cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of Insect Development by TGF-β Signaling

Publisher Summary This chapter focuses on the Transforming Growth Factor-beta (TGF-β) system of the well-studied insect Drosophila melanogaster. The TGF-β signaling family uses a relatively simple signal transduction pathway in development of many organisms across the animal kingdom, including insects. The components and functions of both the canonical Bone Morphogenic Protein (BMP) and Activin branches of TGF-β family in Drosophila are discussed, as are instances where the two pathways interact or signal non-canonically. Regulators of the pathway are also presented in several contexts where TGF-β signaling is necessary for proper development. Further the evolution of TGF-β signaling in other insects and arthropods is discussed briefly. TGF-β signaling utilizes extracellular, secreted signaling molecules that bind to receptors on the surface of cells. These receptors then activate a family of proteins inside the cell that ultimately alter transcription of target genes in the nucleus. This general signaling cascade—from outside the cell through the cell membrane and into the nucleus—and the classes of molecules that compose it are strongly conserved throughout the animal kingdom.
Bargaining with Asymmetric Costs for Information

We generalize and correct a model of bargaining with endogenous information acquisition proposed by Dang (2008). Allowing for asymmetric information costs, we show that the opportunity to obtain information during the bargaining process can lead to inefficient outcomes when the responder's cost of obtaining this information is low. We then show that, for very low costs, this inefficiency is robust to allowing agents to voluntarily increase their own information costs and potentially eliminate adverse selection problems.
Consistency and fairness in real-time distributed virtual environments: Paradigms and relationships

Distributed real-time virtual environments entail a well-known set of trade-offs resulting in a lack of state consistency across simulation nodes. This lack of consistency gives rise to a number of challenges that must be addressed by system designers to ensure users remain engaged and satisfied. This paper surveys several approaches to defining, measuring, and controlling the consistency of simulation state data and relates them to the concepts of fairness and fitness for purpose. The interplay between consistency and fairness, in relation to fitness for purpose, must be carefully considered by system engineers to ensure appropriate design trade-offs.
Paravertebral spinal injection for the treatment of patients with degenerative facet osteoarthropathy: Evidence of motor performance improvements based on objective assessments

Abstract Background This study examined short- and long-term improvements in motor performance, quantified using wearable sensors, in response to facet spine injection in degenerative facet osteoarthropathy patients. Methods Adults with confirmed degenerative facet osteoarthropathy were recruited and were treated with medial or intermediate branch block injection. Self-report pain, health condition, and disability (Oswestry), as well as objective motor performance measures (gait, balance, and timed-up-and-go) were obtained in five sessions: pre-surgery (baseline), immediately after the injection, one-month, three-month, and 12-month follow-ups. Baseline motor performance parameters were compared with 10 healthy controls. Findings Thirty patients (age = 50 (14) years) and 10 controls (age = 46 (15) years) were recruited. All motor performance parameters were significantly different between groups. Results showed that average pain and Oswestry scores improved by 51% and 24%, respectively among patients, only one month after injection. Similarly, improvement in motor performance was most noticeable in one-month post-injection measurements; most improvements were observed in gait speed (14% normal walking, P Interpretations Spinal injection can temporarily (one to three months) improve motor performance in degenerative facet osteoarthropathy patients. Successful pain relief in response to treatment is independent of demographic characteristics and initial pain but dependent on baseline motor performance. Immediate self-reported pain relief is unrelated to magnitude of gradual improvement in motor performance.
Potential impacts of the Sunderban mangrove degradation on future coastal flooding in Bangladesh

Abstract The coastal areas of Bangladesh are recognized by the United Nations (UN) as the most vulnerable areas in the world to tropical cyclones and also the sixth most vulnerable country to floods around the world. Cyclone Sidr (2007) was one of the most catastrophic natural disasters in Bangladesh causing nearly 10,000 deaths and $1.7 billion damage. During cyclone Sidr, mangrove forests in coastal areas played a crucial role in the mitigation of these deadly effects. Sunderban mangrove, the world’s largest mangrove ecosystem with 7900 sq. miles, forms the seaward frontier of the bay and is now facing significant degradation. The Sunderban mangrove ecosystem is increasingly being degraded for a variety of purposes such as agriculture, fishing, farming and settlement. In this study, we evaluate the potential impacts from the degradation of the Sunderban mangrove on storm surge flooding. We evaluate two hypothetical and extreme scenarios: 1) the conversion of the entire mangrove land cover to an estuarine forested wetland; and 2) by considering a full degradation scenario where the entire mangrove is converted to grassland. To quantify the benefits of the mangrove forests to attenuate storm surge in this area, we applied a framework combining a spatial characterization of mangroves vegetation with numerical simulations. Storms surge was calculated using a hydrodynamic model (ADCIRC) coupled with wave model (SWAN) under a High Performance Computing environment. An unstructured numerical mesh with 200,000 nodes was developed and validated along with the coupled SWAN + ADCIRC model at six separate locations in the Bangladesh coast using Cyclone Sidr (2007) meteorological inputs. Twenty-seven model simulations were performed considering nine cyclones of different categories to quantify the effects of mangrove degradation on spatial flood inundation and storm surge magnitude. Simulation results showed that, on average, the mangroves degradation to grassland could raise the surge elevation as high as 57% and had a significant impact on increasing the velocity of the flood wave by up to 2730% for category 3 cyclones. In addition, the inundation inland penetration and total flooded area would increase almost 10 km and 18% respectively for low intensity cyclones. Furthermore, these hypothetical scenarios support the importance of the existing Sunderban mangrove in the reduction of surge elevation, velocity, inundation penetration and flooded area. More importantly, it also demonstrates how the continuous degradation of this important ecosystem has the potential to adversely impact the future cyclone induced hazards in the region.
Real-time trip purpose prediction using online location-based search and discovery services

