The Manson impact structure, a possible site for a Cretaceous-Tertiary (K-T) boundary impact

The Manson impact structure, about 35 km in diameter, is the largest impact crater recognized in the United States. Its center is located near the town of Manson, 29 km west of Fort Dodge, Iowa. The structure is not well known geologically because it is covered by tens of meters of glacial deposits. What is known about the structure was learned mostly from the study of water well cuttings. At Manson the normal Phanerozoic and Proterozoic sedimentary rocks were replaced by centrally uplifted Proterozoic crystalline rocks that are representative of the normal basement: This central uplift is surrounded by completely disrupted rocks which are roughly encircled by peripherally faulted and slumped sequences of normal sedimentary strata. Radially outward normal sedimentary strata are uplifted slightly. Manson, once interpreted as a cryptovolcanic structure, is now considered an impact structure based on its circular shape, its central uplift and the presence of multiple intersecting sets of shock lamellae in quartz grains from the central uplift. The Ar-40/Ar-39 age spectrum dating results for a microcline separate from the Manson 2-A core in the central uplift is shown. This spectrum is interpreted to indicate a nearly complete degassing of the microcline at the time of the Manson impact. The remainder of the gas released climbs in age with increasing temperature of release. This pattern of the age spectrum is interpreted to represent diffusional loss due to reheating at the time of the impact and during subsequent cooling. Shocked quartz grains, present in the iridium-bearing layer at the K-T boundary throughout the world, have a significantly larger size and are more abundant in the western interior of North America than elsewhere in the world. Furthermore, shocked feldspar and granitic fragments are found at the K-T boundary in North America. These observations indicate the K-T boundary impact must have penetrated continental crust in North America

Preliminary Ar-40/Ar-39 age spectrum and laser probe dating of the M1 core of the Manson Impact Structure, Iowa: A K-T boundary crater candidate

Preliminary Ar-40/Ar-39 age spectrum and laser probe dating results from new drill core from the 35-km-diameter Manson Impact Structure (MIS), Iowa indicates a reasonable possibility that the MIS is a Cretaceous-Tertiary (K-T) boundary impact event. Several different types of samples from a melt-matrix breccia, a unit of apparent crater fill intersected by the M1 core, were analyzed. Ar-40/Ar-39 results from these samples indicate a maximum age for the MIS of about 65.4 plus or minus 0.4(2 sigma) Ma. Petrographic analyses of the samples indicate a high probability that all the dated samples from the melt-matrix breccia contain relict grains that were not entirely melted or degassed at the time of impact, suggesting that the actual age of the MIS could be somewhat younger than our preliminary results indicate. The results are consistent with a previously published age estimate of shocked microcline from the MIS central uplift of 65.7 plus or minus 1.0 Ma

Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines : a case report

Abstract Background Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. Methods Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-γ+ T cell responses against vaccine peptides in peripheral blood after 12, 17 and 34 vaccinations by analyzing T-cell receptor (TCR) repertoire diversity and epitope-binding regions of peptide-reactive T-cell lines and clones. By restricting analysis to sorted IFN-γ-producing T cells we could assure epitope-specificity, functionality, and TH1 polarization. Results A peptide-specific T-cell response against three of the four vaccine peptides could be detected sequentially. Molecular TCR analysis revealed a broad vaccine-reactive TCR repertoire with clones of discernible specificity. Four identical or convergent TCR sequences could be identified at more than one time-point, indicating timely persistence of vaccine-reactive T cells. One dominant TCR expressing a dual TCRVα chain could be found in three T-cell clones. The observed T-cell responses possibly contributed to clinical outcome: The patient is alive 6 years after initial diagnosis and in complete remission for 4 years now. Conclusions Therapeutic vaccination with a neoantigen-derived four-peptide vaccine resulted in a diverse and long-lasting immune response against these targets which was associated with prolonged clinical remission. These data warrant confirmation in a larger proof-of concept clinical trial

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

Environmental Influences on Disabled Students\u27 Cocurricular Involvement

Involvement of students in the cocurriculum is critical to the development of desired outcomes in college. However, the literature on disabled college students centers academic experiences, largely overlooking cocurricular experiences. In this study, we explored the cocurricular involvement of disabled students, examining factors that created barriers for their involvement, how students responded to barriers, factors that made involvement possible, and those that encouraged involvement. Grounded in a critical realist approach to disability, augmented by environmental theories, and employing a descriptive-interpretive design, we used both individual interviews and focus groups to obtain data from 33 disabled students at a midwestern, comprehensive, land-grant university. We found that (a) other people\u27s behaviors and attitudes created more barriers to disabled students\u27 involvement than did physical or organizational factors; (b) participants reported a wide variety of emotional and behavioral responses to the barriers; (c) accessible physical design, flexible organizational policies, and assistance from others made involvement possible; (d) universally designed elements of the physical and organizational environment as well as active support from staff and peers encouraged involvement; and (e) barriers to and encouragers of involvement varied by impairment. We offer implications for further research and practice