37 research outputs found
An Analysis of Public Attitudes Toward the Insanity Defense
Results from a public opinion survey of knowledge, attitudes, and support for the insanity defense indicate that people dislike the insanity defense for both retributive and utilitarian reasons: they want insane law-breakers punished, and they believe that insanity defense procedures fail to protect the public. However, people vastly overestimate the use and success of the insanity plea. Several attitudinal and demographic variables that other researchers have found to be associated with people\u27s support for the death penalty and perceptions of criminal sentencing are also related to support for the insanity defense. Implications for public policy are discussed
White paper on nuclear astrophysics and low energy nuclear physics Part 1: Nuclear astrophysics
This white paper informs the nuclear astrophysics community and funding agencies about the scientific directions and priorities of the field and provides input from this community for the 2015 Nuclear Science Long Range Plan. It summarizes the outcome of the nuclear astrophysics town meeting that was held on August 21–23, 2014 in College Station at the campus of Texas A&M University in preparation of the NSAC Nuclear Science Long Range Plan. It also reflects the outcome of an earlier town meeting of the nuclear astrophysics community organized by the Joint Institute for Nuclear Astrophysics (JINA) on October 9–10, 2012 Detroit, Michigan, with the purpose of developing a vision for nuclear astrophysics in light of the recent NRC decadal surveys in nuclear physics (NP2010) and astronomy (ASTRO2010). The white paper is furthermore informed by the town meeting of the Association of Research at University Nuclear Accelerators (ARUNA) that took place at the University of Notre Dame on June 12–13, 2014. In summary we find that nuclear astrophysics is a modern and vibrant field addressing fundamental science questions at the intersection of nuclear physics and astrophysics. These questions relate to the origin of the elements, the nuclear engines that drive life and death of stars, and the properties of dense matter. A broad range of nuclear accelerator facilities, astronomical observatories, theory efforts, and computational capabilities are needed. With the developments outlined in this white paper, answers to long standing key questions are well within reach in the coming decade
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Cotton Irrigation Scheduling Using a Crop Growth Model and FAO-56 Methods: Field and Simulation Studies
Crop growth simulation models can address a variety of agricultural problems, but their use to directly assist in-season irrigation management decisions is less common. Confidence in model reliability can be increased if models are shown to provide improved in-season management recommendations, which are explicitly tested in the field. The objective of this study was to compare the CSM-CROPGRO-Cotton model (with recently updated ET routines) to a well-tested FAO-56 irrigation scheduling spreadsheet by (1) using both tools to schedule cotton irrigation during 2014 and 2015 in central Arizona and (2) conducting a post-hoc simulation study to further compare outputs from these tools. Two replications of each irrigation scheduling treatment and a water-stressed treatment were established on a 2.6 ha field. Irrigation schedules were developed on a weekly basis and administered via an overhead lateral-move sprinkler irrigation system. Neutron moisture meters were used weekly to estimate soil moisture status and crop water use, and destructive plant samples were routinely collected to estimate cotton leaf area index (LAI) and canopy weight. Cotton yield was estimated using two mechanical cotton pickers with differing capabilities: (1) a two-row picker that facilitated manual collection of yield samples from 32 m(2) areas and (2) a four-row picker equipped with a sensor-based cotton yield monitoring system. In addition to statistical testing of field data via mixed models, the data were used for post-hoc reparameterization and fine-tuning of the irrigation scheduling tools. Post-hoc simulations were conducted to compare measured and simulated evapotranspiration, crop coefficients, root zone soil moisture depletion, cotton growth metrics, and yield for each irrigation treatment. While total seasonal irrigation amounts were similar among the two scheduling tools, the crop model recommended more water during anthesis and less during the early season, which led to higher cotton fiber yield in both seasons (p < 0.05). The tools calculated cumulative evapotranspiration similarly, with root mean squared errors (RMSEs) less than 13%; however, FAO-56 crop coefficient (K-c) plots demonstrated subtle differences in daily evapotranspiration calculations. Root zone soil moisture depletion was better calculated by CSM-CROPGRO-Cotton, perhaps due to its more complex soil profile simulation; however, RMSEs for depletion always exceeded 20% for both tools and reached 149% for the FAO-56 spreadsheet in 2014. CSM-CROPGRO-Cotton simulated cotton LAI, canopy weight, canopy height, and yield with RMSEs less than 21%, while the FAO-56 spreadsheet had no capability for such outputs. Through field verification and thorough post-hoc data analysis, the results demonstrated that the CSM-CROPGRO-Cotton model with updated FAO-56 ET routines could match or exceed the accuracy and capability of an FAO-56 spreadsheet tool for cotton water use calculations and irrigation scheduling.Cotton IncorporatedThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
The vibrator Mutation Causes Neurodegeneration via Reduced Expression of PITPα: Positional Complementation Cloning and Extragenic Suppression
AbstractThe mouse vibrator mutation causes an early-onset progressive action tremor, degeneration of brain stem and spinal cord neurons, and juvenile death. We cloned the vibrator mutation using an in vivo positional complementation approach and complete resequencing of the resulting 76 kb critical region from vibrator and its parental chromosome. The mutation is an intracisternal A particle retroposon insertion in intron 4 of the phosphatidylinositol transfer protein α gene, causing a 5-fold reduction in RNA and protein levels. Expression of neurofilament light chain is also reduced in vibrator, suggesting one signaling pathway that may underlie vibrator pathology. The vibrator phenotype is suppressed in one intercross. We performed a complete genome scan and mapped a major suppressor locus (Mvb-1) to proximal chromosome 19
Ena/VASP Is Required for Neuritogenesis in the Developing Cortex
Mammalian cortical development involves neuronal migration and neuritogenesis; this latter process forms the structural precursors to axons and dendrites. Elucidating the pathways that regulate the cytoskeleton to drive these processes is fundamental to our understanding of cortical development. Here we show that loss of all three murine Ena/VASP proteins, a family of actin regulatory proteins, causes neuronal ectopias, alters intralayer positioning in the cortical plate, and, surprisingly, blocks axon fiber tract formation during corticogenesis. Cortical fiber tract defects in the absence of Ena/VASP arise from a failure in neurite initiation, a prerequisite for axon formation. Neurite initiation defects in Ena/VASP-deficient neurons are preceded by a failure to form bundled actin filaments and filopodia. These findings provide insight into the regulation of neurite formation and the role of the actin cytoskeleton during cortical development.Anna Fuller Foundation (Predoctoral Fellowship)Virginia and Daniel K. Ludwig Graduate FellowshipNational Institutes of Health (U.S.) (Grant F32-NS45366)Stanley Medical Research InstituteNational Institutes of Health (U.S.) (Grant GM58801)National Institutes of Health (U.S.) (Grant U54 GM064346