cssi/SciSciGPT-SciSciNet huggingface dataset:
Multivalent Ligand-Receptor Binding on Supported Lipid Bilayers

Abstract Fluid supported lipid bilayers provide an excellent platform for studying multivalent protein–ligand interactions because the two-dimensional fluidity of the membrane allows for lateral rearrangement of ligands in order to optimize binding. Our laboratory has combined supported lipid bilayer-coated microfluidic platforms with total internal reflection fluorescence microscopy (TIRFM) to obtain equilibrium dissociation constant ( K D ) data for these systems. This high throughput, on-chip approach provides highly accurate thermodynamic information about multivalent binding events while requiring only very small sample volumes. Herein, we review some of the most salient findings from these studies. In particular, increasing ligand density on the membrane surface can provide a modest enhancement or attenuation of ligand–receptor binding depending upon whether the surface ligands interact strongly with each other. Such effects, however, lead to little more than one order of magnitude change in the apparent K D values. On the other hand, the lipophilicity and presentation of lipid bilayer-conjugated ligands can have a much greater impact. Indeed, changing the way a particular ligand is conjugated to the membrane can alter the apparent K D value by at least three orders of magnitude. Such a result speaks strongly to the role of ligand availability for multivalent ligand–receptor binding.
Evaluating the consistency of understorey vegetation response to forest thinning through synthetic analysis of operational-scale experiments

Summary We attempted to extend the inference scope of several detailed songbird habitat restoration studies in western Oregon to the broader region through a reanalysis and synthesis of fi ve largescale management experiments. This previous work demonstrated the importance of understorey vegetation to songbird habitat. However, individual studies have shown confl icting results regarding how vegetation responds to restoration thinning. Understorey vegetation covers 4 – 6 years after thinning was strongly related to pre-treatment conditions (indexed by the unthinned control treatment). Baseline models that accounted for the pre-treatment conditions showed that herbaceous cover consistently, but only slightly, increased following thinning. Shrub cover, however, tended to decrease following thinning when the pre-treatment cover was >30 per cent. Each study had limited replication and most had limited geographic and environmental conditions, leading to the inconsistent fi ndings when analysed separately. The reanalysis approach allowed us to test the repeatability of specifi c fi nding and demonstrated the applicability of restoration thinning for enhancing habitat in western Oregon.
Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation.

Background Central pontine myelinolysis (CPM) is the most detrimental neurologic complication after liver transplantation. The incidence of CPM after liver transplantation ascends to 17%. Although the precise etiology and pathogenesis of CPM is largely unknown, a growing literature implicates a possible role of immunosuppressive agents, such as Cyclosporine (incidence 30%) on its development. Other immunosuppressive agents also can cause CPM but the frequency of these cases is less compared to Cyclosporine. There is only one case report for Tacrolimus (FK506)-associated speech disorder, which might be an atypical presentation of CPM, and no case reports for Rapamycin. We present a case of Tacrolimus induced CPM. Case report A 62-year-old woman who underwent liver transplantation developed clinical symptoms with radiologic evidence consistent with CPM 7 days after liver transplant. Since the electrolytes in this patient remained normal from her admission, the hypothesis of inmunossupressor neurotoxicity was established and the therapy was switched, resulting in an evident clinical and radiological improvement of her condition in the following days. Five months later, the patient's only neurological deficit was slight dysarthria and a follow-up MRI showed no abnormalities. Conclusions This case provides evidence of Tacrolimus-associated CPM after transplantation, which presented with a classic "lock-in syndrome" with radiographic confirmation.
Genetic Attributions, Immutability, and Stereotypical Judgments: An Analysis of Homosexuality*

Objectives Individuals employ causal reasoning to explain the world around them, including political events, group behavior, and conditions in society. People may attribute causes of behavior to controllable components, such as individual choices, or uncontrollable elements, such as broader forces in the environment. To this, we add biological or genetic attributions that have received increasing attention. Broadly, we argue that people's understanding about genetics as a cause for group behavior influences perceptions of immutability and stereotypical judgments about groups. Methods Making use of individual-level data from three national surveys of American adults, we examine causal beliefs about the origins of homosexuality. Specifically, we assess the impact of genetic attributions on judgments about whether a gay or lesbian person's sexual orientation can or cannot be changed. We also examine the association between genetic attributions and several stereotypic judgments about gays and lesbians. Results We find that genetic attributions strongly shape perceptions of immutability as well as stereotypic judgments about gays and lesbians. Conclusions Implications of our findings for attribution theory and the attitudinal changes that follow from the public's understanding of genetics and its impact on sexual orientation are discussed.
Glucosamine induces REDD1 to suppress insulin action in retinal Müller cells.

