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Supplementary Figure 3 from Evaluation of the Proteasome Inhibitor MLN9708 in Preclinical Models of Human Cancer

Supplementary Figure 1 from Evaluation of the Proteasome Inhibitor MLN9708 in Preclinical Models of Human Cancer

Supplementary Figure 2 from Evaluation of the Proteasome Inhibitor MLN9708 in Preclinical Models of Human Cancer

Bullying has attracted increased attention due to the serious implications for perpetrators, victims, and schools. Recent studies have sought to identify factors that may contribute to bullying perpetration, and child abuse has been identified as one such factor. The mediating processes linking child abuse to bullying perpetration, however, are not well understood. The current study explored adolescent mental health problems, including symptoms of depression, anxiety, dissociation, and posttraumatic stress disorder, and poor social skills as pathways between childhood abuse and adolescent bullying perpetration. Data for the current study are from the Longitudinal Studies of Child Abuse and Neglect. The current study utilized a longitudinal and multi-informant design in which adolescents reported their history of childhood abuse, mental health problems, and social skills when they were 12 years old; bullying perpetration was reported by adolescent's teachers when adolescents were 12 and 14. Results indicated childhood abuse was associated with higher levels of depression, anxiety, anger, dissociation, posttraumatic stress, and poor social skills. Only anxiety and poor social skills at age 12 were significantly associated with bullying perpetration when adolescents when were 14. Bootstrapped indirect effects from childhood abuse to bullying perpetration were significant for both anxiety and poor social skills, indicating full mediation. Addressing anxiety and poor social skills in early adolescence among children who have been abused may prevent bullying perpetration in mid-adolescence. Clinicians, teachers, and school administrators may desire to focus efforts on reducing anxiety and increasing social skills to mitigate bullying perpetration.

Childhood abuse has been widely associated with mental health problems in adulthood and marital quality may be one possible mediator. We examine marital quality as a mediator linking childhood abuse to positive affect, negative affect, emotionally reactivity, and aggression. Using data from Midlife Development in the United States (MIDUS), results of structural equation modeling indicate that the indirect effects from childhood abuse to each of the mental health outcomes were significant. Marital quality may be a source of resilience among adults who were abused in childhood and could be a point of intervention for clinicians.

This chapter examines the implementation of the Declaration Nostra Aetate, in particular through the work of the Secretariat for Non-Christians/Pontifical Council for Interreligious Dialogue (PCID), now the Dicastery for Interreligious Dialogue. Special attention is given to the documents produced by this dicastery: Dialogue and Mission (1984), Dialogue and Proclamation (1991), and Dialogue in Truth and Charity (2014). Mention is also made of an unpublished document on the spirituality of dialogue. The role of members of religious congregations is highlighted. The ecumenical dimension of the implementation of Nostra Aetate is evoked by recalling the cooperation of the PCID with the corresponding office in the World Council of Churches.

This article presents the concept that Space Elevators enable space solar power (SSP) architecture. An SSP constellation will significantly impact the climate change equation by slowing the increas...

Modern astronomy as a field of inquiry may be shaped by what we consider the “scientific” ways of knowing. However, the history of astronomy as a human endeavour dates back millennia before the “modern” notions of “science”. This long history means that astronomy is, at its core, built on a rich cultural diversity and history. This offers a rich potential that, while having been examined in various studies, has yet to be explored from a contextual pedagogical perspective. This paper offers an initial exploratory theoretical perspective on how social semiotics can be used to inform a conceptual framework. This approach not only brings notions of culture into the teaching and learning of astronomy but uses culture as the starting point in a way that does justice to the cultural diversity of the discipline and the world. In doing so, this paper develops two frameworks: (i) the Conceptual Framework for Culture in Astronomy Education and (ii) the Pedagogical Framework for Culture in Astronomy Education, both of these offer a novel approach to astronomy education.

