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Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm3 to 62 mm3, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

ContributorsRutter, Erica (Author) / Stepien, Tracy (Author) / Anderies, Barrett (Author) / Plasencia, Jonathan (Author) / Woolf, Eric C. (Author) / Scheck, Adrienne C. (Author) / Turner, Gregory H. (Author) / Liu, Qingwei (Author) / Frakes, David (Author) / Kodibagkar, Vikram (Author) / Kuang, Yang (Author) / Preul, Mark C. (Author) / Kostelich, Eric (Author) / College of Liberal Arts and Sciences (Contributor)
Created2017-05-31
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Description

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

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.

ContributorsSantander, Javier (Author) / Kilbourne, Jacquelyn (Author) / Park, Jie Yeun (Author) / Martin, Taylor (Author) / Loh, Amanda (Author) / Diaz, Ignacia (Author) / Rojas, Robert (Author) / Segovia, Cristopher (Author) / DeNardo, Dale (Author) / Curtiss, Roy (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2014-08-01
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Description

A globally integrated carbon observation and analysis system is needed to improve the fundamental understanding of the global carbon cycle, to improve our ability to project future changes, and to verify the effectiveness of policies aiming to reduce greenhouse gas emissions and increase carbon sequestration. Building an integrated carbon observation

A globally integrated carbon observation and analysis system is needed to improve the fundamental understanding of the global carbon cycle, to improve our ability to project future changes, and to verify the effectiveness of policies aiming to reduce greenhouse gas emissions and increase carbon sequestration. Building an integrated carbon observation system requires transformational advances from the existing sparse, exploratory framework towards a dense, robust, and sustained system in all components: anthropogenic emissions, the atmosphere, the ocean, and the terrestrial biosphere. The paper is addressed to scientists, policymakers, and funding agencies who need to have a global picture of the current state of the (diverse) carbon observations.

We identify the current state of carbon observations, and the needs and notional requirements for a global integrated carbon observation system that can be built in the next decade. A key conclusion is the substantial expansion of the ground-based observation networks required to reach the high spatial resolution for CO2 and CH4 fluxes, and for carbon stocks for addressing policy-relevant objectives, and attributing flux changes to underlying processes in each region. In order to establish flux and stock diagnostics over areas such as the southern oceans, tropical forests, and the Arctic, in situ observations will have to be complemented with remote-sensing measurements. Remote sensing offers the advantage of dense spatial coverage and frequent revisit. A key challenge is to bring remote-sensing measurements to a level of long-term consistency and accuracy so that they can be efficiently combined in models to reduce uncertainties, in synergy with ground-based data.

Bringing tight observational constraints on fossil fuel and land use change emissions will be the biggest challenge for deployment of a policy-relevant integrated carbon observation system. This will require in situ and remotely sensed data at much higher resolution and density than currently achieved for natural fluxes, although over a small land area (cities, industrial sites, power plants), as well as the inclusion of fossil fuel CO2 proxy measurements such as radiocarbon in CO2 and carbon-fuel combustion tracers. Additionally, a policy-relevant carbon monitoring system should also provide mechanisms for reconciling regional top-down (atmosphere-based) and bottom-up (surface-based) flux estimates across the range of spatial and temporal scales relevant to mitigation policies. In addition, uncertainties for each observation data-stream should be assessed. The success of the system will rely on long-term commitments to monitoring, on improved international collaboration to fill gaps in the current observations, on sustained efforts to improve access to the different data streams and make databases interoperable, and on the calibration of each component of the system to agreed-upon international scales.

ContributorsCiais, P. (Author) / Dolman, A. J. (Author) / Bombelli, A. (Author) / Duren, R. (Author) / Peregon, A. (Author) / Rayner, P. J. (Author) / Miller, C. (Author) / Gobron, N. (Author) / Kinderman, G. (Author) / Marland, G. (Author) / Gruber, N. (Author) / Chevallier, F. (Author) / Andres, R. J. (Author) / Balsamo, G. (Author) / Bopp, L. (Author) / Breon, F. -M. (Author) / Broquet, G. (Author) / Dargaville, R. (Author) / Battin, T. J. (Author) / Borges, A. (Author) / Bovensmann, H. (Author) / Buchwitz, M. (Author) / Butler, J. (Author) / Canadell, J. G. (Author) / Cook, R. B. (Author) / DeFries, R. (Author) / Engelen, R. (Author) / Gurney, Kevin (Author) / Heinze, C. (Author) / Heimann, M. (Author) / Held, A. (Author) / Henry, M. (Author) / Law, B. (Author) / Luyssaert, S. (Author) / Miller, J. (Author) / Moriyama, T. (Author) / Moulin, C. (Author) / Myneni, R. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-11-30
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Description

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

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.

