Future Missions to Titan: Scientific and Engineering Challenges

Saturn’s largest moon, Titan, has been an enigma at every stage of its exploration. For three decades after the hazy atmosphere was discovered from the ground in the 1940s, debate ensued over whether it was a thin layer of methane or a dense shield of methane and nitrogen. Voyager 1 settled the matter in favor of the latter in 1980, but the details of the thick atmosphere discovered raised even more intriguing questions about the nature of the hidden surface, and the sources of resupply of methane to the atmosphere. The simplest possibility, that an ocean of methane and its major photochemical product ethane might cover the globe, was cast in doubt by Earth-based radar studies and then eliminated by Hubble Space Telescope and adaptive optics imaging in the near-infrared from large ground-based telescopes in the 1990s. These data, however, did not reveal the complexity of the surface that Cassini-Huygens would uncover beginning in 2004. A hydrological cycle appears to exist in which methane (in concert with ethane in some processes) plays the role on Titan that water plays on Earth. Channels likely carved by liquid methane and/or ethane, lakes and seas of these materials—some rivaling or exceeding North America’s Great Lakes in size—vast equatorial dune fields of complex organics made high in the atmosphere and shaped by wind, and intriguing hints of geologic activity suggest a world with a balance of geologic and atmospheric processes that is the solar system’s best analogue to Earth. Deep underneath Titan’s dense atmosphere and active, diverse surface is an interior ocean discovered by Cassini and thought to be largely composed of liquid water. Cassini-Huygens has provided spectacular data and has enabled us to glimpse the mysterious surface of Titan. However the mission will leave us with many questions that require future missions to answer. These include determining the composition of the surface and the geographic distribution of various organic constituents. Key questions remain about the ages of surface features, specifically whether cryovolcanism and tectonism are actively ongoing or are relics of a more active past. Ammonia, circumstantially suggested to be present by a variety of different kinds of Cassini-Huygens data, has yet to be seen. Is methane out-gassing from the interior or ice crust today? Are the lakes fed primarily by rain or underground methane-ethane aquifers (more properly, “alkanofers”) and how often have heavy methane rains come to the equatorial region? We should investigate whether Titan’s surface supported vaster seas of methane in the past, and whether complex self-organizing chemical systems have come and gone in the water volcanism, or even exist in exotic form today in the high latitude lakes. The presence of a magnetic field has yet to be established. A large altitude range in the atmosphere, from 400–900 km in altitude, will remain poorly explored after Cassini. Much remains to be understood about seasonal changes of the atmosphere at all levels, and the long-term escape of constituents to space. Other than Earth, Titan is the only world in our solar system known to have standing liquids and an active “hydrologic cycle” with clouds, rains, lakes and streams. The dense atmosphere and liquid lakes on Titan’s surface can be explored with airborne platforms and landed probes, but the key aspect ensuring the success of future investigations is the conceptualization and design of instruments that are small enough to fit on the landed probes and airborne platforms, yet sophisticated enough to conduct the kinds of detailed chemical (including isotopic), physical, and structural analyses needed to investigate the history and cycling of the organic materials. In addition, they must be capable of operating at cryogenic temperatures while maintaining the integrity of the sample throughout the analytic process. Illuminating accurate chemistries also requires that the instruments and tools are not simultaneously biasing the measurements due to localized temperature increases. While the requirements for these techniques are well understood, their implementation in an extremely low temperature environment with limited mass, power and volume is acutely challenging. No such instrument systems exist today. Missions to Titan are severely limited in both mass and power because spacecraft have to travel over a billion miles to get there and require a large amount of fuel, not only to reach Titan, but to maintain the ability to maneuver when they arrive. Landed missions have additional limitations, in that they must be packaged in a sealed aeroshell for entry into Titan’s atmosphere. Increases in landed mass and volume translate to increased aeroshell mass and size, requiring even more fuel for delivery to Titan. Nevertheless, missions during which such systems and instruments could be employed range from Discovery and New Frontiers class in situ probes that might be launched in the next decade, to a full-up Flagship class mission anticipated to follow the Europa Jupiter System Mission. Capitalizing on recent breakthroughs in cryo-technologies and smart materials fabrication, we developed conceptual designs of sample acquisition systems and instruments capable of in situ operation under low temperature environments. The study included two workshops aimed at brainstorming and actively discussing a broad range of ideas and associated challenges with landing instruments on Titan, as well as more focused discussions during the intervening part of the study period. The workshops each lasted ~4 days (Monday-Thursday/Friday), included postdoctoral fellows and students in addition to the core team members, and generated active engagement from the Caltech and JPL team participants, as well as from the outside institutions. During the workshops, new instruments and sampling methodologies were identified to handle the challenges of characterizing everything from small molecules in Titan’s upper atmosphere to gross mixtures of high molecular weight complex organics in condensed phases, including atmospheric aerosols and “organic sand” in dunes, to highly dilute components in ices and lakes. To enable these advances in cryogenic instrumentation breakthroughs in a wide range of disciplines, including electronics, chemical and mechanical engineering, and materials science were identified