Resistance to insulin action is a key cause of diabetic complications, yet much remains unknown about the molecular mechanisms that contribute to the defect. Glucose-induced insulin resistance in peripheral tissues such as the retina is mediated in part by the hexosamine biosynthetic pathway (HBP). Glucosamine (GAM), a leading dietary supplement marketed to relieve the discomfort of osteoarthritis, is metabolized by the HBP, and in doing so bypasses the rate-limiting enzyme of the pathway. Thus, exogenous GAM consumption potentially exacerbates the resistance to insulin action observed with diabetes-induced hyperglycemia. In the present study, we evaluated the effect of GAM on insulin action in retinal Muller cells in culture. Addition of GAM to Muller cell culture repressed insulin-induced activation of the Akt/mTORC1 signaling pathway. However, the effect was not recapitulated by chemical inhibition to promote protein O-GlcNAcylation, nor was blockade of O-GlcNAcylation sufficient to prevent the effects of GAM. Instead, GAM induced ER stress and subsequent expression of the protein Regulated in DNA Damage and Development (REDD1), which was necessary for GAM to repress insulin-stimulated phosphorylation of Akt on Thr308. Overall, the findings support a model whereby GAM promotes ER stress in retinal Muller cells, resulting in elevated REDD1 expression and thus resistance to insulin action.
Risks of inadequate nutrition in disabled children: four cases of scurvy

Scurvy is the clinical consequence of chronic vitamin C deficiency. It is the oldest known nutritional disease, with the first report being in the 1550 BC Papyrus of Ebers, which includes a clear recommendation to eat some vegetables.1 Today, scurvy is rare and almost exclusively associated with malnutrition, malabsorption or psychiatric disease. Recently, in the paediatric population neurological impairment or autistic spectrum disorders have also emerged as risk factors for scurvy owing to food selectivity leading to a potentially fresh fruit- and vegetable-free diet.2 ,3 In view of these recent observations, we checked our database to evaluate the prevalence of scurvy in a subset of disabled children who are cared for …
Obligations of productive justice: individual or institutional?

If it is a requirement of justice that everyone has access to basic goods and services, then justice requires that the work that is necessary to produce the relevant goods and provide the relevant ...
The Role of Intermolecular Interactions in the Polymerization of Actin by Formins

Formins are large multidomain proteins that nucleate and modulate the elongation of actin filaments. The FH2 domains (∼400 amino acids) remain associated with the growing barbed end and slow elongation by 5 to 95% depending on the particular formin. We use all atom and coarse-grained molecular dynamics simulations to investigate the interactions of three formins FH2 domains (fission yeast Cdc12, budding yeast Bni1p, mouse mDia1) and the barbed end of the actin filament to understand these formins polymerize actin at different rates. The simulations demonstrated that dissimilarities in the structures and intermolecular interactions of three formin-actin complexes, which can affect their elongation rates. In addition, the interactions between FH2 domains and actin filament affect the configuration of the barbed end of the filament, and we identified critical regions of formins that play role in regulating the barbed-end configuration. Our coarse-grained simulations predicted these formins have different degrees of steric interference to the addition of actin monomer to the barbed end, and it was found to be inversely proportional to their rates of polymerization. This work can help to resolve the underlying molecular mechanisms used by different formins to assemble actin networks.
Preserving brain function in a comatose patient with septic hyperpyrexia (41.6 °C): a case report.

Pyrexia is a physiological response through which the immune system responds to infectious processes. Hyperpyrexia is known to be neurodegenerative leading to brain damage. Some of the neurotoxic effects of hyperpyrexia on the brain include seizures, decreased cognitive speed, mental status changes, coma, and even death. In the clinical management of hyperpyrexia, the goal is to treat the underlying cause of elevated temperature and prevent end organ damage. This case illustrates a 39-year-old white American man referred from another medical facility where he had undergone an upper gastrointestinal tract diagnostic procedure which became complicated by blood aspiration and respiratory distress. During hospitalization, he developed a core body temperature of 41.6 °C (106.9 °F) leading to cognitive decline and coma with a Glasgow Coma Score of 3. Levetiracetam and amantadine were utilized effectively for preserving and restoring neurocognitive function. Prior studies have shown that glutamate levels can increase during an infectious process. Glutamate is an excitatory neurotransmitter that is utilized by the organum vasculosum laminae terminalis through the neuronal excitatory system and causes an increase in body temperature which can lead to hyperpyrexia. Similar to neurogenic fevers, hyperpyrexia can lead to neurological decline and irreversible cognitive dysfunction. Inhibition of the glutamate aids a decrease in excitatory states, and improves the brain’s regulatory mechanism, including temperature control. To further improve cognitive function, dopamine levels were increased with a dopamine agonist. We propose that a combination of levetiracetam and amantadine may provide neuroprotective and neurorestorative properties when administered during a period of hyperpyrexia accompanied by any form of mental status changes, particularly if there is a decline in Glasgow Coma Score.
Electronic Structures of Small (RuO2)n (n = 1-4) Nanoclusters and Their Anions and the Hydrolysis Reactions with Water.