Created2014-07-31
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Description

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

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.

Created2014-08-01
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Description

Gompertz’s empirical equation remains the most popular one in describing cancer cell population growth in a wide spectrum of bio-medical situations due to its good fit to data and simplicity. Many efforts were documented in the literature aimed at understanding the mechanisms that may support Gompertz’s elegant model equation. One

Gompertz’s empirical equation remains the most popular one in describing cancer cell population growth in a wide spectrum of bio-medical situations due to its good fit to data and simplicity. Many efforts were documented in the literature aimed at understanding the mechanisms that may support Gompertz’s elegant model equation. One of the most convincing efforts was carried out by Gyllenberg and Webb. They divide the cancer cell population into the proliferative cells and the quiescent cells. In their two dimensional model, the dead cells are assumed to be removed from the tumor instantly. In this paper, we modify their model by keeping track of the dead cells remaining in the tumor. We perform mathematical and computational studies on this three dimensional model and compare the model dynamics to that of the model of Gyllenberg and Webb. Our mathematical findings suggest that if an avascular tumor grows according to our three-compartment model, then as the death rate of quiescent cells decreases to zero, the percentage of proliferative cells also approaches to zero. Moreover, a slow dying quiescent population will increase the size of the tumor. On the other hand, while the tumor size does not depend on the dead cell removal rate, its early and intermediate growth stages are very sensitive to it.

ContributorsAlzahrani, E. O. (Author) / Asiri, Asim (Author) / El-Dessoky, M. M. (Author) / Kuang, Yang (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-08-01
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Description

Errors in the specification or utilization of fossil fuel CO2 emissions within carbon budget or atmospheric CO2 inverse studies can alias the estimation of biospheric and oceanic carbon exchange. A key component in the simulation of CO2 concentrations arising from fossil fuel emissions is the spatial distribution of the emission

Errors in the specification or utilization of fossil fuel CO2 emissions within carbon budget or atmospheric CO2 inverse studies can alias the estimation of biospheric and oceanic carbon exchange. A key component in the simulation of CO2 concentrations arising from fossil fuel emissions is the spatial distribution of the emission near coastlines. Regridding of fossil fuel CO2 emissions (FFCO2) from fine to coarse grids to enable atmospheric transport simulations can give rise to mismatches between the emissions and simulated atmospheric dynamics which differ over land or water. For example, emissions originally emanating from the land are emitted from a grid cell for which the vertical mixing reflects the roughness and/or surface energy exchange of an ocean surface. We test this potential "dynamical inconsistency" by examining simulated global atmospheric CO2 concentration driven by two different approaches to regridding fossil fuel CO2 emissions. The two approaches are as follows: (1) a commonly used method that allocates emissions to grid cells with no attempt to ensure dynamical consistency with atmospheric transport and (2) an improved method that reallocates emissions to grid cells to ensure dynamically consistent results. Results show large spatial and temporal differences in the simulated CO2 concentration when comparing these two approaches. The emissions difference ranges from −30.3 TgC grid cell-1 yr-1 (−3.39 kgC m-2 yr-1) to +30.0 TgC grid cell-1 yr-1 (+2.6 kgC m-2 yr-1) along coastal margins. Maximum simulated annual mean CO2 concentration differences at the surface exceed ±6 ppm at various locations and times. Examination of the current CO2 monitoring locations during the local afternoon, consistent with inversion modeling system sampling and measurement protocols, finds maximum hourly differences at 38 stations exceed ±0.10 ppm with individual station differences exceeding −32 ppm. The differences implied by not accounting for this dynamical consistency problem are largest at monitoring sites proximal to large coastal urban areas and point sources. These results suggest that studies comparing simulated to observed atmospheric CO2 concentration, such as atmospheric CO2 inversions, must take measures to correct for this potential problem and ensure flux and dynamical consistency.

ContributorsZhang, X. (Author) / Gurney, Kevin (Author) / Rayner, P. (Author) / Liu, Y. (Author) / Asefi-Najafabady, Salvi (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-11-30
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Description

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

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.

ContributorsSimons, Ronald (Author) / Burt, Callie (Author) / Barr, Ashley B. (Author) / Lei, Man-Kit (Author) / Stewart, Eric (Author) / College of Public Service and Community Solutions (Contributor)
Created2014-11-01
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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),

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.

ContributorsNobles, Matt R. (Author) / Reyns, Bradford W. (Author) / Fox, Kate (Author) / Fisher, Bonnie S. (Author) / College of Public Service and Community Solutions (Contributor)
Created2013-11-30
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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 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.

ContributorsFox, Andrew M. (Author) / Katz, Charles (Author) / Choate, David (Author) / Hedberg, Eric (Author) / College of Public Service and Community Solutions (Contributor)
Created2015-01-02