Future Missions to Titan: Scientific and Engineering Challenges

Saturn’s largest moon, Titan, has been an enigma at every stage of its exploration. For three decades after the hazy atmosphere was discovered from the ground in the 1940s, debate ensued over whether it was a thin layer of methane or a dense shield of methane and nitrogen. Voyager 1 settled the matter in favor of the latter in 1980, but the details of the thick atmosphere discovered raised even more intriguing questions about the nature of the hidden surface, and the sources of resupply of methane to the atmosphere. The simplest possibility, that an ocean of methane and its major photochemical product ethane might cover the globe, was cast in doubt by Earth-based radar studies and then eliminated by Hubble Space Telescope and adaptive optics imaging in the near-infrared from large ground-based telescopes in the 1990s. These data, however, did not reveal the complexity of the surface that Cassini-Huygens would uncover beginning in 2004. A hydrological cycle appears to exist in which methane (in concert with ethane in some processes) plays the role on Titan that water plays on Earth. Channels likely carved by liquid methane and/or ethane, lakes and seas of these materials—some rivaling or exceeding North America’s Great Lakes in size—vast equatorial dune fields of complex organics made high in the atmosphere and shaped by wind, and intriguing hints of geologic activity suggest a world with a balance of geologic and atmospheric processes that is the solar system’s best analogue to Earth. Deep underneath Titan’s dense atmosphere and active, diverse surface is an interior ocean discovered by Cassini and thought to be largely composed of liquid water. Cassini-Huygens has provided spectacular data and has enabled us to glimpse the mysterious surface of Titan. However the mission will leave us with many questions that require future missions to answer. These include determining the composition of the surface and the geographic distribution of various organic constituents. Key questions remain about the ages of surface features, specifically whether cryovolcanism and tectonism are actively ongoing or are relics of a more active past. Ammonia, circumstantially suggested to be present by a variety of different kinds of Cassini-Huygens data, has yet to be seen. Is methane out-gassing from the interior or ice crust today? Are the lakes fed primarily by rain or underground methane-ethane aquifers (more properly, “alkanofers”) and how often have heavy methane rains come to the equatorial region? We should investigate whether Titan’s surface supported vaster seas of methane in the past, and whether complex self-organizing chemical systems have come and gone in the water volcanism, or even exist in exotic form today in the high latitude lakes. The presence of a magnetic field has yet to be established. A large altitude range in the atmosphere, from 400–900 km in altitude, will remain poorly explored after Cassini. Much remains to be understood about seasonal changes of the atmosphere at all levels, and the long-term escape of constituents to space. Other than Earth, Titan is the only world in our solar system known to have standing liquids and an active “hydrologic cycle” with clouds, rains, lakes and streams. The dense atmosphere and liquid lakes on Titan’s surface can be explored with airborne platforms and landed probes, but the key aspect ensuring the success of future investigations is the conceptualization and design of instruments that are small enough to fit on the landed probes and airborne platforms, yet sophisticated enough to conduct the kinds of detailed chemical (including isotopic), physical, and structural analyses needed to investigate the history and cycling of the organic materials. In addition, they must be capable of operating at cryogenic temperatures while maintaining the integrity of the sample throughout the analytic process. Illuminating accurate chemistries also requires that the instruments and tools are not simultaneously biasing the measurements due to localized temperature increases. While the requirements for these techniques are well understood, their implementation in an extremely low temperature environment with limited mass, power and volume is acutely challenging. No such instrument systems exist today. Missions to Titan are severely limited in both mass and power because spacecraft have to travel over a billion miles to get there and require a large amount of fuel, not only to reach Titan, but to maintain the ability to maneuver when they arrive. Landed missions have additional limitations, in that they must be packaged in a sealed aeroshell for entry into Titan’s atmosphere. Increases in landed mass and volume translate to increased aeroshell mass and size, requiring even more fuel for delivery to Titan. Nevertheless, missions during which such systems and instruments could be employed range from Discovery and New Frontiers class in situ probes that might be launched in the next decade, to a full-up Flagship class mission anticipated to follow the Europa Jupiter System Mission. Capitalizing on recent breakthroughs in cryo-technologies and smart materials fabrication, we developed conceptual designs of sample acquisition systems and instruments capable of in situ operation under low temperature environments. The study included two workshops aimed at brainstorming and actively discussing a broad range of ideas and associated challenges with landing instruments on Titan, as well as more focused discussions during the intervening part of the study period. The workshops each lasted ~4 days (Monday-Thursday/Friday), included postdoctoral fellows and students in addition to the core team members, and generated active engagement from the Caltech and JPL team participants, as well as from the outside institutions. During the workshops, new instruments and sampling methodologies were identified to handle the challenges of characterizing everything from small molecules in Titan’s upper atmosphere to gross mixtures of high molecular weight complex organics in condensed phases, including atmospheric aerosols and “organic sand” in dunes, to highly dilute components in ices and lakes. To enable these advances in cryogenic instrumentation breakthroughs in a wide range of disciplines, including electronics, chemical and mechanical engineering, and materials science were identified