Group 8 (RuO2)n (n = 1–4) nanoclusters, their anions, and the hydrolysis reactions of the neutral clusters have been studied with the density functional theory (DFT) as well as coupled cluster CCSD(T) theory. The ground state is predicted to be a singlet and a doublet for the neutral RuO2 clusters and anionic clusters, respectively. The CCSD(T) method is required to predict the correct ground state. The calculated singlet–triplet gaps (<15 kcal/mol) and fluoride affinities (<95 kcal/mol) are smaller than those of the group 4 (MO2)n and group 6 (MO3)n metal oxide clusters. The electron affinities range from 2.2 to 3.4 eV, showing that the RuO2 clusters are quite reducible. Clustering energies and heats of formation are calculated. The water physisorption energies are predicted to be −10 to −20 kcal/mol with the adsorption energy for the singlet being generally more exothermic than that for the triplet. The hydrolysis reactions are exothermic for the monomer and dimer clusters and are slightly endothermic o...
Solar radiation measurements in Algeria: case of Ghardaïa station as member of the enerMENA meteorological network

Abstract A comprehensive knowledge of available solar energy amount in a specific location is crucial for the successful development for solar energy policies and investment. Indeed, PV or CSP systems require reliable information on solar radiation measurements. This could be obtained from solar radiation data measured by meteostations installed in different places of the site under consideration. In this paper, an overview of solar radiation measurements assessment in Ghardaia region has been analysed. The choice of this site is based on its membership to the enerMENA meteorological network. The investigation of the data has exposed a huge solar potential where the average annual global solar radiation received on horizontal surface is about 2149 kWh/m2 and the DNI about of 2305 kWh/m2. The comparison with satellite derived data has provided and error of about 4.67% for the global radiation and 0.25% for DNI solar radiation.
Integers and the Sum of the Factorials of their Digits

(1971). Integers and the Sum of the Factorials of their Digits. Mathematics Magazine: Vol. 44, No. 5, pp. 278-279.
Effects of tidal forcing in an estuarine environment on high-frequency acoustics

Tidal forcing in rivers and estuaries has a large impact on the use high-frequency acoustics for bathymetric mapping. Changes in the sound speed profile due to changing salinity and temperature conditions affect acoustic propagation, and bubbles, entrained in the tidal flow, cause high backscattering and attenuation. In this study, a forward-looking, high-frequency bathymetric sonar was used to observe estuarine dynamics near the mouth of the Connecticut River in June 2017. The sonar was deployed on a REMUS 600 AUV under the fresh water plume near the river mouth during flood tide, in the lower estuary during ebb tide and in the upper estuary during slack tide. Backscattering from subducted bubbles was observed which was dependent on the propagation path through the fresh or salt water. The bubble backscatter over a 200-m swath at the front of the fresh water plume allowed the structure of the plume to be observed from beneath the surface. These data are compared with other measurements on site, including...
Managing domain knowledge and multiple models with boosting

We present MBoost, a novel extension to AdaBoost that extends boosting to use multiple weak learners explicitly, and provides robustness to learning models that overfit or are poorly matched to data. We demonstrate MBoost on a variety of problems and compare it to cross validation for model selection.
Design space exploration and optimization of embedded memory systems

Recent years have witnessed the emergence of microprocessors that are embedded within a plethora of devices used in everyday life. Embedded architectures are customized through a meticulous and time consuming design process to satisfy stringent constraints with respect to performance, area, power, and cost. In embedded systems, the cost of the memory hierarchy limits its ability to play as central a role. This is due to stringent constraints that fundamentally limit the physical size and complexity of the memory system. Ultimately, application developers and system engineers are charged with the heavy burden of reducing the memory requirements of an application. This thesis offers the intriguing possibility that compilers can play a significant role in the automatic design space exploration and optimization of embedded memory systems. This insight is founded upon a new analytical model and novel compiler optimizations that are specifically designed to increase the synergy between the processor and the memory system. The analytical models serve to characterize intrinsic program properties, quantify the impact of compiler optimizations on the memory systems, and provide deep insight into the trade-offs that affect memory system design.
Oligosaccharins ― Plant regulatory molecules

The discoveries that complex carbohydrates are tissue-specific cell-surface antigens and the receptors for hormones, toxins, bacteria, and viruses have created considerable interest in complex carbohydrates. Furthermore, the complex carbohydrate portions of some glycoprotein hormones are required for their biological activity, and the complex carbohydrates of some glycoprotein enzymes keep the enzymes stable, while the carbohydrates of some glycoproteins direct the glycoproteins to their proper locations. Moreover, the immune response to glycoproteins is often directed to their carbohydrate side chains, and the carbohydrate chains have been shown to affect the activity and residence time of glycoprotein pharmaceuticals. Still another discovery that has generated considerable interest in complex carbohydrate research is that these molecules perform regulatory functions in plants and animals, often at the level of controlling gene expression.
Funding for the colleges of medicine: integrated delivery systems to the rescue.

