Correspondence announcing moderator and Faculty Liaison to BALSA

Letter to Dean John F.X. Irving to confirm that Professor William Aldridge is acting in the capacity of Moderator and Faculty liaison to BALSA

Technology Directions for the 21st Century

New technologies will unleash the huge capacity of fiber-optic cable to meet growing demands for bandwidth. Companies will continue to replace private networks with public network bandwidth-on-demand. Although asynchronous transfer mode (ATM) is the transmission technology favored by many, its penetration will be slower than anticipated. Hybrid networks - e.g., a mix of ATM, frame relay, and fast Ethernet - may predominate, both as interim and long-term solutions, based on factors such as availability, interoperability, and cost. Telecommunications equipment and services prices will decrease further due to increased supply and more competition. Explosive Internet growth will continue, requiring additional backbone transmission capacity and enhanced protocols, but it is not clear who will fund the upgrade. Within ten years, space-based constellations of satellites in Low Earth orbit (LEO) will serve mobile users employing small, low-power terminals. 'Little LEO's' will provide packet transmission services and geo-position determination. 'Big LEO's' will function as global cellular telephone networks, with some planning to offer video and interactive multimedia services. Geosynchronous satellites also are proposed for mobile voice grade links and high-bandwidth services. NASA may benefit from resulting cost reductions in components, space hardware, launch services, and telecommunications services

Mutations in DNA repair genes are associated with increased neoantigen burden and a distinct immunophenotype in lung squamous cell carcinoma.

Deficiencies in DNA repair pathways, including mismatch repair (MMR), have been linked to higher tumor mutation burden and improved response to immune checkpoint inhibitors. However, the significance of MMR mutations in lung cancer has not been well characterized, and the relevance of other processes, including homologous recombination (HR) and polymerase epsilon (POLE) activity, remains unclear. Here, we analyzed a dataset of lung squamous cell carcinoma samples from The Cancer Genome Atlas. Variants in DNA repair genes were associated with increased tumor mutation and neoantigen burden, which in turn were linked with greater tumor infiltration by activated T cells. The subset of tumors with DNA repair gene variants but without T cell infiltration exhibited upregulation of TGF-β and Wnt pathway genes, and a combined score incorporating these genes and DNA repair status accurately predicted immune cell infiltration. Finally, high neoantigen burden was positively associated with genes related to cytolytic activity and immune checkpoints. These findings provide evidence that DNA repair pathway defects and immunomodulatory genes together lead to specific immunophenotypes in lung squamous cell carcinoma and could potentially serve as biomarkers for immunotherapy

Astro2020 Science White Paper: Triggered High-Priority Observations of Dynamic Solar System Phenomena

Unexpected dynamic phenomena have surprised solar system observers in the past and have led to important discoveries about solar system workings. Observations at the initial stages of these events provide crucial information on the physical processes at work. We advocate for long-term/permanent programs on ground-based and space-based telescopes of all sizes - including Extremely Large Telescopes (ELTs) - to conduct observations of high-priority dynamic phenomena, based on a predefined set of triggering conditions. These programs will ensure that the best initial dataset of the triggering event are taken; separate additional observing programs will be required to study the temporal evolution of these phenomena. While not a comprehensive list, the following are notional examples of phenomena that are rare, that cannot be anticipated, and that provide high-impact advances to our understandings of planetary processes. Examples include: new cryovolcanic eruptions or plumes on ocean worlds; impacts on Jupiter, Saturn, Uranus, or Neptune; extreme eruptions on Io; convective superstorms on Saturn, Uranus, or Neptune; collisions within the asteroid belt or other small-body populations; discovery of an interstellar object passing through our solar system (e.g. 'Oumuamua); and responses of planetary atmospheres to major solar flares or coronal mass ejections.Comment: Astro2020 white pape

Impact of ultrasound on management for dyspnea presentations in a Rwandan emergency department

Background The complexity of diagnosis for critically ill dyspnea presentations in the emergency department remains a challenge. Accurate and rapid recognition of associated life-threatening conditions is paramount for timely treatment. Point-of-care ultrasound (POCUS) has been shown to impact the diagnosis of dyspnea presentations in resource-rich settings, and may be of greater diagnostic benefit in resource-limited settings. Methods We prospectively enrolled a convenience sample of 100 patients presenting with dyspnea in the Emergency Department at University Teaching Hospital of Kigali (UTH-K) in Rwanda. After a traditional history and physical exam, the primary treating team listed their 3 main diagnoses and ranked their confidence accuracy in the leading diagnosis on a Likert scale (1–5). Multi-organ ultrasound scans performed by a separate physician sonographer assessed the heart, lungs, inferior vena cava, and evaluated for lower extremity deep vein thrombosis or features of disseminated tuberculosis. The sonographer reviewed the findings with the treating team, who then listed 3 diagnoses post-ultrasound and ranked their confidence accuracy in the leading diagnosis on a Likert scale (1–5). The hospital diagnosis at discharge was used as the standard in determining the accuracy of the pre- and post-ultrasound diagnoses. Results Of the 99 patients included in analysis, 57.6% (n = 57) were male, with a mean age of 45 years. Most of them had high-level acuity (54.5%), the dyspnea was of acute onset (45.5%) and they came from district hospitals (50.5%). The most frequent discharge diagnoses were acute decompensated heart failure (ADHF) (26.3%) and pneumonia (21.2%). Ultrasound changed the leading diagnosis in 66% of cases. The diagnostic accuracy for ADHF increased from 53.8 to 100% (p = 0.0004), from 38 to 85.7% for pneumonia (p = 0.0015), from 14.2 to 85.7% for extrapulmonary tuberculosis (p = 0.0075), respectively, pre and post-ultrasound. The overall physician diagnostic accuracy increased from 34.7 to 88.8% pre and post- ultrasound. The clinician confidence in the leading diagnosis changed from a mean of 3.5 to a mean of 4.7 (Likert scale 0–5) (p < 0.001). Conclusions In dyspneic patients presenting to this Emergency Department, ultrasound frequently changed the leading diagnosis, significantly increased clinicians’ confidence in the leading diagnoses, and improved diagnostic accuracy