Abstract The use of smartphone technology is increasingly considered a state-of-the-art practice in travel data collection. Researchers have investigated various methods to automatically predict trip characteristics based upon locational and other smartphone sensing data. Of the trip characteristics being studied, trip purpose prediction has received relatively less attention. This research develops trip purpose prediction models based upon online location-based search and discovery services (specifically, Google Places API) and a limited set of trip data that are usually available upon the completion of the trip. The models have the potential to be integrated with smartphone technology to produce real-time trip purpose prediction. We use a recent, large-scale travel behavior survey that is augmented by downloaded Google Places information on each trip destination to develop and validate the models. Two statistical and machine learning prediction approaches are used, including nested logit and random forest methods. Both sets of models show that Google Places information is a useful predictor of trip purpose in situations where activity- and person-related information is uncollectable, missing, or unreliable. Even when activity- and person-related information is available, incorporating Google Places information provides incremental improvements in trip purpose prediction.
Translational Research: Preclinical to Healthy Volunteer to Patient

The development of medicines involves not only the translation of information collected in preclinical in vitro and in vivo experiments to clinical studies in healthy volunteers, also known as T1 translation, but additionally the optimization of the new medication within the environment of medical care, the translation from healthy volunteer to patient, also known as T2 translation. How do the pharmacokinetic parameters vary with different doses? What is the best dose? Can the new medication be combined with other therapies? This chapter begins with a discussion of the overall strategy and individual steps to determine a drug candidate’s pharmacology, absorption, distribution, metabolism, and elimination (ADME), and drug-drug interactions in clinical studies, as well as subsequent evaluation of preclinical predictions. Integration of concentration-time data to develop population pharmacokinetic models and the use of biomarkers in clinical studies are discussed. Biomarkers can be particularly helpful in diseases where obvious clinical pathology may lag behind changes in laboratory values or other more easily measured surrogates. Case studies are also presented illustrating applications of translational research in the development of possible therapeutic agents for the treatment of osteoporosis and Alzheimer’s disease.
A review of sociocultural factors that may underlie differences in African American and European American anxiety

Preliminary evidence indicates there may be differences in the prevalence and severity of anxiety in African Americans and European Americans. A number of sociocultural risk and protective factors have been suggested to contribute to these group differences, such as salience of physical illnesses, discrimination, stigma toward mental illness, religiosity, and ethnic identity. In this paper, the literature concerning each of these factors is reviewed. Overall, the strongest evidence was found for ethnic identity and stigma toward mental illness as factors underlying group differences in anxiety. Ethnic identity and stigma toward mental illness consistently differed by racial group and were associated with anxiety in African Americans. Ethnic identity may buffer against the negative consequences of anxiety, reducing prevalence rates in African Americans. Stigma toward mental illness may decrease African Americans willingness to report anxiety symptoms, reducing overall prevalence rates but increasing the severity of treated cases. The research regarding discrimination, salience of physical illnesses, and religiosity was less clear. Much more research is required, but the findings of this review suggest that future studies should put particular emphasis on stigma toward mental illness and ethnic identity as important factors in understanding African American anxiety outcomes.
Training Surgical Residents With a Haptic Robotic Central Venous Catheterization Simulator.

Ojective Ultrasound guided central venous catheterization (CVC) is a common surgical procedure with complication rates ranging from 5 to 21 percent. Training is typically performed using manikins that do not simulate anatomical variations such as obesity and abnormal vessel positioning. The goal of this study was to develop and validate the effectiveness of a new virtual reality and force haptic based simulation platform for CVC of the right internal jugular vein. Design A CVC simulation platform was developed using a haptic robotic arm, 3D position tracker, and computer visualization. The haptic robotic arm simulated needle insertion force that was based on cadaver experiments. The 3D position tracker was used as a mock ultrasound device with realistic visualization on a computer screen. Upon completion of a practice simulation, performance feedback is given to the user through a graphical user interface including scoring factors based on good CVC practice. The effectiveness of the system was evaluated by training 13 first year surgical residents using the virtual reality haptic based training system over a 3 month period. Results The participants’ performance increased from 52% to 96% on the baseline training scenario, approaching the average score of an expert surgeon: 98%. This also resulted in improvement in positive CVC practices including a 61% decrease between final needle tip position and vein center, a decrease in mean insertion attempts from 1.92 to 1.23, and a 12% increase in time spent aspirating the syringe throughout the procedure. Conclusions A virtual reality haptic robotic simulator for CVC was successfully developed. Surgical residents training on the simulation improved to near expert levels after three robotic training sessions. This suggests that this system could act as an effective training device for CVC.
Automated event detection algorithm for two squatting protocols.

