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This can make mutation detection difficult; and while increasing sequencing depth
can often help, sequence-specific errors and other non-random biases cannot be de-
tected by increased depth. The problem of accurate genotyping is exacerbated when
there is not a reference genome or other auxiliary information available.
I explore several methods for sensitively detecting mutations in non-model or-
ganisms using an example Eucalyptus melliodora individual. I use the structure of
the tree to find bounds on its somatic mutation rate and evaluate several algorithms
for variant calling. I find that conventional methods are suitable if the genome of a
close relative can be adapted to the study organism. However, with structured data,
a likelihood framework that is aware of this structure is more accurate. I use the
techniques developed here to evaluate a reference-free variant calling algorithm.
I also use this data to evaluate a k-mer based base quality score recalibrator
(KBBQ), a tool I developed to recalibrate base quality scores attached to sequencing
data. Base quality scores can help detect errors in sequencing reads, but are often
inaccurate. The most popular method for correcting this issue requires a known
set of variant sites, which is unavailable in most cases. I simulate data and show
that errors in this set of variant sites can cause calibration errors. I then show that
KBBQ accurately recalibrates base quality scores while requiring no reference or other
information and performs as well as other methods.
Finally, I use the Eucalyptus data to investigate the impact of quality score calibra-
tion on the quality of output variant calls and show that improved base quality score
calibration increases the sensitivity and reduces the false positive rate of a variant
calling algorithm.
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Pathways of Distinction Analysis of Liver Cancer Data: Genetic Differences Between Males and Females
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Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to understand the mechanism of interaction.
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Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.
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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.
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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.