Childhood maltreatment is associated with mental health problems across the life course and depression and social anxiety are two of the more common problems. Given the interpersonal nature of childhood maltreatment, adult romantic relationships have also been a keen interest. It has been suggested that the interpersonal relationships may mediate the relationship between maltreatment and adult mental health; however, little research has examined the mediating role of adult romantic relationships. This omission misses an opportunity to advance empirical understanding as well as clinical intervention. To address this gap, the current study utilized a sample of 785 adults using two waves of data from the study of Midlife of Development in the United States to examine relationship quality as a mediator linking childhood maltreatment to adult depressive and social anxiety symptoms. Interpretation of structural equation models indicated that there were significant indirect effects from childhood maltreatment to both symptoms of depressive and social anxiety through relationship quality. Results of post hoc analysis suggested that gender did not moderate any direct or indirect paths. In light of the significant indirect effects, relationship quality may be a point of intervention. Having a high-quality romantic relationship can provide a corrective experience for adults who were maltreated in childhood, thereby decreasing symptoms of depression and social anxiety.

Childhood maltreatment has well-established links to poorer marital functioning. Mindfulness has been shown to improve marital relationships and may buffer the effects of maltreatment. Using the Mi...

Liger is a second generation near-infrared imager and integral field spectrograph (IFS) for the W. M. Keck Observatory that will utilize the capabilities of the Keck All-sky Precision Adaptive-optics (KAPA) system. Liger operates at a wavelength range of 0.81 {\mu}m - 2.45 {\mu}m and utilizes a slicer and a lenslet array IFS with varying spatial plate scales and fields of view resulting in hundreds of modes available to the astronomer. Because of the high level of complexity in the raw data formats for the slicer and lenslet IFS modes, Liger must be designed in conjunction with a Data Reduction System (DRS) which will reduce data from the instrument in real-time and deliver science-ready data products to the observer. The DRS will reduce raw imager and IFS frames from the readout system and provide 2D and 3D data products via custom quick-look visualization tools suited to the presentation of IFS data. The DRS will provide the reduced data to the Keck Observatory Archive (KOA) and will be available to astronomers for offline post-processing of observer data. We present an initial design for the DRS and define the interfaces between observatory and instrument software systems., Comment: 12 pages, 4 figures, 2 tables

SummaryPersistent inflammation is a hallmark of HIV infection and is not reversed after suppression of viral replication by anti-retroviral therapy (ART). One explanation for chronic inflammation in ART-treated HIV-infected individuals is hyperreactivity of the myeloid cells due to a phenomenon called ‘trained immunity’. Here, we demonstrate that human monocyte derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, released increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect was associated with epigenetic changes related to inflammation and cholesterol metabolism pathways, upregulation of the lipid rafts, and was blocked by methyl-β-cyclodextrin, statin, and inhibitor of activity of lipid raft-associated receptor IGF1R. Bone marrow-derived macrophages from exNef-injected mice had higher abundance of lipid rafts and produced elevated levels of TNFα. These phenomena are consistent with trained immunity and may contribute to persistent inflammation and co-morbidities in HIV-infected individuals.

Background Childhood abuse is linked to experiencing multiple chronic health problems in midlife adults. Research has seldom examined whether childhood abuse is associated with a greater number of chronic physical health issues over time. The current study was to examine the contributions of childhood abuse on the development of chronic health conditions over a 10-year period. Participants and setting Data were taken from the study of Midlife Development in the United States. Using three waves of data, 661 married adults were included in the analysis. Results Using hierarchical regression, we found that childhood abuse was uniquely associated with the development of a greater number of chronic physical health conditions over a 10-year period. Post-hoc analysis found that neither gender nor age moderated the associations. Conclusions Findings of the study indicate that childhood abuse was uniquely associated with a greater number of chronic physical health conditions over a 10-year period. These findings suggest that abuse in childhood may speed up biological aging and erode adult’s health over time leaving adults vulnerable to chronic health conditions. Prevention efforts should assess adults for childhood abuse and the impact of childhood abuse on adult health over time may be preventable or more manageable.