Abstract Introduction Squatting biomechanics assessed using motion analysis relies on the identification of specific events: start of descent, transition between descent/ascent and end of ascent. Automated identification reduces the time needed to process trials while allowing consistency across studies. The purpose of this study was to develop criteria for the identification of events and apply them to two squatting protocols in pathological patient and typically developing (TD) groups. Methods Thirty-four subjects with hip dysplasia and 41 TD subjects were enrolled in this study. While instrumented with a full-body Plug-In-Gait marker set, participants performed two squatting protocols: a hold squat, where subjects paused for a count of three at their lowest squat depth, and a traditional squat, where the descent phase was immediately followed by the ascent phase. Reviewers analyzed the kinematic/kinetic waveforms of a subset of trials to develop criteria for events. Sagittal plane knee and vertical center of mass velocities were used to identify events and absolute vs. relative thresholds of the peak knee velocity were compared. These criteria were incorporated into an automatic event detection code. Results Using a relative threshold algorithm, events were automatically identified in 244 of 259 total trials (94%). For the trials requiring manual placement of events (n = 15 trials), there was perfect inter-rater reliability between research personnel. Conclusions The criteria developed for the automatic detection of squatting events was highly successful for both protocols in each participant group and was also highly reliable for research personnel to follow in the few instances where manual placement was necessary.
Learning to blast a way into crime, or just good clean fun? Examining aggressive play with toy weapons and its relation with crime.

Background Researchers, such as Bandura, have proposed that children's mere exposure to the use of play weapons encourages deviant displays of aggression, but there is very little research to support this hypothesis of 20 years. Aim To examine the relationship between amount of weapon play and concurrent aggression as well as later violent juvenile crime, while controlling for other variables possibly influencing criminal pathways. Method Using longitudinal survey data collected from mothers and children (n = 2019) from age 5, with follow-up at age 15, correlations between children's play with toy weapons and juvenile criminality were examined. Multivariate regression analyses were employed to determine to what extent early childhood aggression, symptoms of attention deficit hyperactivity disorder, and symptoms of depression were antecedents of juvenile crime. Results For bivariate analysis between toy weapon play and juvenile criminality, the effect size was small and not significant. The relationship remained not significant once control variables were introduced into the model. Conclusions and implications The act of pretending to be aggressive in childhood thus plays little role in predicting later criminality after other factors, such as gender, attention deficit hyperactivity disorder or depression, have been taken into account. Involvement in imaginative play with toy gun use in early childhood is unlikely to be useful as a risk marker for later criminal behaviour. Play fighting and war toy games may even be considered necessary components within the frame of normal development. Copyright © 2018 John Wiley & Sons, Ltd.
Modular Ontologies as a Bridge Between Human Conceptualization and Data

Ontologies can be viewed as the middle layer between pure human conceptualization and machine readability. However, they have not lived up to their promises so far. Most ontologies are too tailored to specific data and use-cases. By making sometimes strong, or sometimes too weak, ontological commitments, many existing ontologies do not adequatly reflect human conceptualizations. As a result, sharing and reuse of ontologies is greatly inhibited. In order to more effectively preserve this notion of human conceptualization, an ontology should be designed with modularity and extensibility in mind. A modular ontology thus may act as a bridge between human conceptualization and data.
Place and Policy: Secondhand Smoke Exposure in Bars and Restaurants.

Background Rural populations have been identified as having tobacco use disparities, with contributing factors including less demand for policy change than in urban areas, resulting in higher age-adjusted death rates related to tobacco use. In 2012, the rural state of North Dakota enacted a statewide comprehensive law requiring all bars and restaurants to be smoke-free. Objectives The purpose of this longitudinal study, performed in three phases, was to assess the continued effects of a statewide comprehensive smoke-free law in a primarily rural state, using a stratified random sample. Methods Particulate matter and compliance indicators were assessed in restaurants and bars 21 months after enactment of the comprehensive law. Results were compared with the findings from the Phase 1 and Phase 2 samples, in which venues were assessed before passage of the law and approximately 3 months after enactment, respectively. Results The comprehensive, statewide, smoke-free law led to immediate, sustained, and substantial reductions in secondhand smoke and eliminated previous significant disparities in secondhand smoke exposure in rural communities. Although indoor smoke-free compliance with the law was generally high, compliance in required outdoor smoke-free areas was low. Compliance with signage requirements, both indoors and outdoors, was low. Discussion The comprehensive statewide smoke-free law created a just distribution of smoke-free laws statewide, resulting in increased protection of rural populations from secondhand smoke. Targeted public health interventions to address compliance may reduce secondhand smoke levels in outlier venues that continue to have high levels of secondhand smoke
Review: Regional land subsidence accompanying groundwater extraction

