Electron gun using coniferous carbon nano-structure

We have measured the emission stability of a coniferous carbon nano-structure (CCNS) field emis-sion electron source. Stable emission over the 1274 h measurement was observed at an emission current density of 20 mA·cm−2. The CCNS emitter can generate an emission current of more than 10 mA making it a practical choice for many applications requiring high electron current. For exam-ple, we are currently developing a CCNS based electron gun for electron accelerators and a portable X-ray source. Recent progress on both these applications is presented. 1

Effects of grid spacing on high-frequency precipitation variance in coupled high-resolution global ocean–atmosphere models

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Light, C., Arbic, B., Martin, P., Brodeau, L., Farrar, J., Griffies, S., Kirtman, B., Laurindo, L., Menemenlis, D., Molod, A., Nelson, A., Nyadjro, E., O’Rourke, A., Shriver, J., Siqueira, L., Small, R., & Strobach, E. Effects of grid spacing on high-frequency precipitation variance in coupled high-resolution global ocean–atmosphere models. Climate Dynamics, (2022): 1–27, https://doi.org/10.1007/s00382-022-06257-6.High-frequency precipitation variance is calculated in 12 different free-running (non-data-assimilative) coupled high resolution atmosphere–ocean model simulations, an assimilative coupled atmosphere–ocean weather forecast model, and an assimilative reanalysis. The results are compared with results from satellite estimates of precipitation and rain gauge observations. An analysis of irregular sub-daily fluctuations, which was applied by Covey et al. (Geophys Res Lett 45:12514–12522, 2018. https://doi.org/10.1029/2018GL078926) to satellite products and low-resolution climate models, is applied here to rain gauges and higher-resolution models. In contrast to lower-resolution climate simulations, which Covey et al. (2018) found to be lacking with respect to variance in irregular sub-daily fluctuations, the highest-resolution simulations examined here display an irregular sub-daily fluctuation variance that lies closer to that found in satellite products. Most of the simulations used here cannot be analyzed via the Covey et al. (2018) technique, because they do not output precipitation at sub-daily intervals. Thus the remainder of the paper focuses on frequency power spectral density of precipitation and on cumulative distribution functions over time scales (2–100 days) that are still relatively “high-frequency” in the context of climate modeling. Refined atmospheric or oceanic model grid spacing is generally found to increase high-frequency precipitation variance in simulations, approaching the values derived from observations. Mesoscale-eddy-rich ocean simulations significantly increase precipitation variance only when the atmosphere grid spacing is sufficiently fine (< 0.5°). Despite the improvements noted above, all of the simulations examined here suffer from the “drizzle effect”, in which precipitation is not temporally intermittent to the extent found in observations.Support for CXL’s effort on this project was provided by a Research Experiences for Undergraduates (REU) supplement for National Science Foundation (NSF) grant OCE-1851164 to BKA, which also provided partial support for PEM. In addition, BKA acknowledges NSF grant OCE-1351837, which provided partial support for AKO, Office of Naval Research grant N00014-19-1-2712 and NASA grants NNX17AH55G, which also provided partial support for ADN, and 80NSSC20K1135. JTF’s participation, and the SPURS-II buoy data, were funded by NASA grants 80NSSC18K1494 and NNX15AG20G