In 1995 colleges of medicine, as part of academic health centers, face major threats of decreases in funding from all their traditional sources. In the past four decades, academic health centers have built themselves into national and regional resources based upon multiple funding streams. The growth in the budgets of their colleges of medicine has been phenomenal, with increases in revenues from $889 million in 1960 to a projected figure of more than $25 billion in 1995 (1). These large revenues are from multiple sources but largely come from research and patient care revenues; however, they are necessary for the survival of the academic health centers as we know them (2-3). Support of undergraduate medical education is only a small part of the overall costs of colleges of medicine. Thus, it is not surprising that only a small fraction of the total college revenues comes from tuition, at both public and private colleges, or subsidies, as is the case with state-supported colleges of medicine (4). However, the true costs of undergraduate medical education are not known, but are now under intense study (5,6). In the past, it has been assumed that much of the educational costs have been borne by a cost shifting (5). In the 1960's and '70's research revenues paid for faculty and resources that provided much of the teaching in colleges of medicine. Numerous rationales were developed to justify this form of cost shifting. In the 1980's and '90's, the funding of faculty and other costs of undergraduate education and unfunded research became more dependent on surplus revenues from clinical care provided by faculty practice plans and with the transfer of revenues from hospitals. Cost shifting of these funds to pay the educational costs has permitted the massive growth of the medical faculty, especially in clinical departments. While research funds have continued to increase, and the NIH expenditures in 1995 will exceed $12 billion, they have not kept pace
Hybrid creature project: groovy graphics assignment

This groovy graphics assignment is actually a multi-staged assignment going from concept through creation to animated presentation of a hybrid creature which could plausibly exist on Earth. Each stage of the project has its own challenges and learning goals and as such, could be broken out to be standalone assignments in their own rights. Some already have been at both the high school and college level. The entire project covers a range of topics including but not limited to comparative anatomy, animal locomotion, animal habitats, food chains, 2D visualization, 3D modeling for animation, digital sculpting, surfacing, lighting, rendering, and animation.
Antimonide Based Infrared Detectors and Focal Plane Arrays

Infrared imaging (3–25μm) has been an important technological tool for the past 60 years since the first report of infrared detectors in 1950s. There has been a dramatic progress in the development of antimonide based detectors and low power electronic devices in the past decade with new materials like InAsSb, InAs/GaSb superlattices and InAs/InAsSb superlattices demonstrating very good performance. One of the unique aspects of the 6.1A family of semiconductors (InAs, GaSb and AlSb) is the ability to engineer the bandstructure to obtain designer band-offsets. Our group recently moved to The Ohio State University where we are setting up new capability for investigation of the antimonide based materials for infrared detectors and focal plane arrays. Our two areas of focus include developing a “materials to manufacturing” capability for realization of these sensors and exploration of novel application for the infrared sensors and imagers. (https://kind.engineering.osu.edu/)
Thematic series on emerging leaders in biological engineering: convergence and new directions.

Over the past two decades, the biological engineering research community has increased its efforts to promote ‘Convergence’. Many research endeavors have thus involved the synergy of multiple perspectives and approaches from originally distinct fields towards driving creative innovative solutions to address many grand challenges that face our society. Here, we introduce the JBE thematic series on emerging leaders in biological engineering. The aim of the series is to disseminate the latest developments in research that integrate the principles of biology and engineering methodologies to address grand challenges in human health and the health of the planet. This thematic series highlights exciting new areas and emerging leaders who are addressing many of these challenges.
In vivo imaging of CSD-induced activation of resident meningeal immune cells: implications for activation of meningeal nociceptors (S47.003)

Objective: To determine the effect of cortical spreading depression (CSD) on the behavior of inflammatory cells in the pia, subarachnoid space, and dura. Background: CSD, the neural correlate of migraine aura, has been shown to cause activation of meningeal nociceptors. To date, little or no information is available regarding the mechanism by which CSD activates the nociceptors. In the current study, we hypothesized that CSD alters the molecular and/or cellular environment in the pia and dura, where the nociceptors exist, to the extent that it is pro-nociceptive. Design/Methods: Using state-of-the-art 2-photon in vivo imaging through the lightly thinned skull, we studied the behavior of meningeal macrophages and dendritic cells before and after initiation of a single wave of CSD. Macrophage behavior was imaged using CX3CR1-GFP mice (labels macrophages in the pia and dura). Dendritic cell behavior was imaged using CD11C-YFP mice (labels dendritic cells). Results: At baseline, meningeal macrophages are not migratory. They display rapidly changing large macropinocytotic or phacgocytic cytoplasmic processes. After CSD, macrophages pull in these processes, adopting a rounder overall shape, which is indicative of activation. This activation was detected in the pia as early as 5 minutes after CSD, but not until 10–20 minutes later in the dura. In contrast, CD11c+ dendritic cells, are highly migratory at baseline but cease migration after CSD – also indicative of activation. Of note, CSD-activated dendritic cells were observed in the pia, but not in the dura. These events can occur adjacent to or in a direct contact with fluorescently labeled dural TRPV1-positive fibers. Conclusions: The findings raise the possibility that activation of immune cells in the pia and dura after CSD may be involved in the activation of meningeal nociceptors, potentially by rendering the environment in which nociceptors reside more inflamed – a condition shown previously as sufficient for activation of nociceptors. Study Supported by: NIH/NINDS grants R37 NS079678, RO1 NS069847, R21 NS085510 Disclosure: Dr. Schain has nothing to disclose. Dr. Melo-Carrillo has nothing to disclose. Dr. Strassman has nothing to disclose. Dr. Burstein has received personal compensation for activities with Allergan, GSK, and Merck as a consultant or member of the scientific advisory board.
Characterizing the sequence and prior chromatin determinants of induced TF binding with bimodal neural networks