Among adults, childhood maltreatment is widely known to increase depressive symptoms and reduce quality of adult’s intimate relationships. Considering the association between childhood maltreatment and adult depression and relationship quality from systemic theories may help clinicians conceptualize and intervene with their clients. Internal Family Systems is an evidenced based psychotherapy and is a trauma-informed model. Self is one of the core concepts of the Internal Family Systems model and it is theorized to reduce mental health problems such as depression and strengthen adult romantic relationships. Despite this theoretical proposition there is no supporting empirical research. To address this gap, the current study examined Self, specifically the qualities of Self (e.g., compassion) and Self-Leadership (e.g., staying calm in face of distress) as pathways linking childhood maltreatment to depression and relationship quality. Using a sample of adults in a romantic relationship, the current study examined Self-Qualities and Self-Leadership as mediators linking retrospective reports of child maltreatment to current depressive symptoms and relationship quality. Results indicate that the indirect (mediating) effects from childhood maltreatment to depressive symptoms and relationship quality were significant through Self-Qualities, but not Self-Leadership. Findings suggest that childhood maltreatment is associated with less frequent access to the qualities of Self, such as compassion and confidence which, in turn, were associated with fewer depressive symptoms and higher levels of relationship quality. For clinicians, the use of IFS and specifically helping clients increase the Self-Qualities may reduce depressive symptoms and strengthen romantic relationships.

Adults who were maltreated in childhood are at increased risk for depression, social anxiety, and loneliness in adulthood and spirituality may be a protective factor. The current study will extend ...

Internal Family Systems (IFS) is an effective model of psychotherapy. The central concept of IFS is the Self, characterized by compassion, calm, and courage. The Self is theorized to reduce adult m...

Childhood maltreatment is associated with mental and physical health problems across the life course. Marriages may be a risk factor for continued mental and physical health problems or, alternatively, they could buffer the effects of maltreatment severity on adult health. Using data from the study of Midlife Development in the United States (MIDUS), we evaluated marital support and strain as moderators of child maltreatment and adults’ subjective evaluations of physical and mental health in a sample of 760 married adults using the life course perspective. Results show that the interaction between childhood maltreatment severity and marital strain was associated with poorer physical health and was marginally associated with mental health. Marital support did not significantly interact with childhood maltreatment severity in predicting adult mental or physical health. Results suggest maltreatment and marital strain interact resulting in a greater accumulation of disadvantage leaving adults at risk for health problems.

Current chemotherapy against Mycobacterium tuberculosis (Mtb), an important human pathogen, requires a multidrug regimen lasting several months. While efforts have been made to optimize therapy by exploiting drug-drug synergies, testing new drug combinations in relevant host environments remains arduous. In particular, host environments profoundly affect the bacterial metabolic state and drug efficacy, limiting the accuracy of predictions based on in vitro assays alone. In this study, we utilize conditional Mtb knockdown mutants of essential genes as an experimentally-tractable surrogate for drug treatment, and probe the relationship between Mtb carbon metabolism and chemical-genetic interactions (CGI). We examined the anti-tubercular drugs isoniazid, rifampicin and moxifloxacin, and found that CGI are differentially responsive to the metabolic state, defining both environment-independent and –dependent interactions. Specifically, growth on the in vivo-relevant carbon source, cholesterol, reduced rifampicin efficacy by altering mycobacterial cell surface lipid composition. We report that a variety of perturbations in cell wall synthesis pathways restore rifampicin efficacy during growth on cholesterol, and that both environment-independent and cholesterol-dependent in vitro CGI could be leveraged to enhance bacterial clearance in the mouse infection model. Our findings present an atlas of novel chemical-genetic-environmental interactions that can be used to optimize drug-drug interactions as well as provide a framework for understanding in vitro correlates of in vivo efficacy.SignificanceEfforts to improve tuberculosis therapy include optimizing multi-drug regimens to take advantage of drug-drug synergies. However, the complex host environment has a profound effect on bacterial metabolic state and drug activity, making predictions of optimal drug combinations difficult. In this study, we leverage a newly developed library of conditional knockdown Mycobacterium tuberculosis mutants in which genetic depletion of essential genes mimics the effect of drug therapy. This tractable system allowed us to assess the effect of growth condition on predicted drug-drug interactions. We found that these interactions can be differentially sensitive to the metabolic state and select in vitro-defined interactions can be leveraged to accelerate bacterial killing during infection. These findings suggest new strategies for optimizing tuberculosis therapy.