The extraction of groundwater can generate land subsidence by causing the compaction of susceptible aquifer systems, typically unconsolidated alluvial or basin-fill aquifer systems comprising aquifers and aquitards. Various ground-based and remotely sensed methods are used to measure and map subsidence. Many areas of subsidence caused by groundwater pumping have been identified and monitored, and corrective measures to slow or halt subsidence have been devised. Two principal means are used to mitigate subsidence caused by groundwater withdrawal—reduction of groundwater withdrawal, and artificial recharge. Analysis and simulation of aquifer-system compaction follow from the basic relations between head, stress, compressibility, and groundwater flow and are addressed primarily using two approaches—one based on conventional groundwater flow theory and one based on linear poroelasticity theory. Research and development to improve the assessment and analysis of aquifer-system compaction, the accompanying subsidence and potential ground ruptures are needed in the topic areas of the hydromechanical behavior of aquitards, the role of horizontal deformation, the application of differential synthetic aperture radar interferometry, and the regional-scale simulation of coupled groundwater flow and aquifer-system deformation to support resource management and hazard mitigation measures.
Lipid turnover during morphogenesis in the water mold Blastocladiella emersonii

Abstract The lipid content of Blastocladiella emersonii zoospores is 5 pg/cell or about 13% of dry weight. Within the first few minutes of germination 60–70% of total zoospore lipid is lost, with neutral lipid, glycolipid and phospholipid fractions decreasing to about the same extent. These changes in lipid content precede the breakdown during germination of the complex and extensive membrane system of zoospores. During growth, which immediately follows germination, net phospholipid synthesis resumes so that total lipid is maintained at 6% of dry weight, but net synthesis of neutral and glycolipid does not begin until induction of sporulation. During sporulation the phospholipid level decreases so that the distribution of lipid among the three fractions approaches that found in zoospores. These changes in lipid content suggest that zoospore membranes containing neutral and glycolipids are synthesized de novo during spore formation.
Acoustic Measurements of Bubble Densities at 15–50 kHz

Acoustic measurements of near-surface bubbles generated by breaking waves were made off Whidbey Island, Puget Sound, Washington. A limited amount of data was also gathered in the open ocean off the coast of Washington. The intent of these measurements was to delineate the role of near-surface bubbles in surface backscattering, forward loss, and ambient noise at high frequencies. High resolution vertical incidence backscatter was the principal method used for determining the near-surface volume scattering strength profile attributable to bubbles. For one of the data sets low grazing angle forward loss measurements were interspersed with the vertical incidence measurements. It was clear from the vertical incidence measurements that bubbles are acoustically observable at wind speeds as low as 3 m/s and that for wind speeds greater than about 5–6 m/s the surface forward loss can become quite large (>10 dB).
An introduction to lactation and breast-feeding.

An essential characteristic of mammals is the capacity of the female to nourish her offspring with milk, the secretion of the mammary glands. This fluid provides not only nutrients for physical growth but also both immune and nonimmune elements for protection against disease and an opportunity for interaction between newborn and mother which may, at least in higher species of mammals, initiate the learning process necessary to the transition to independent living. In this introductory chapter, we will begin by viewing human lactation from an evolutionary standpoint. Two sections will then be devoted to the historical development of our understanding of milk secretion and its hormonal control. Finally, we will consider breast-feeding in its historical context, a discussion which provides a perspective from which to view the controversy over breast milk versus formula in underdeveloped countries.
A physiochemical processing kinetics model for the vapor phase infiltration of polymers: measuring the energetics of precursor-polymer sorption, diffusion, and reaction

Vapor phase infiltration (VPI) is a new approach for transforming polymers into organic-inorganic hybrid materials with unique properties. Here, we combine experimental measurements with phenomenological theory to develop a universal strategy for measuring, modeling, and predicting the processing kinetics of VPI. We apply our approach to the well-studied VPI system of trimethylaluminum (TMA) infiltrating poly(methyl methacrylate) (PMMA) because the system undergoes both precursor-polymer diffusion and reaction. By experimentally measuring aluminum concentration profiles as a function of film depth with secondary ion mass spectrometry (SIMS) and film swelling with ellipsometry, we have extracted equilibrium solubility and effective diffusivity as a function of process temperature. Fitting these values to appropriate Van't Hoff and Arrhenius relationships, we can then extract enthalpies for precursor sorption and diffusion. We observe an abrupt mechanistic change in both the sorption and diffusion processes around 95 °C, where greater chain mobility at higher processing temperatures lead to greater reactivity between TMA and PMMA. With new understanding of this VPI process, we demonstrate precise control of inorganic infiltration depth and loading fraction into PMMA.
Choreographing the Page