Deranged sodium to sudden death

In February 2014, a group of scientists convened as part of the University of California Davis Cardiovascular Symposium to bring together experimental and mathematical modelling perspectives and discuss points of consensus and controversy on the topic of sodium in the heart. This paper summarizes the topics of presentation and discussion from the symposium, with a focus on the role of aberrant sodium channels and abnormal sodium homeostasis in cardiac arrhythmias and pharmacotherapy from the subcellular scale to the whole heart. Two following papers focus on Na⁺ channel structure, function and regulation, and Na⁺/Ca²⁺ exchange and Na⁺/K⁺ ATPase. The UC Davis Cardiovascular Symposium is a biannual event that aims to bring together leading experts in subfields of cardiovascular biomedicine to focus on topics of importance to the field. The focus on Na⁺ in the 2014 symposium stemmed from the multitude of recent studies that point to the importance of maintaining Na⁺ homeostasis in the heart, as disruption of homeostatic processes are increasingly identified in cardiac disease states. Understanding how disruption in cardiac Na⁺-based processes leads to derangement in multiple cardiac components at the level of the cell and to then connect these perturbations to emergent behaviour in the heart to cause disease is a critical area of research. The ubiquity of disruption of Na⁺ channels and Na⁺ homeostasis in cardiac disorders of excitability and mechanics emphasizes the importance of a fundamental understanding of the associated mechanisms and disease processes to ultimately reveal new targets for human therapy.Centro de Investigaciones Cardiovasculare

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Human values and the value of humanities in interdisciplinary research

Research integrating the perspectives of different disciplines, or interdisciplinary research, has become increasingly common in academia and is considered important for its ability to address complex questions and problems. This mode of research aims to leverage differences among disciplines in generating a more complex understanding of the research landscape. To interact successfully with other disciplines, researchers must appreciate their differences, and this requires recognizing how the research landscape looks from the perspective of other disciplines. One central aspect of these disciplinary perspectives involves values, and more specifically, the roles that values do, may, and should play in research practice. It is reasonable to think that disciplines differ in part because of the different views that their practitioners have on these roles. This paper represents a step in the direction of evaluating this thought. Operating at the level of academic branches, which comprise relevantly similar disciplines (e.g. social and behavioral sciences), this paper uses quantitative techniques to investigate whether academic branches differ in terms of views on the impact of values on research. Somewhat surprisingly, we find very little relation between differences in these views and differences in academic branch. We discuss these findings from a philosophical perspective to conclude the paper

Attributions for ambiguity in a treatment- decision context can create ambiguity aversion or seeking

The phenomenon of ambiguity aversion suggests that people prefer options that offer precisely rather than imprecisely known chances of success. However, past work on people’s responses to ambiguity in health treatment contexts found ambiguity seeking rather than aversion. The present work addressed whether such findings reflected a broad tendency for ambiguity seeking in health treatment contexts or whether specific attributions for ambiguity play a substantial role. In three studies, people choose between two treatment options that involved similar underlying probabilities, except that the probabilities for one option involved ambiguity. The attributions offered for the ambiguity played an important role in the results. For example, when the range of probabilities associated with an ambiguous treatment was attributed to the fact that different studies yield different results, participants tended to show ambiguity aversion or indifference. However, when the range was attributed to something that participants could control (e.g., regular application of a cream) or something about which they were overoptimistic (e.g., their immune system function), participants tended to show ambiguity seeking. Health professionals should be mindful of how people will interpret and use information about ambiguity when choosing among treatments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171119/1/bdm2249_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171119/2/bdm2249.pd

Attributions for ambiguity in a treatment‐decision context can create ambiguity aversion or seeking

The phenomenon of ambiguity aversion suggests that people prefer options that offer precisely rather than imprecisely known chances of success. However, past work on people’s responses to ambiguity in health treatment contexts found ambiguity seeking rather than aversion. The present work addressed whether such findings reflected a broad tendency for ambiguity seeking in health treatment contexts or whether specific attributions for ambiguity play a substantial role. In three studies, people choose between two treatment options that involved similar underlying probabilities, except that the probabilities for one option involved ambiguity. The attributions offered for the ambiguity played an important role in the results. For example, when the range of probabilities associated with an ambiguous treatment was attributed to the fact that different studies yield different results, participants tended to show ambiguity aversion or indifference. However, when the range was attributed to something that participants could control (e.g., regular application of a cream) or something about which they were overoptimistic (e.g., their immune system function), participants tended to show ambiguity seeking. Health professionals should be mindful of how people will interpret and use information about ambiguity when choosing among treatments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171119/1/bdm2249_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171119/2/bdm2249.pd