Self-management programs improve health outcomes and self-management is recommended for chronic conditions. Yet chronic disease self-management supports have rarely been applied to people who use drugs (PWUD). Thus, our objective was to explore self-management experiences among marginalized PWUD. We used community-based participatory methods and conducted qualitative interviews. Participants self-identified as having long-term and past year experience using non-prescribed drugs, one other chronic condition, and socioeconomic marginalization. We analyzed the data using reflexive thematic analysis. Although many participants considered drug use a chronic health issue, self-medicating with non-prescribed drugs was also a key self-management strategy to address other health issues. Participants also described numerous other strategies, including cognitive and behavioral tactics. These findings highlight the need for a safe supply of pharmaceutical-grade drugs to support self-management among marginalized PWUD. Self-management supports should also be tailored to address relevant topics (e.g., harm reduction, withdrawal), include creative activities, and not hinder PWUD’s agency.

The interaction of Alfvén eigenmodes (AEs) and energetic particles is one of many important factors determining the success of future tokamaks. In JET, eight in-vessel antennas were installed to actively probe stable AEs with frequencies ranging 25–250 kHz and toroidal mode numbers |n| < 20. During the 2019–2020 deuterium campaign, almost 7500 resonances and their frequencies f 0, net damping rates γ < 0, and toroidal mode numbers were measured in almost 800 plasma discharges. From a statistical analysis of this database, continuum and radiative damping are inferred to increase with edge safety factor, edge magnetic shear, and when including non-ideal effects. Both stable AE observations and their associated damping rates are found to decrease with |n|. Active antenna excitation is also found to be ineffective in H-mode as opposed to L-mode; this is likely due to the increased edge density gradient’s effect on accessibility and ELM-related noise’s impact on mode identification. A novel measurement is reported of a marginally stable, edge-localized ellipticity-induced AE probed by the antennas during high-power auxiliary heating (ion cyclotron resonance heating and neutral beam injection) up to 25 MW. NOVA-K kinetic-MHD simulations show good agreement with experimental measurements of f 0, γ, and n, indicating the dominance of continuum and electron Landau damping in this case. Similar experimental and computational studies are planned for the recent hydrogen and ongoing tritium campaigns, in preparation for the upcoming DT campaign.

OBJECTIVES The Low Risk Ankle Rule (LRAR) can assist pediatric emergency department providers in reducing radiographs without missing significant fractures. Most providers are unaware of this tool. This study sought to educate providers about the LRAR then determine their self-reported use immediately and 2 months after education. METHODS A web-based survey was e-mailed to providers at one large pediatric emergency department. The survey assessed knowledge and use of the rule. Clinical scenarios, in which radiographs were not indicated, helped determine radiograph ordering practices. After a brief LRAR tutorial, respondents were requeried about radiograph ordering practices along with likelihood of future LRAR use. At 2 months, radiograph ordering was again assessed using the same scenarios; interim LRAR use was also determined. RESULTS Response rates on the initial and follow-up surveys were 61.4% and 96.2%, respectively. A minority (20%) had heard of the LRAR. Providers initially reported ordering radiographs on 84% of ankle injuries and 82.5% ordered radiographs in the scenario. Immediately after education, only 32% ordered a radiograph in the scenario; 85% reported that they would use the tool consistently. At 2 months, there was no significant change in radiograph ordering practices (79.5% vs 84%). In the interim, 30% reported using the rule at least once. CONCLUSIONS Most pediatric emergency department providers were unfamiliar with the LRAR. After a brief tutorial, most providers reported that planning to use the tool and self-reported radiograph ordering was significantly reduced; however, at 2 months, clinical practice was unaffected. Further work to implement the tool into practice is necessary.