Transcription factor (TF) binding specificity is determined via a complex interplay between the TF9s DNA binding preference and cell-type specific chromatin environments. The chromatin features that correlate with TF binding in a given cell-type have been well characterized. For instance, the binding sites for a majority of TFs display concurrent chromatin accessibility. However, concurrent chromatin features reflect the binding activities of the TF itself, and thus provide limited insight into how genome-wide TF binding patterns became established in the first place. To understand the determinants of TF binding specificity, we therefore need to examine how newly activated TFs interact with sequence and preexisting chromatin landscapes to determine their binding sites. Here, we investigate the sequence and preexisting chromatin determinants of TF binding by examining genome-wide binding of TFs that have been induced in well-characterized chromatin environments. We develop a bimodal neural network that jointly models sequence and prior chromatin data to interpret the genome-wide binding patterns of induced TFs. We find that the preexisting chromatin landscape is a differential global determinant of TF binding; incorporating prior chromatin features substantially improves our ability to explain the binding specificity of some TFs, but not others. Furthermore, by analyzing the per-site predictors of TF binding, we show that TF binding in previously inaccessible chromatin tends to correspond to the presence of more favorable cognate DNA sequences. Our model thus provides a framework for modeling, interpreting, and visualizing the joint sequence and chromatin landscapes that determine in vivo TF binding dynamics.
Reply to Marques and Drexler, "Complex Scenario of Homotypic and Heterotypic Zika Virus Immune Enhancement".

We generally agree with the thoughtful assessment of the role of ADE described in the letter of Marques and Drexler (1) and especially with the notion that the balance between ADE and protective immunity is variable across experimental conditions, among individuals, and within individuals over time. …
A Review of Precision Oncology Knowledgebases for Determining the Clinical Actionability of Genetic Variants

The increased availability of tumor genetic testing and targeted cancer therapies contributes to the advancement of precision medicine in the field of oncology. Precision oncology knowledgebases provide a way of organizing clinically relevant genetic information in a way that is easily accessible for both oncologists and patients, facilitating the genetic-based clinical decision making. Many organizations and companies have built precision oncology knowledgebases, intended for multiple users. In general, these knowledgebases offer information on cancer-related genetic variants as well as their associated diagnostic, prognostic, and therapeutic implications, but they often differ in their information curations, designs, and user experiences. It is advisable that oncologists use multiple knowledgebases during their practice to have them complement each other. In the future, convergence towards common standards and formats is needed to ensure that the comprehensive knowledge across all sources can be unified to bring the oncology community closer to the achievement of the goal of precision oncology.
Investigating the Role of Fish and Fishing in Sharing Networks to Build Resilience in Coral Reef Social-Ecological Systems

Social networks have been and remain important in Oceania for building and maintaining social-ecological resilience. However, there is little quantitative information on the role of fish and fishin...
Dear Candidate: Analysts from around the World Offer Personal Reflections on Psychoanalytic Training, Education, and the Profession

In this first-of-kind book, senior psychoanalysts from around the world offer personal reflections on their own training, what it was like to become a psychoanalyst, and what they would like most to convey to the candidate of today. With forty-two personal letters to candidates, this edited collection helps analysts in training and those recently entering the profession to reflect upon what it means to be a psychoanalytic candidate and enter the profession. Letters tackle the anxieties, ambiguities, complications, and pleasures faced in these tasks. From these reflections, the book serves as a guide through this highly personal, complex, and meaningful experience and helps readers consider the many different meanings of being a candidate in a psychanalytic institute. Perfect for candidates and psychoanalytic educators, this book inspires analysts at all levels to think, once again, about this impossible but fascinating profession and to consider their own psychoanalytic development.
Abstract 4471: Patient-reported outcomes and emergency department (ED) visits among gastrointestinal (GI) cancer patients prescribed anti-CTLA4/PD-1/L-1 antibody immunotherapy