Techno–ecological synergies of solar energy for global sustainability

The strategic engineering of solar energy technologies—from individual rooftop modules to large solar energy power plants—can confer significant synergistic outcomes across industrial and ecological boundaries. Here, we propose techno–ecological synergy (TES), a framework for engineering mutually beneficial relationships between technological and ecological systems, as an approach to augment the sustainability of solar energy across a diverse suite of recipient environments, including land, food, water, and built-up systems. We provide a conceptual model and framework to describe 16 TESs of solar energy and characterize 20 potential techno–ecological synergistic outcomes of their use. For each solar energy TES, we also introduce metrics and illustrative assessments to demonstrate techno–ecological potential across multiple dimensions. The numerous applications of TES to solar energy technologies are unique among energy systems and represent a powerful frontier in sustainable engineering to minimize unintended consequences on nature associated with a rapid energy transition

Study protocol for a randomized trial of a supportive care mobile application to improve symptoms, coping, and quality of life in patients with advanced non-small cell lung cancer

Patients with advanced non-small cell lung cancer (NSCLC) often experience burdensome symptoms, emotional distress, and poor quality of life (QOL). While national guidelines recommend early palliative care to address these supportive care needs, most patients with advanced NSCLC lack access to such comprehensive care. Our aim in the current study is to test a novel model of palliative care delivery and use of innovative technology to evaluate the feasibility, acceptability, and preliminary efficacy of a supportive care mobile application (app) for improving symptom management and adaptive coping in patients with advanced NSCLC. We will enroll 120 patients with unresectable Stage III or IV NSCLC diagnosed within the past 12 weeks receiving care with palliative intent at a major academic comprehensive cancer center and its community affiliates. The study will take place in two phases, the first of which will be dedicated to adapting an evidence-based, early palliative care treatment guide and prior supportive care mobile app intervention to address the specific symptom management and coping needs of patients with advanced NSCLC. The second phase of the study will be a two-group, randomized controlled trial. Study patients will complete baseline self-report measures of symptoms, mood, coping skills, and QOL, after which they will be randomized to receive either the mobile app intervention combined with usual oncology care or usual oncology care alone. Intervention patients will use a tablet computer to self-administer the mobile app, which consists of six modules that teach evidence-based skills for managing burdensome symptoms and coping effectively with advanced cancer and its treatment. At 12 weeks follow up, patients in both groups will repeat the same self-report measures. We will use descriptive statistics to determine feasibility metrics of enrollment and retention rates. For secondary self-report measures, we will use linear regression controlling for baseline values. The results of the present study will contribute to a growing body of evidence regarding the supportive care needs of patients with advanced cancer and will have implications for how best to use innovative technology to widely disseminate comprehensive supportive care services to all patients who may benefit.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier[NCT04629300]

Optical Propagation and Communication

Contains an introduction and reports on three research projects.Maryland Procurement Office Contract MDA 903-94-C6071Maryland Procurement Office Contract MDA 904-93-C4169U.S. Air Force - Office of Scientific Research Grant F49620-93-1-0604U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0028U.S. Army Research Office Grant DAAH04-95-1-0494U.S. Air Force - Office of Scientific Research Grant F49620-95-1-0505U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0126U.S. Army Research Office Grant DAAH04-93-G-0399U.S. Army Research Office Grant DAAH04-93-G-018

Do We Practice What We Preach? A Review of Actual Clinical Practice with Regards to Preconception Care Guidelines