ABSTRACTChoreographing the Page is a visual representation of movement on paper that serves as a hybrid of choreography and an academic reflection writing assignment. It can act as a useful tool to...
The Küme Mongen and the Reign of God

This paper attempts to offer a theological reflection that compares two concepts from two different religious traditions that deal with a similar concern: guiding humanity and the cosmos to flourishing and abundant life. On the one hand, I will consider the Kume Mongen that comes from the Mapuche people of Chile and Argentina. On the other hand, I will consider the concept of the reign of God, so central to the Gospels and re-articulated frequently in Christology, specifically, Latin-American liberation theology. First, I will explain the context from which Kume Mongen emerges and give an account of the central ideas of this concept. Second, I will give an account of the treatment of the reign of God in J.A. Pagola and J. Sobrino’s Christology. Finally, I will explore the possible connections between the Mapuche vision of fruitful life and the Kingdom of God, opening possible paths for mutual learning and understanding between the Mapuche and the Christian religious traditions.
Abelian sandpile model and Biggs–Merino polynomial for directed graphs

Abstract We prove several results concerning a polynomial that arises from the sandpile model on directed graphs; these results are previously only known for undirected graphs. Implicit in the sandpile model is the choice of a sink vertex, and it was conjectured by Perrot and Pham that the polynomial c 0 + c 1 y + … c n y n , where c i is the number of recurrent classes of the sandpile model with level i, is independent of the choice of the sink. We prove their conjecture by expressing the polynomial as an invariant of the sinkless sandpile model. We then present a bijection between arborescences of directed graphs and reverse G-parking functions that preserves external activity by generalizing Cori–Le Borgne bijection for undirected graphs. As an application of this bijection, we extend Merino's Theorem by showing that for any Eulerian directed graph the polynomial c 0 + c 1 y + … c n y n is equal to the greedoid polynomial of the graph.
Genome Sequences of Escherichia Bacteriophages Isolated from Raw Wastewater.

ABSTRACT Somatic coliphages are alternative indicators of fecal pollution and attractive surrogates for viral pathogens. Here, we report the draft genome sequences of three replicate plaques from a novel Myoviridae bacteriophage isolated from raw wastewater. These genomes were similar to felix01virus phage and are predicted to contain up to 148 protein-coding genes.
Mass, Kähler manifolds, and symplectic geometry

In the author’s previous joint work with Hein (Commun Math Phys 347:183–221, 2016), a mass formula for asymptotically locally Euclidean Kahler manifolds was proved, assuming only relatively weak fall-off conditions on the metric. However, the case of real dimension 4 presented technical difficulties that led us to require fall-off conditions in this special dimension that are stronger than the Chruściel fall-off conditions that sufficed in higher dimensions. Nevertheless, the present article shows that techniques of four-dimensional symplectic geometry can be used to obtain all the major results of Hein-LeBrun (2016), assuming only Chruściel-type fall-off. In particular, the present article presents a new proof of our Penrose-type inequality for the mass of an asymptotically Euclidean Kahler manifold that only requires this very weak metric fall-off.
The Confucian Matador: Three Defenses Against the Mechanical Bull

It is critical for designers of language-capable robots to enable some degree of moral competence in those robots. This is especially critical at this point in history due to the current research climate, in which much natural language generation research focuses on language modeling techniques whose general approach may be categorized as "fabrication by imitation" (the titular mechanical "bull"), which is especially unsuitable in robotic contexts. Furthermore, it is critical for robot designers seeking to enable moral competence to consider previously under-explored moral frameworks that place greater emphasis than traditional Western frameworks on care, equality, and social justice, as the current sociopolitical climate has seen a rise of movements such as libertarian capitalism that have undermined those societal goals. In this paper we examine one alternate framework for the design of morally competent robots, Confucian ethics, and explore how designers may use this framework to enable morally sensitive human-robot communication through three distinct perspectives: (1) How should a robot reason? (2) What should a robot say? and (3) How should a robot act?
Elaborating Cancer Opinion Leaders’ Communication Behaviors Within Online Health Communities: Network and Content Analyses:

This study integrates social network and content analyses to examine the communication behaviors of opinion leaders—such as creating threads and engaging in continuous conversations—in two large ca...
CHAPTER 4 – Exercise Metabolism