Introduction: Leveraging electronic Patient Reported Outcomes (ePRO) improves cancer care delivery by reducing ED visits/hospitalizations and increasing overall survival. Yet little is known patient-reported outcomes or association with ED visits outcomes following immunotherapy. Here, we describe systematic ePRO collection using 15 core symptoms via the validated Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE) tool among pts prescribed anti-CTLA4/PD-1/L-1 antibody immunotherapy for GI cancer. Methods: We previously demonstrated feasibility of an electronic health record (EHR)-embedded ePRO collection via iPads for nearly 70% of new and established patients across Dana-Farber Cancer Institute ambulatory oncology practices. ePRO is deployed once weekly to established patients at home via the EHR patient portal or in clinic via tablet. Patient responses are scored using an algorithm, scaled 0-3, with scores of 3 indicating moderate/severe symptomatic adverse events (SAEs; equivalent to CTCAE grade 3+). We examined pt/disease/immunotherapy treatment characteristics, symptom burden at baseline, SAEs for pts prescribed Pembrolizumab, Nivolumab, Atezolizumab, Ipilimumab, Durvalumab, or Avelumab between January 2018 - August 2019. Exploratory analysis include frequency of ED visits at 30/60/90/120 days from immunotherapy start among subset reporting moderate/severe SAEs. Findings: Fifty-one (12.98%) of the 393 eligible pts prescribed immunotherapy used ePRO to report SAEs with median followup of 105 days (interquartile range 43-189). The summary distribution of SAEs across 15 PRO-CTCAE domains shows that moderate/severe SAEs reported were fatigue (19.61%), insomnia (11.76%), and general pain (21.57%); least frequently reported SAEs were fever/rash/vomiting (0%), and nausea (1.96%). In exploratory analysis, 111 (28%) patients had an ED visit, 37(9.40%) occurred within the first 90 days of treatment. Conclusions: We demonstrate proof-of-principle that ePRO implementation in routine practice is feasible, describes the distribution of patient-reported SAEs, and can be evaluated relative to key clinical outcomes such as ED utilization following immunotherapy. Further analysis will examine pt/disease/treatment characteristics predicting moderate/severe SAEs and inferior clinical outcomes. With increased response rates, we will leverage ePRO to develop targeted population health management interventions for patients prescribed immunotherapy in ambulatory oncology practice. Citation Format: Nadine J. McCleary, Jessica Cleveland, Sunyi Zhang, Vivek Upadhyay, Michael Hassett. Patient-reported outcomes and emergency department (ED) visits among gastrointestinal (GI) cancer patients prescribed anti-CTLA4/PD-1/L-1 antibody immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4471.
Thermobarometry of CO2-rich, silica-undersaturated melts constrains cratonic lithosphere thinning through time in areas of kimberlitic magmatism

Abstract Cratonic lithosphere is believed to have been chemically buoyant and mechanically resistant to destruction over billions of years. Yet the absence of cratonic roots at some Archean terrains casts doubt on the craton stability and longevity on a global scale. As unique mantle-derived melts at ancient continents, silica-poor, kimberlitic melts are ideal tools to constrain the temporal variation of lithosphere thickness and the processes affecting the lithosphere root. However, no reliable thermobarometer exists to date for strongly silica-undersaturated, mantle-derived melts. Here we develop a new thermobarometer for silica-poor, CO2-rich melts using high-temperature, high-pressure experimental data. Our barometer is calibrated based on a new observation of pressure-dependent variation of Al2O3 in partial melts saturated with garnet and olivine, while our thermometer is calibrated based on the well-known olivine-melt Mg-exchange. For applications to natural magmas, we also establish a correction scheme to estimate their primary melt compositions. Applying this liquid-based thermobarometer to the estimated primary melt compositions for a global kimberlite dataset, we show that the equilibration depths between primary kimberlite melts and mantle peridotites indicate a decrease of up to ∼150 km in cratonic lithosphere thickness globally during the past ∼2 Gyr. Together with the temporal coupling between global kimberlite frequency and cold subduction flux since ∼2 Gyr ago, our results imply a causal link between lithosphere thinning and supply of CO2-rich melts enhanced by deep subduction of carbonated oceanic crusts. While hibernating at the lithosphere root, these melts chemically metasomatize and rheologically weaken the rigid lithosphere and consequently facilitate destruction through convective removal in the ambient mantle or thermo-magmatic erosion during mantle plume activities.
Why is Diuresis-related Weight Loss Not a Consistent Predictor of Clinical Outcomes in Heart Failure? -need to Account For Variability in Volume Status