Childhood maltreatment has been consistently associated with adult symptoms of depression, anxiety, and dissociation, and attachment has been proposed as one mediator. Attachment, however, tends to only partially mediate the association, and mindfulness may be another explanatory pathway. The current study examined mindfulness and attachment in a multiple mediator model linking maltreatment to adult symptoms of depression, anxiety, and dissociation. A sample of 232 adults were recruited from two universities and an online sample who completed an online survey. Using structural equation modeling, childhood maltreatment was indirectly associated to symptoms of depression (s = .104; 95% CI [.015, .193]), anxiety (s = .090; 95% CI [.014, .166]), and dissociation (s = .088; 95% CI [.006, .170]) through mindfulness. Additionally, childhood maltreatment was associated with symptoms of depression (s = .062; 95% CI [.007, .118]), anxiety (s = .074; 95% CI [.009, .139]), and dissociation (s = .069; 95% CI [.017, .121]) through attachment avoidance. No significant indirect effects were found through attachment anxiety. These findings indicate that both mindfulness and attachment may be explanatory pathways linking childhood maltreatment. Inclusion of both attachment and mindfulness provides a more robust theoretical understanding of how maltreatment is associated with adult mental health.

A possible explanation for chronic inflammation in HIV-infected individuals treated with anti-retroviral therapy is hyperreactivity of myeloid cells due to a phenomenon called "trained immunity." Here, we demonstrate that human monocyte-derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, release increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect is associated with chromatin changes at the genes involved in inflammation and cholesterol metabolism pathways and upregulation of the lipid rafts and is blocked by methyl-β-cyclodextrin, statin, and an inhibitor of the lipid raft-associated receptor IGF1R. Bone-marrow-derived macrophages from exNef-injected mice, as well as from mice transplanted with bone marrow from exNef-injected animals, produce elevated levels of tumor necrosis factor α (TNF-α) upon stimulation. These phenomena are consistent with exNef-induced trained immunity that may contribute to persistent inflammation and associated co-morbidities in HIV-infected individuals with undetectable HIV load.

Childhood maltreatment (CM) often occurs within the family system and can complicate familial relationships across the lifespan. Mental health problems may be one possible pathway linking CM to willingness to provide support and provisions of strain to family members. We advance this line of research by examining the degree to which CM shapes adults' understanding of how individual’s willingness to provide support to their family as well as enacted strain towards family members. Data were from the study of Midlife Development in the United States (MIDUS). Among the participants ( n = 568), the majority were White (91.2%), female (56.9%), and had a mean age of 51.5. Structural equation modeling was used to test the relationship between CM, depressive and social anxiety symptoms, and support and strain. Results indicate two key findings: (1) Maltreatment is directly related to higher provisions of strain and lower perceived availability to support family members; (2) Symptoms of depression and social anxiety mediated the effect from maltreatment to enactments of strain towards family members, whereas the same finding did not hold for availability of support. Only depressive symptoms were identified as a pathway. Because families frequently are a source of CM, yet may remain connected in adulthood, these findings offer nuanced implications for addressing mental health and family wellbeing among who have experienced CM.