Publisher Summary This chapter describes energy metabolism during and following exercise, and carbohydrate and fat metabolism during exercise. The energy for muscle contraction arises from the hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate. Aerobic ATP production occurs via oxidative phosphorylation in mitochondria of muscle involving the consumption of oxygen and the production of carbon dioxide and water. Varying proportions of long-chain fatty acids, glycogen, glucose, ketones, and amino acids are oxidized. Long-chain fatty acid oxidation is essential for aerobic production of ATP in working muscle, and utilization arises from lipolysis of intramuscular and extramuscular stores of triglycerides in which one glycerol and three fatty acids are formed as product of a biochemical reaction. A large part of the lactate, which is metabolically removed, involves gluconeogenesis. This process requires energy which ultimately is derived from oxidative metabolism. The lactate threshold in blood signifies when net anaerobic glycolysis begins to contribute significantly to the energetics of exercise in the body as a whole. However, it does not represent the onset of net lactate production in working muscle.
Is robotic surgery feasible at a safety net hospital

Robotic surgery offers potential advantages of improved ability to complete procedures using a minimally invasive approach, recovery, and clinical outcomes. It has been previously established that safety net hospitals are outliers for surgical complications. As such, the adoption of new technology may not achieve the same outcomes as other institutions. We hypothesized that, compared to laparoscopic and open surgeries, robotic surgeries have fewer post-operative Clavien-Dindo complications at our safety net hospital. All robotic surgeries performed from 2017 to 2019 at a single, safety net hospital were reviewed. Cases were matched 1:3 to laparoscopic controls. Surgeries commonly performed open were additionally matched 1:3 to open counterparts. The primary outcome was Clavien-Dindo complications at 90 days post-operatively. Secondary outcomes included inadvertent enterotomy, conversion to open, operative duration, wound class, surgical site infection (SSI), surgical site occurrence (SSO), length of stay (LOS), reoperation, readmission, and recurrence. A total of 160 robotic surgeries were included and matched to 480 laparoscopic surgeries and 108 open surgeries. Open surgeries were associated with greater risk of Clavien-Dindo complication (OR = 2.7, p = 0.040, 95% confidence interval 1.0–6.9) than either robotic or laparoscopic surgeries. Robotic cases had increased operative duration when compared to laparoscopic (p < 0.001) but not open cases (p = 0.093). No difference was seen in enterotomy, conversion to open, SSI, SSO, LOS, reoperation, readmission, or recurrence between robotic and laparoscopic, and robotic and open cases. Robotic surgery is safe and feasible at a safety net hospital. Robotic and laparoscopic surgeries were associated with fewer Clavien-Dindo complications than open surgery, but no differences were seen between robotic and laparoscopic cases. Robotic surgery, compared to both laparoscopic and open surgery, had longer operative durations. Further studies are needed to assess the value of robotic as opposed to laparoscopic surgery in a safety net setting.
Microscopy approaches to study extracellular vesicles

Abstract Background Extracellular vesicles (EVs) have drawn the attention of both biological researchers and clinical physicians due to their function in mediating cell-to-cell communication and relevance as potential diagnostic markers. Since their discovery, the small size and heterogeneity of EVs has posed a hindrance to their characterization as well as to the definition of their biological significance. Scope of the review Recent technological advances have considerably expanded the tools available for EV studies. In particular, the combination of novel microscope setups with high resolution imaging and the flexibility in EV labelling allows for the precise detection and characterization of the molecular composition of single EVs. Here we will review the microscopy techniques that have been applied to unravel the mechanism of EV-mediated intercellular communication and to study their molecular composition. Major conclusions Microscopy technologies have largely contributed to our understanding of molecular processes, including EV biology. As we discuss in this review, careful experimental planning is necessary to identify the most appropriate technique to use to answer a specific question. General significance The considerations regarding microscopy and experimental planning that are discussed here are applicable to the characterization of other small structures, including synthetic nanovectors and viruses.
Brachyury engineers cardiac repair competent stem cells.

To optimize the regenerative proficiency of stem cells, a cardiopoietic protein-based cocktail consisting of multiple growth factors has been developed and advanced into clinical trials for treatment of ischemic heart failure. Streamlining the inductors of cardiopoiesis would address the resource intensive nature of the current stem cell enhancement protocol. To this end, the microencapsulated-modified-mRNA (M3 RNA) technique was here applied to introduce early cardiogenic genes into human adipose-derived mesenchymal stem cells (AMSCs). A single mesodermal transcription factor, Brachyury, was sufficient to trigger high expression of cardiopoietic markers, Nkx2.5 and Mef2c. Engineered cardiopoietic stem cells (eCP) featured a transcriptome profile distinct from pre-engineered AMSCs. In vitro, eCP demonstrated protective antioxidant capacity with enhanced superoxide dismutase expression and activity; a vasculogenic secretome driving angiogenic tube formation; and macrophage polarizing immunomodulatory properties. In vivo, in a murine model of myocardial infarction, intramyocardial delivery of eCP (600 000 cells per heart) improved cardiac performance and protected against decompensated heart failure. Thus, heart repair competent stem cells, armed with antioxidant, vasculogenic, and immunomodulatory traits, are here engineered through a protein-independent single gene manipulation, expanding the available regenerative toolkit.
UNSTABLE DISK ACCRETION ONTO MAGNETIZED STARS : FIRST GLOBAL THREE-DIMENSIONAL MAGNETOHYDRODYNAMIC SIMULATIONS