Introduction Change in body weight is a common metric used to assess adequacy of decongestive therapy in patients hospitalized for heart failure (HF). However, the findings of clinical studies linking this metric to clinical decongestion and outcomes are mixed. We propose this reflects the failure to take into account biologic variability in intravascular volume status which would impact response to therapy. Methods Data were prospectively collected in hospitalized patients requiring diuresis. Plasma volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by median diuresis-related weight loss and analyzed for 1-year outcome of HF-related mortality or 1st re-hospitalization, and the relation of change in weight to change in PV admission to discharge. Results The cohort was composed of 138 patients with median weight loss of 6 (IQR -3.2, -8.1) kg during hospitalization (5 IQR 4, 6 days). Greater than median weight loss (Figure 1) did not result in better outcomes. At the time of hospital discharge the subgroup with greater weight loss (N=61) paradoxically demonstrated greater absolute (4.8±1.0 vs. 4.2±1.0 liters, p Conclusions Diuresis-related changes in weight reflect clinical decongestion but do not consistently reflect better HF outcomes and, importantly, do not accurately reflect changes in intravascular volume. A basis for this discordance is the significant patient-to-patient variability in volume both at admission and discharge which confounds interpretation of surrogate metrics of decongestion. Failure to account for the marked heterogeneity in volume status contributes to the observed discordance between metrics of clinical decongestion and HF outcomes.
Putting the Virome on the Map: The Influence of Host Geography and Ethnicity on the Gut Virome.

We know little about factors that ordain the composition of the diverse community of viruses (virome) in the human gut. In this issue of Cell Host & Microbe, Zuo et al. highlight the importance of geography, urbanization, ethnicity, and diet on the shape of the adult gut DNA virome.
Schistosoma mansoni infection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome

Despite strong evidence that helminth infections are protective against the development of metabolic disease, a major gap exists in understanding the mechanism(s) underlying this. We have previously found that Schistosoma mansoni induces profound alterations to the metabolic transcriptome of hepatic macrophages and protects male ApoE -/- on high fat diet from the development of obesity, glucose intolerance, and atherosclerosis. Here we demonstrate that macrophages derived from the bone marrow (BMDM) of S. mansoni infected male ApoE -/- mice have dramatically increased mitochondrial respiration and mitochondrial mass compared to those from uninfected mice. This change is accompanied by increased glucose and palmitate shuttling into TCA cycle intermediates and decreased accumulation of cellular cholesterol esters. The systemic effects of metabolic modulation by schistosome infection are a function of biological sex, where schistosome infection protects ApoE -/- male mice from obesity, glucose intolerance, and increased serum triglycerides, but not female mice. The sex-dependent effects of infection extend to myeloid cells specifically, where metabolic reprogramming leads to opposite cholesterol phenotypes in BMDM from infected females and males. Finally, we demonstrate that the metabolic reprogramming of male myeloid cells is transferrable via bone marrow transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of ongoing schistosome antigen exposure. This work provides strong evidence that S. mansoni systemically reprograms the metabolism of the myeloid compartment in a sex-dependent manner.
Spare Strategy Analysis for Life Support Systems for Human Space Exploration

Systems enabling long-duration crewed missions are expected to have high probabilities of success through sparing of components. To enable such systems, the tradeoff between reliability and mass ne...
What About Promotores? Promotores' Psychosocial Determinants That Influenced the Delivery of a Cervical Cancer Education Intervention to Hispanics

This study tested whether a cancer education intervention affected promotores' self-efficacy to deliver an intervention to Hispanics and which psychosocial determinants of promotores influenced the number of Hispanic residents reached by promotores in the subsequent education intervention. A quasi-experimental, pre/post-design with a treatment group (no control) assessed differences for promotores (n = 136) before and after exposure to the cancer education intervention. The design also included a cross-sectional evaluation of the number of residents promotores reached with the educational intervention. After being trained, the promotores delivered the intervention to Hispanic residents (n = 1,469). Paired t-tests demonstrated increases in promotores' self-efficacy from pre- to post-intervention. Regression models assessed associations between the numbers of residents reached and select psychosocial determinants of promotores. Age and promotores' years of experience influenced their delivery of a cervical cancer education intervention to Hispanics, but not their delivery of breast or colorectal cancer education interventions. This is the first study to examine which psychosocial determinants influence promotores delivery of cancer education interventions. The outcomes potentially have implications for CHW interventions and training by examining this potential connection between CHWs' psychosocial determinants and intervention outcomes.
Extending ATM Networks for Efficient Reliable Multicast

One of the important features of ATM networks is their ability to support multicast communication. This facilitates the efficient distribution of multimedia information streams (such as audio and video) to large groups of receivers. Because ATM networks do not provide reliable delivery mechanisms, it is up to end systems to provide end-to-end reliability where it is needed. While this is straightforward for point-to-point virtual circuits, it is more difficult for multicast virtual circuits. This paper proposes extensions to the hardware of ATM switches that enables end systems to implement reliable multicast in a more efficient and scalable manner than is otherwise possible. We essentially provide a network assist to enable end systems to implement reliable multicast more effectively. With our approach, the amount of work that must be done by any receiver in a reliable multicast is independent of the number of participants in the multicast and the amount of work that must be done per packet transmission by any sender, is independent of the number of participants in the multicast. Of course, in large multicasts, a given packet may have to be transmitted multiple times and the number of such transmissions does depend on the number of participants. However, one can show that even under very conservative assumptions this effect does not limit scalability to any significant extent. The proposed reliable multicast mechanisms are being implemented in a scalable ATM switch support 2.4 Gb/s transmission links.
cAMP and tumor necrosis factor competitively regulate transcriptional activation through and nuclear factor binding to the cAMP-responsive element/activating transcription factor element of the endothelial leukocyte adhesion molecule-1 (E-selectin) promoter