Objectives: To review what past studies have found with regard to existing clinical practices and approaches to providing preconception care. Methods: A literature review between 1966 and September 2005 was performed using Medline. Key words included preconception care, preconception counseling, preconception surveys, practice patterns, pregnancy outcomes, prepregnancy planning, and prepregnancy surveys. Results: There are no current national recommendations that fully address preconception care; as a result, there is wide variability in what is provided clinically under the rubric of preconception care. Conclusions: In 2005, the Centers for Disease Control and Prevention sponsored a national summit regarding preconception care and efforts are underway to develop a uniform set of national recommendations and guidelines for preconception care. Understanding how preconception care is presently incorporated and manifested in current medical practices should help in the development of these national guidelines. Knowing where, how, and why some specific preconception recommendations have been successfully adopted and translated into clinical practice, as well as barriers to implementation of other recommendations or guidelines, is vitally important in developing an overarching set of national guidelines. Ultimately, the success of these recommendations rests on their ability to influence and shape women's health policy

The MDT-15 Subunit of Mediator Interacts with Dietary Restriction to Modulate Longevity and Fluoranthene Toxicity in Caenorhabditis elegans

Dietary restriction (DR), the limitation of calorie intake while maintaining proper nutrition, has been found to extend life span and delay the onset of age-associated disease in a wide range of species. Previous studies have suggested that DR can reduce the lethality of environmental toxins. To further examine the role of DR in toxin response, we measured life spans of the nematode Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon, fluoranthene (FLA). FLA is a direct byproduct of combustion, and is one of U.S. Environmental Protection Agency's sixteen priority environmental toxins. Treatment with 5 µg/ml FLA shortened the life spans of ad libitum fed nematodes, and DR resulted in increased sensitivity to FLA. To determine the role of detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator that regulates genes involved in fatty acid metabolism and detoxification. Mutation of mdt-15 increased the life span of FLA treated animals compared to wild-type animals with no difference observed between DR and ad libitum fed mdt-15 animals. We also examined mutants with altered insulin-IGF-1-like signaling (IIS), which is known to modulate life span and stress resistance in C. elegans independently of DR. Mutation of the genes coding for the insulin-like receptor DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals' susceptibility to FLA compared to wild type. Taken together, our results suggest that certain compounds have increased toxicity when combined with a DR regimen through increased metabolic activation. This increased metabolic activation appears to be mediated through the MDT-15 transcription factor and is independent of the IIS pathway

An inhibitor of oxidative phosphorylation exploits cancer vulnerability.

Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors

Food allergy knowledge, attitudes and beliefs: Focus groups of parents, physicians and the general public

<p>Abstract</p> <p>Background</p> <p>Food allergy prevalence is increasing in US children. Presently, the primary means of preventing potentially fatal reactions are avoidance of allergens, prompt recognition of food allergy reactions, and knowledge about food allergy reaction treatments. Focus groups were held as a preliminary step in the development of validated survey instruments to assess food allergy knowledge, attitudes, and beliefs of parents, physicians, and the general public.</p> <p>Methods</p> <p>Eight focus groups were conducted between January and July of 2006 in the Chicago area with parents of children with food allergy (3 groups), physicians (3 groups), and the general public (2 groups). A constant comparative method was used to identify the emerging themes which were then grouped into key domains of food allergy knowledge, attitudes, and beliefs.</p> <p>Results</p> <p>Parents of children with food allergy had solid fundamental knowledge but had concerns about primary care physicians' knowledge of food allergy, diagnostic approaches, and treatment practices. The considerable impact of children's food allergies on familial quality of life was articulated. Physicians had good basic knowledge of food allergy but differed in their approach to diagnosis and advice about starting solids and breastfeeding. The general public had wide variation in knowledge about food allergy with many misconceptions of key concepts related to prevalence, definition, and triggers of food allergy.</p> <p>Conclusion</p> <p>Appreciable food allergy knowledge gaps exist, especially among physicians and the general public. The quality of life for children with food allergy and their families is significantly affected.</p

Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans

Background: Dietary restriction (DR) increases life span and delays age-associated disease in many organisms. The mechanism by which DR enhances longevity is not well understood. Results: Using bacterial food deprivation as a means of DR in C. elegans, we show that transient DR confers long-term benefits including stress resistance and increased longevity. Consistent with studies in the fruit fly and in mice, we demonstrate that DR also enhances survival when initiated late in life. DR by bacterial food deprivation significantly increases life span in worms when initiated as late as 24 days of adulthood, an age at which greater than 50% of the cohort have died. These survival benefits are, at least partially, independent of food consumption, as control fed animals are no longer consuming bacterial food at this advanced age. Animals separated from the bacterial lawn by a barrier of solid agar have a life span intermediate between control fed and food restricted animals. Thus, we find that life span extension from bacterial deprivation can be partially suppressed by a diffusible component of the bacterial food source, suggesting a calorie-independent mechanism for life span extension by dietary restriction. Conclusion: Based on these findings, we propose that dietary restriction by bacterial deprivation increases longevity in C. elegans by a combination of reduced food consumption and decreased food sensing