We report on the first global three-dimensional (3D) MHD simulations of disk accretion onto a rotating magnetized star through the Rayleigh-Taylor instability. The star has a dipole field misaligned relative to the rotation axis by a small angle Θ. Simulations show that, depending on the accretion rate, a star may be in the stable or unstable regime of accretion. In the unstable regime, matter penetrates deep into the magnetosphere through several elongated tongues which deposit matter at random places on the surface of the star, leading to stochastic light curves. In the stable regime, matter accretes in ordered funnel streams and the light curves are almost periodic. A star may switch between these two regimes depending on the accretion rate and may thus show alternate episodes of ordered pulsations and stochastic light curves. In the intermediate regime, both stochastic and ordered pulsations are observed. For -->Θ > 30°, the instability is suppressed and stable accretion through funnel streams dominates.
Healthy Aging Interventions Reduce Repetitive Element Transcripts

Transcripts from noncoding repetitive elements (REs) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze REs in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to a high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that (a) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and high-fat diet (an age-accelerating treatment) increase RE expression; and (b) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Our results suggest that RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.
92418 Molecular imaging of the tumor microenvironment to predict response to combination treatment with immunotherapy in triple negative breast cancer

ABSTRACT IMPACT: Insights from this project will provide clinical guidance in treatment of immunotherapy in triple negative breast cancer and identify early imaging biomarkers of treatment response. OBJECTIVES/GOALS: Significant research that addresses monitoring and predicting patient response of triple negative breast cancer (TNBC) to immunotherapy is needed. Using positron emission tomography (PET) imaging to probe the tumor microenvironment (hypoxia, T-cell activation), we aim to predict early response to immunotherapy for in mouse models of TNBC tumors. METHODS/STUDY POPULATION: Female Balb/c mice with 4T1-luciferase mammary carcinoma cell tumors were administered paclitaxel (PTX; 10 mg/kg), anti-PD1 (200 µg), both, or vehicle (saline) intraperitoneally. Treatment was given on days 0, 2, and 5 for cohort 1 (n=16) who underwent granzyme B specific (GZP) PET imaging (T-cell activation) and days 0, 2, 5, and 8 for cohort 2 (n=12) who underwent [18F]-fluoromisonidazole (FMISO)-PET imaging (hypoxia). Bioluminescence (BLI) imaging and caliper measurements were performed to track tumor size changes at multiple timepoints and tumors were collected for histological validation on day 20. Mean standard uptake value (SUVmean) was calculated as percent of day 0, and statistical analyses were performed with unpaired t-tests and Wilcoxon-rank sum tests. RESULTS/ANTICIPATED RESULTS: Non-responders to treatment had a significantly higher tumor volume compared to responders starting on day 6 (p<0.05). Although no significant differences in BLI between control and single-agent therapies were found, BLI data revealed that treatment with combination PTX and anti-PD1 significantly decreased viability signal between days 3 and 6 (p=0.04). SUVmean from GZP-PET was over 250% higher in responders compared to non-responders by day 6 (p=0.03). SUVmean from FMISO-PET was 80% less in responders compared to nonresponders, indicating less tumor hypoxia (p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Non-invasive PET imaging of the tumor microenvironment can provide data on T cell activation and hypoxic response predicting response to combination immunotherapy and chemotherapy. Utilizing advanced imaging to understand biologically distinct features of the TNBC tumor microenvironment can aid in personalizing anti-cancer therapies.
Paediatric neuroimaging

An increasing number of advanced magnetic resonance (MR) techniques are routinely performed in paediatric neuroradiology departments. The most diffuse technique, standard diffusion weighted imaging, is very fast and is becoming increasingly common in routine practice. The usefulness of calculating apparent diffusion coefficient (ADC) is also well known and frequently used, together with voxel proton spectroscopy. Others techniques such as perfusion or BOLD still have a limited use. The most frequent applications of these techniques are discussed in some of the most representative fields of paediatric neuroradiology.
Interim Results of a Phase II Trial on Hypofractionated Radiation Therapy for Inoperable Soft Tissue Sarcoma.