Abstract The cAMP-responsive element/activating transcription factor (CRE/ATF) element (also known as NF-ELAM1) of the endothelial leukocyte adhesion molecule-1 (ELAM-1) promoter is necessary for full cytokine responsiveness. It differs from a consensus cAMP-responsive element (CRE) by 1 nucleotide (G-->A conversion) and does not mediate transcriptional activation in response to cAMP. We reported previously that cAMP actually decreases ELAM-1 synthesis induced by tumor necrosis factor (TNF). We now show that cAMP decreases the ELAM-1 promoter response to TNF in transient transfection assays in bovine aortic endothelial cells and that cAMP-mediated inhibition maps to the CRE/ATF element. Electrophoretic mobility shift assays using the ELAM-1 CRE/ATF DNA sequence reveal three complexes. Antibody supershift assays suggest the slowest migrating form (complex 1) contains ATF2, the middle form (complex 2) contains ATF2 and c-Jun, and the fastest migrating form (complex 3) contains a CRE-binding protein. TNF increases c-Jun-containing complex 2 while diminishing complex 1, whereas cAMP decreases complex 2 and increases complex 1. Complex 3 is unchanged by either treatment, and the CRE-binding protein is not phosphorylated. Our data suggest that a change in the composition of the proteins binding to the CRE/ATF promoter element contributes to the competing effects of TNF and cAMP on ELAM-1 gene expression.
Belief Revision in a Deductively Open Belief Space

I am researching the traditional belief revision integrity constraints and postulates, which are designed for deductively closed belief spaces, and revising them so that they are applicable to implemented knowledge representation and reasoning systems with deductively open belief spaces (DOBS). A knowledge representation and reasoning system must be able to deal with contradictions and revise beliefs. This is especially important to data fusion, where information is combined from multiple sources, which might contradict each other. Most theoretical postulates for belief revision and belief contraction assume a deductively closed belief space (DCBS), where all beliefs derivable from a belief space are in that belief space. This is hard (or impossible) to produce in an implemented belief revision system, which has real-world limitations on computation time and database size. This makes it difficult to evaluate such a system using the theoretical postulates; yet evaluating system adherence to these postulates is a pressing issue for those doing belief revision research in computer science. Unlike a DCBS, a DOBS uses a base set of assertions (hypotheses), but only deduces beliefs from that base gradually over time – i.e. some implicit beliefs may not yet be explicit (or part of the belief space). Thus, it can grow even if the base remains static, and it can never be referred to as consistent – only either inconsistent or "not known to be inconsistent." My research begins with a formalism that describes a DOBS and its integrity constraints (ICs) and postulates, which will guide belief revision techniques for implemented systems. This formalism can then be used to better enable system/postulate comparisons. I plan to offer a DOBS version of the AGM postulates (Alchourron, Gardenfors, and Makinson 1985), Hansson’s base contraction postulates (Hansson 1993), and postulates proposed for ranked beliefs, and to provide brief comments regarding postulate adherence for paraconsistent logics and incomplete systems. Using these postulates, I hope to develop a theory for comparing systems, so that implementers will be able to (a) evaluate how well their systems meet the standards of the postulates and (b) compare their systems to other systems.
A BiCMOS universal membership function circuit with fully independent, adjustable parameters

A novel BiCMOS membership function circuit is presented. It implements trapezoidal/triangle functions with all parameters (slope, position, width, height and amplitude) independently and continuously adjustable. Computer simulations are shown that verify the characteristics of the circuit.
Psychiatry and Race

Understanding racial/ethnic differences in psychiatric disorders and treatment requires a multidimensional approach. Research has focused on racial/ethnic differences in the prevalence of psychiatric disorders, in the presentation and meaning of disorders, and in access to and quality of treatment. Racial/ethnic differences are not apparent for all of these dimensions. Keywords: ethnicity; psychiatry; race
YAPPERS: a peer-to-peer lookup service over arbitrary topology

Existing peer-to-peer search networks generally fall into two categories: Gnutella-style systems that use arbitrary topology and rely on controlled flooding for search, and systems that explicitly build an underlying topology to efficiently support a distributed hash table (DHT). In this paper, we propose a hybrid scheme for building a peer-to-peer lookup service over arbitrary network topology. Specifically, for each node in the search network, we build a small DHT consisting of nearby nodes and then provide an intelligent search mechanism that can traverse all the small DHTs. Our hybrid approach can reduce the nodes contacted for a lookup by an order of magnitude compared to Gnutella, allows rapid searching of nearby nodes through quick fan-out, does not reorganize the underlying overlay, and isolates the effect of topology changes to small areas for better scalability and stability.