In the past decade, exoplanet science has exploded, driven by discoveries using observations from both space-based and ground-based telescopes. Large amounts of data, coupled with technological advances and easy access to robotic telescopes, have allowed the general public and students to become vital contributors to the field. These developments have also provided fertile ground in the context of science education, by enabling exoplanet science to be taken into classrooms as an authentic scientific inquiry, echoing the notions of Science-as-Practice. This paper introduces technical infrastructure that enables beginners and students to quickly pick exoplanet targets and schedule an observation. It also provides a list of the “best” exoplanets to try and observe by month of the year (related to Right Ascension) and latitude (related to Declination).

The molecular ion H3 + is a potentially powerful tracer of the ionospheres and thermal structures of Jovian planets but has never been detected in a planetary mass object outside of the solar system. Models predict that H3 + emission driven by EUV flux and solar wind on hot Jupiters, or by powerful aurorae on brown dwarfs, will be between 102 and 105 × more intense than that of Jupiter. If optimal conditions for the production of emission do exist, the emission may be detectable by current ground-based instruments or in the near future. We present the first search for H3 + line emission in brown dwarfs with Keck Near Infrared Echelle Spectrograph L′ high-resolution spectroscopy. Additionally, we survey stars hosting giant planets at semimajor axes near 0.1–0.2 au, which models suggest may be the best planetary targets. No candidate H3 + emission is found. The limits we place on the emission of H3 + from brown dwarfs indicate that auroral generation of H3 + in these environments likely does not linearly scale from the processes found on Jupiter, plausibly due to deeper atmospheric penetration by precipitating auroral electrons. Detection of H3 + emission in brown dwarfs may be possible with the James Webb Space Telescope, or future 33 m class telescopes.

Introduction: EVT801 is a highly selective small molecule inhibitor of VEGFR3 and acts by inhibiting lymphangiogenesis and tumor angiogenesis in and around the tumor. It has shown compelling activity in a wide range of cancer models and is well-tolerated in preclinical toxicology studies. A phase I study is underway and will focus primarily on understanding the safety, tolerability, and pharmacokinetics of EVT801 across a range of doses. Methods: The first stage of the study is designed to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) for EVT801, with a second stage aiming to confirm RP2D in selected cancer patient populations. Clinical samples from these patients will be used to explore preliminary signals of clinical efficacy and investigate the biological activity of the drug using several biomarkers. Efficacy biomarkers will include imaging approaches (DCE-MRI and CEUS) to characterize tumor vascularization, as well as analysis of protein and mRNA quantification in on-treatment biopsies vs pre-treatment biopsies. Moreover, the relationship between activity of EVT801 and expression of key markers at protein and mRNA level will be investigated to potentially establish biomarkers for patient stratification and selection. Lastly, target engagement and pharmacodynamics effects will be investigated by immuno-monitoring as well as assessment of a defined set of proteins as markers of inflammation and angiogenesis as identified in preclinical in vivo models. We expect that these analyses will help to better understand the effects of the drug in human subjects and may also help to select the most responsive patients and provide early signs of clinical efficacy. Citation Format: Michael R. Paillasse, James Garner, Michael Fitzgerald, Lise Davenne, Pierre-Benoit Ancey, celine Poussereau-Pomie, Michael Esquerre, Gaelle Badet, Joel Tuyaret, Marie Mandron, Philippe Rochaix, Maha Ayyoub, Clara Maria Scarlata, Christine Ménétrier-Caux, Chrsitophe CAUX, Philippe Cassier, Jean-Pierre Delord, Carlos Gomez Roca, Pierre Fons. Cutting edge biomarkers strategy to provide early insights into activity of EVT-801, a novel selective VEGFR-3 inhibitor that targets tumor angiogenesis during the FIH clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3203.