Purpose/objective(s) For patients with localized soft tissue sarcoma (STS) who cannot or choose not to undergo surgery, radiation alone can be used for local tumor control. Conventionally fractionated radiation has been reported to achieve local control in Materials/methods We are conducting an IRB-approved, single institution, prospective phase II clinical trial enrolling patients with STS that was unresectable or who opted against surgery. Patients underwent HXRT in 8 or fewer fractions using either CT- (11, 61%) or MRI-guided radiation treatments (7, 39%). Data on patient characteristics, radiation, local tumor control, acute and late toxicity, and overall survival was collected. Local control was defined as stable disease, partial response, or complete response on standard-of-care follow up imaging. Toxicity was graded on the Common Terminology Criteria for Adverse Events (CTCAEv5.0) during treatment, at 1 month, and at standard-of-care follow-up visits. Results Eighteen patients were enrolled, 7 with an unresectable primary STS tumor only, 5 with oligometastatic STS, and 6 with widespread metastatic STS. Thirty-eight total lesions were treated - 2 in the neck, 25 in the chest, 1 in the abdomen, 3 in the retroperitoneum, 4 in the pelvis, and 3 in the extremities. Radiation dose ranged from 5-12 Gy per fraction in 3-8 fractions for a total of 18-60 Gy (median dose/fractionation was 50 Gy/5 fractions). Patients were followed for a median of 283 days (range 46 - 532 days). Local tumor control was achieved in all cases for which follow up imaging was obtained (15 patients): 8 patients (53%) had a stable response, 6 (40%) had a partial response, and 1 (7%) had a complete response. Three patients died prior to follow up imaging being obtained. Ten patients (56%) experienced any acute toxicity, with 1 having CTCAE grade 3 toxicity (pain) and 9 having grades 1-2 toxicity, most commonly grade 1-2 arthralgia or myositis (5 patients, 28%). Conclusion Interim analysis of this prospective clinical trial suggests that HXRT can be safely delivered to STS locations throughout the body and provides local tumor control. All evaluable patients exhibit local tumor control thus far, with only 1 acute toxicity of grade 3 or greater. Additional patient enrollment and follow up is needed to further evaluate these outcomes and to evaluate for potential late toxicities.
Abstract 17399: Glutathione-S-Transferase P Regulates Neovascularization in the Remodeling Heart via Effects on Endothelial Progenitor Cells and Reparative Monocytes

Glutathione- S -transferase P (GSTP) modulates c-Jun N-terminal kinase (JNK) activation and the proliferation of bone marrow (BM) myeloid progenitors; however, its effects on endothelial progenitor cells (EPCs) and neovascularization are unknown. Hypothesis: GSTP promotes EPC function in a JNK-dependent manner, thereby supporting neovascularization in heart failure (HF). GSTP-/- mice exhibited significantly (p + CD11b + Gr-1 hi monocytes, diminished BM EPC function (proliferation, migration, and vascular tube formation), and increased BM JNK phosphorylation. These effects were reversed upon treatment with the JNK inhibitor SP600125. HF was induced by left coronary ligation in WT and GSTP-/- mice (sham control). GSTP-/- HF mice exhibited (p + Ly6C hi monocytes, but comparable Ly6C low monocytes at baseline. Moreover, at 3 and 7 d post-ligation, GSTP-/-c HF mice had fewer circulating EPCs and reparative Ly6C low monocytes, but significantly higher Ly6C hi monocytes. Conclusion: GSTP promotes EPC function and reparative monocyte mobilization, and suppresses inflammation, thereby improving angiogenic gene expression, neovascularization and LV remodeling after infarction. Hence, human GSTP polymorphisms, which are frequent, may impact cardiac reparative capacity in patients with myocardial infarction.
A Tutorial on Dynamic and Differential Games

A general formulation of dynamic and differential games is given, which includes both discrete and continuous time problems as well as deterministic and stochastic games. Solution concepts are introduced in two categories, depending on whether the dynamic game is defined in normal or extensive form. For the former, we present the Nash, Stackelberg and Consistent Conjectural Variations (CCV) equilibria, with considerable discussion devoted to the CCV solution, including comparisons with other more specific definitions found in the literature. For games in extensive form, we discuss the feedback solution concepts, and elaborate on the time consistency issue, which is currently of major interest in the economics literature. The chapter concludes with a discussion which puts into proper perspective the topics and contributions of the ten papers to follow, and their relationships with each other.
Superactive inhibitors of angiotensin converting enzyme: analogs of BPP9a containing dehydroproline.

we have synthesized a series of its analogs containing L-3,4dehydroproline [l] (A3Pro) in place of the prolme residues at position 3,5,8 or 9. These analogs were synthesized to facilitiate preparation of tritiumlabelled BPPg, by catalytic hydrogenation in tritium gas of the unsaturated carbon-carbon bond of AaPro. However, during the course of our studies, the A3ProBPP,, analogs were assayed in vitro and in vivo for their abilities to inhibit angiotensin converting enzyme (ACE). All of the analogs were found to be more potent than BPP,, itself. Several bradykinin potentiating peptides (BPP) have been isolated from the venom of Bothrops jararaca, a South American pit viper [2,3]. The most potent is the nonapeptide, BPPg,. Part, if not all, of the effects of BPPg, as a bradykinin potentiating agent are attributable to its ability to inhibit angiotensin converting enzyme [4,5]. Gavras and colleagues [6,7] have shown that BPPg,, injected intravenously at l-4 mg/kg body wt, acts as a potent anti-hypertensive agent in patients with reninrelated hypertension. Of equal or greater importance is that some patients with essential hypertension can also be made normotensive by treatment with BPPg,