Influence of the Human Lipidome on Epicardial Fat Volume in Mexican American Individuals

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma lipids on EAT volume. Aim: The focus of this study is on the identification of novel lipidomic species associated with CMRI-derived measures of epicardial fat in Mexican American individuals. Methods: We performed lipidomic profiling on 200 Mexican American individuals. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing measures of 799 unique species from circulating plasma samples. Because of our extended pedigree design, we utilized a standard quantitative genetic linear mixed model analysis to determine whether lipids were correlated with EAT by formally testing for association between each lipid species and the CMRI epicardial fat phenotype. Results: After correction for multiple testing using the FDR approach, we identified 135 lipid species showing significant association with epicardial fat. Of those, 131 lipid species were positively correlated with EAT, where increased circulating lipid levels were correlated with increased epicardial fat. Interestingly, the top 10 lipid species associated with an increased epicardial fat volume were from the deoxyceramide (Cer(m)) and triacylglycerol (TG) families. Deoxyceramides are atypical and neurotoxic sphingolipids. Triacylglycerols are an abundant lipid class and comprise the bulk of storage fat in tissues. Pathologically elevated TG and Cer(m) levels are related to CVD risk and, in our study, to EAT volume. Conclusion: Our results indicate that specific lipid abnormalities such as enriched saturated triacylglycerols and the presence of toxic ceramides Cer(m) in plasma of our individuals could precede CVD with increased EAT volume

Suppression of the intrinsic apoptosis pathway by sinaptic activity

Synaptic activity promotes resistance to diverse apoptotic insults, the mechanism behind which is incompletely understood. We show here that a coordinated downregulation of core components of the intrinsic apoptosis pathway by neuronal activity forms a key part of the underlying mechanism. Activity-dependent protection against apoptotic insults is associated with inhibition of cytochrome c release in most but not all neurons, indicative of anti-apoptotic signaling both upstream and downstream of this step. We find that enhanced firing activity suppresses expression of the proapoptotic BH3-only member gene Puma in a NMDA receptor-dependent, p53-independent manner. Puma expression is sufficient to induce cytochrome c loss and neuronal apoptosis. Puma deficiency protects neurons against apoptosis and also occludes the protective effect of synaptic activity, while blockade of physiological NMDA receptor activity in the developing mouse brain induces neuronal apoptosis that is preceded by upregulation of Puma. However, enhanced activity can also confer resistance to Puma-induced apoptosis, acting downstream of cytochrome c release. This mechanism is mediated by transcriptional suppression of apoptosome components Apaf-1 and procaspase-9, and limiting caspase-9 activity, since overexpression of procaspase-9 accelerates the rate of apoptosis in active neurons back to control levels. Synaptic activity does not exert further significant anti-apoptotic effects downstream of caspase-9 activation, since an inducible form of caspase-9 overrides the protective effect of synaptic activity, despite activity-induced transcriptional suppression of caspase-3. Thus, suppression of apoptotic gene expression may synergize with other activity-dependent events such as enhancement of antioxidant defenses to promote neuronal survival

Results from the CERN pilot CLOUD experiment

During a 4-week run in October–November 2006, a pilot experiment was performed at the CERN Proton Synchrotron in preparation for the Cosmics Leaving OUtdoor Droplets (CLOUD) experiment, whose aim is to study the possible influence of cosmic rays on clouds. The purpose of the pilot experiment was firstly to carry out exploratory measurements of the effect of ionising particle radiation on aerosol formation from trace H2SO4 vapour and secondly to provide technical input for the CLOUD design. A total of 44 nucleation bursts were produced and recorded, with formation rates of particles above the 3 nm detection threshold of between 0.1 and 100 cm -3 s -1, and growth rates between 2 and 37 nm h -1. The corresponding H2O concentrations were typically around 106 cm -3 or less. The experimentally-measured formation rates and htwosofour concentrations are comparable to those found in the atmosphere, supporting the idea that sulphuric acid is involved in the nucleation of atmospheric aerosols. However, sulphuric acid alone is not able to explain the observed rapid growth rates, which suggests the presence of additional trace vapours in the aerosol chamber, whose identity is unknown. By analysing the charged fraction, a few of the aerosol bursts appear to have a contribution from ion-induced nucleation and ion-ion recombination to form neutral clusters. Some indications were also found for the accelerator beam timing and intensity to influence the aerosol particle formation rate at the highest experimental SO2 concentrations of 6 ppb, although none was found at lower concentrations. Overall, the exploratory measurements provide suggestive evidence for ion-induced nucleation or ion-ion recombination as sources of aerosol particles. However in order to quantify the conditions under which ion processes become significant, improvements are needed in controlling the experimental variables and in the reproducibility of the experiments. Finally, concerning technical aspects, the most important lessons for the CLOUD design include the stringent requirement of internal cleanliness of the aerosol chamber, as well as maintenance of extremely stable temperatures (variations below 0.1 °C