.
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Cyberstalking is a relatively understudied area in criminology, with no consensus among scholars as to whether it represents a modified form of stalking or whether it is an entirely new and emerging criminal phenomenon. Using data from the 2006 Supplemental Victimization Survey (SVS) to the National Crime Victimization Survey (NCVS), this study compares stalking and cyberstalking victims across several dimensions, including situational features of their experiences and self-protective behaviors. Results indicate that there are significant differences between stalking and cyberstalking victims, including their number of self-protective behaviors adopted, duration of contact with their stalker, financial costs of victimization, and perceived fear at onset. Perceived fear over time, the occurrence of a physical attack, and sex of the victim were all associated with a higher number of self-protective behaviors for cyberstalking victims compared to stalking victims, net of the effect of the control variables. Implications for stalking theory, research, and criminal justice policy are discussed.
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The Phoenix TRUCE Project was modeled after the Chicago CeaseFire program. There have been relatively few process and impact evaluations on the model compared to the level of funding and attention the program has rendered. This paper presents findings related to the evaluation of the TRUCE project. We found that the program engaged in a strong media campaign, conducted conflict mediations, and identified high-risk individuals for case management. The program did not, however, establish a coordinated and collaborative relationship with the faith-based community or other community groups. Time-series analysis showed that program implementation corresponded to a significant decrease in overall levels of violence by more than 16 incidents on average per month, a decrease of 16 assaults on average per month, and resulted in a significant increase of 3.2 shootings on average per month, controlling for the comparison areas and the trends in the data.
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Research Summary:
Using U.S. Sentencing Commission data, this study assesses whether judicial downward departures are more prevalent among child pornography offenders compared with a matched sample of defendants convicted of other offenses. Additionally, we examine reasons given by judges when departing from the guidelines for these offenders. We found that child pornography defendants received significant reductions in sentences by way of judicial downward departures.
Policy Implications:
In 2007, the Supreme Court considerably altered the federal sentencing process. In Kimbrough v. United States (2007), the Court held that judicial departures were permissible on grounds of a policy disagreement. Many circuit courts have authorized sentencing judges to depart from the guidelines in child pornography cases based on such a policy disagreement. The findings of this study suggest that judicial downward departures for these offenders cannot be explained by individual characteristics, such as race, gender, or age, and may be indicative of a specific disagreement with this particular sentencing policy. An examination of the reasons provided by judges supports the hypothesis that judges may be attempting to remedy what they perceive as unjustly harsh sentencing guidelines.
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What's a profession without a code of ethics? Being a legitimate profession almost requires drafting a code and, at least nominally, making members follow it. Codes of ethics (henceforth “codes”) exist for a number of reasons, many of which can vary widely from profession to profession - but above all they are a form of codified self-regulation. While codes can be beneficial, it argues that when we scratch below the surface, there are many problems at their root. In terms of efficacy, codes can serve as a form of ethical window dressing, rather than effective rules for behavior. But even more that, codes can degrade the meaning behind being a good person who acts ethically for the right reasons.