Introduction: EVT801 is a highly selective, orally available VEGFR3 inhibitor that strongly inhibits angiogenesis without inducing hypoxia, considered one of the main causes of cancer-associated immunosuppression. EVT801 has shown compelling single agent efficacy in multiple in vivo models. In addition, combination of EVT801 and Immune Checkpoint Therapy (ICT) agents shows additive effects, and thus holds promise for combination treatment without induction of hypoxia-induced-immunosuppression. A phase I clinical trial is underway. Methods: The phase I trial will consist of two sequential stages. During the first stage, EVT801 will be administered to patients with advanced solid tumors in a multiple ascending dose study using an accelerated 3+3 design (1 patient per dose until grade 2 toxicities are observed) in up to 48 patients in 8 dose levels. The primary objective is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Stage 2 will focus on validation of this RP2D in two 6-patient cohorts diagnosed with soft tissue sarcoma or renal cell carcinoma. These patients will participate in intensive analyses involving several biomarkers to better understand the pharmacological activity of the drug. A potential third stage, consisting of a multiple ascending dose evaluation of the combination of EVT801 with immuno-oncology drugs, may be added to the ongoing trial, pending further technical discussions with physicians and regulators. In addition to conventional measures of safety, tolerability, efficacy, and pharmacokinetics, the phase I study will employ a rich suite of histological, immunological, and radiological biomarkers to provide early insights into the activity of EVT801. Citation Format: Carlos Gomez roca, Philippe Cassier, Marie Mandron, Myriam Estrabaut, Nathalie Delesque-Touchard, Adam C. Smith, Amy Klawitter, Leesa Gentry, Pierre Fons, Michael R. Paillasse, Lise Davenne, Michael Fitzgerald, James Garner, Jean-Pierre Delord. EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, started enrollment for its phase I first-in-human study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT206.

Experimental diagnostics, analysis tools and simulations represent particle distributions in various forms and coordinates. Algorithms to manage these data are needed on platforms like the ITER Integrated Modelling & Analysis Suite (IMAS), performing tasks such as archiving, modeling, conversion and visualization. A method that accomplishes some of the required tasks for distributions of charged particles with arbitrarily large magnetic drifts in axisymmetric tokamak geometry is described here. Given a magnetic configuration, we first construct a database of guiding center orbits, which serves as a basis for representing particle distributions. The orbit database contains the geometric information needed to perform conversions between arbitrary coordinates, modeling tasks, and resonance analyses. Using that database, an imported or newly modeled distribution is mapped to an exact equilibrium, where the dimensionality is reduced to three constants of motion (CoM). The orbit weight is uniquely given when the input is a true distribution: one that measures the number of physical particles per unit of phase space volume. Less ideal inputs, such as distributions estimated without drifts, or models of particle sources, can also be processed. As an application example, we reconstruct the drift-induced features of a distribution of fusion-born alpha particles in a large tokamak, given only a birth profile, which is not a function of the alpha's CoM. Repeated back-and-forth transformations between CoM space and energy-pitch-cylinder coordinates are performed for verification and as a proof of principle for IMAS., 27 pages, 21 figures

Our aesthetic response to the Universe, and the complexity of concepts through which we understand it, are inherently bound together in how we meaningfully interpret its nature. Over millennia the abstracted and intangible concepts of science have been developed and communicated through a rich array of representations across a variety of modes. The interpretation of such representations is a complex multidimensional and multimodal endeavor. This is particularly an issue in education where novices can struggle to engage with unfamiliar canonical representations. Learning in a discipline can be characterized as a process of developing disciplinary discernment in apprehending and using these representational systems. Using representations concerning the geometry of the Universe, evolution of the Universe, and cosmological expansion as examples, this paper provides an in-depth overview of the various multimodal representations through which concepts in cosmology are understood and communicated. In so doing this work unpacks the salient features of these representations in order to develop an underlying framework which we call the anatomy of representations (AOR). This study, in reviewing and analyzing representations in cosmology, explores this landscape of cosmology representations. This will allow for the characterization of how semiotic resources are mobilized, changed, and connections are made between various representational modes and levels, and an exploration of the landscape of cosmology and cosmology education. The AOR framework is intended as a guide for educators, including textbook authors, to support the development and interpretation of representations. (Less)