cssi/SciSciGPT-SciSciNet huggingface dataset:
Characterizing the roles of changing population size and selection on the evolution of flux control in metabolic pathways

Understanding the genotype-phenotype map is fundamental to our understanding of genomes. Genes do not function independently, but rather as part of networks or pathways. In the case of metabolic pathways, flux through the pathway is an important next layer of biological organization up from the individual gene or protein. Flux control in metabolic pathways, reflecting the importance of mutation to individual enzyme genes, may be evolutionarily variable due to the role of mutation-selection-drift balance. The evolutionary stability of rate limiting steps and the patterns of inter-molecular co-evolution were evaluated in a simulated pathway with a system out of equilibrium due to fluctuating selection, population size, or positive directional selection, to contrast with those under stabilizing selection. Depending upon the underlying population genetic regime, fluctuating population size was found to increase the evolutionary stability of rate limiting steps in some scenarios. This result was linked to patterns of local adaptation of the population. Further, during positive directional selection, as with more complex mutational scenarios, an increase in the observation of inter-molecular co-evolution was observed. Differences in patterns of evolution when systems are in and out of equilibrium, including during positive directional selection may lead to predictable differences in observed patterns for divergent evolutionary scenarios. In particular, this result might be harnessed to detect differences between compensatory processes and directional processes at the pathway level based upon evolutionary observations in individual proteins. Detecting functional shifts in pathways reflects an important milestone in predicting when changes in genotypes result in changes in phenotypes.
Between Backyard Swamps and the Cosmos: Place, Space, and the Intersubjective Mesh in the Poetry of Manoel de Barros

This essay proposes a reading of the poetry of Manoel de Barros oriented by deconstructive turns in contemporary ecocritical theory and debates on the meanings of eco-poetry as a critical designation. I consider the tension between place-based referentiality and abstract spaciousness in Barros’ work as well as the resonance between its microcosmic scenes of abjection, decay and trans guration and ecocritic Timothy Morton’s notion of the intersubjective mesh as the fundamental basis of ecological thinking. While an aura of conservation politics and place-making referentiality can certainly be intuited in Barros’ poetic figurations of Pantanal landscapes, flora, and fauna, I argue that the force of meaning of his ambient poetics is most substantially to be found in their sustained imagining of intersubjectivity and its unsettling ontological and ethical effects.
Computer graphics aid mission operations

The application of computer graphics techniques in NASA space missions is reviewed. Telemetric monitoring of the Space Shuttle and its components is discussed, noting the use of computer graphics for real-time visualization problems in the retrieval and repair of the Solar Maximum Mission. The use of the world map display for determining a spacecraft's location above the earth and the problem of verifying the relative position and orientation of spacecraft to celestial bodies are examined. The Flight Dynamics/STS Three-dimensional Monitoring System and the Trajectroy Computations and Orbital Products System world map display are described, emphasizing Space Shuttle applications. Also, consideration is given to the development of monitoring systems such as the Shuttle Payloads Mission Monitoring System and the Attitude Heads-Up Display and the use of the NASA-Goddard Two-dimensional Graphics Monitoring System during Shuttle missions and to support the Hubble Space Telescope.
Fueling the New Jim Crow: Mass Incarceration & Racial Bias

The history of not only the United States but the world, knows racism all too well. Races and groups have been discriminated against time and time again, solely based on the color of their skin. With these prejudiced people and their views have come racial caste systems, Jim Crow being one of the most widely recognized. Jim Crow laws were local and state laws that imposed racial segregation in the South. More specifically, African-Americans had a “separate but equal” status but were treated far from equally. Their facilities were inferior and underfunded compared to others, or simply inexistent. Jim Crow established countless educational, social, and economic disadvantages for African Americans, ones that are still being felt and channeled today, as Michelle Alexander discusses in her book The New Jim Crow: Mass Incarceration in the Age of Colorblindness and Carson Barlett in the corresponding research paper. Carson, a psychology, multimedia journalism, and political science triple major hoping to attend law school, was inspired to research the social psychological perspective of Alexander’s book when she simultaneously had classes in social psychology and jurisprudence. Black Lives Matter and police brutality were also major topics of national concern, as the Justice Department had recently released its investigative report on the police department in Ferguson, Missouri. Carson recognizes Alexander’s book as a hallmark of modern research on race and mass incarceration, but believes it leaves out a large part of the cause for the problems it discusses, which can be drawn from social psychology. “As racial tensions and police policies continue to plague our political environment, it is important to view these issues through a lens that is informed not only by facts and history, as Alexander analyzes them, but also through the lens of human behavior and expectations,” she says. She hopes that her research gives this second look at these long-lasting issues. Alexander boldly accuses the United States of unfairly targeting blacks as criminals, however she does not believe that people are explicitly racist. Using social psychology, Carson attempts to explain what Alexander does not, which is that race changes the way we behave toward others, whether we are conscious of it or not.
Middle East respiratory syndrome coronavirus: five years later

ABSTRACTIntroduction: In the past five years, there have been 1,936 laboratory-confirmed cases of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 3...
Apex Dips of Experimental Flux Ropes: Helix or Cusp?

We present a new theory for the presence of apex dips in certain experimental flux ropes. Previously such dips were thought to be projections of a helical loop axis generated by the kink instability. However, new evidence from experiments and simulations suggest that the feature is a 2D cusp rather than a 3D helix. The proposed mechanism for cusp formation is a density pileup region generated by nonlinear interaction of neutral gas cones emitted from fast-gas nozzles. The results indicate that density perturbations can result in large distortions of an erupting flux rope, even in the absence of significant pressure or gravitational forces. The density pileup at the apex also suppresses the m = 1 kink mode by acting as a stationary node. Consequently, more accurate density profiles should be considered when attempting to model the stability and shape of solar and astrophysical flux ropes.
Tyrosine kinases wee1 and mik1 as effectors of DNA replication checkpoint control.

Cell cycle studies have revealed mechanisms that prevent cell division if DNA fails to be completely replicated or sustains damage1–3. Here we focus on the evidence from yeast genetics that the wee1 and mik1 tyrosine kinases cooperate in the inhibitory phosphorylation of cdc2p, and the possibility that these kinases function in pathways that ensure the integrity of the genome prior to cell division. We also review the progress in cloning and analysing wee1-like tyrosine kinases from higher eukaryotes, and the evidence for and against their functioning in ensuring DNA replication prior to mitosis. Finally, we discuss the genes involved in these feedback controls and suggest that wee1p and mik1p might be the ultimate effectors that prevent mitosis when a checkpoint is triggered.
The Chemistry of the Optical Constants of Solids

Most ideally, the theoretical solid state physicist would be able to calculate from first principles the linear and non-linear optical constants of practical use. In fact, there are very few calculations in all of solid state physics which can be done from first principles. Instead, there is normally an immense amount of feed-back between theory and experiment in which one evaluates from experiments the theoretical parameters whose meaning is simple but whose calculation is impossible. It is such quasi-first principles calculations which will be described. An alternative form of calculation is pure empiricism, in which one invents new constructs, and checks these constructs against experimental results to find out whether the constructs themselves are valid and useful or not. But the characteristic approach of physics begins at the beginning and goes as far as possible from first principles before using experimental numbers to conceal physical ignorance.
Gnotobiotic and Conventional Mouse Systems to Support Microbiota Based Studies

Animal models are essential to dissect host-microbiota interactions that impact health and the development of disease. In addition to providing pre-clinical models for the development of novel therapeutics and diagnostic biomarkers, mouse systems actively support microbiome studies by defining microbial contributions to normal development and homeostasis, and as well as their role in promoting diseases such as inflammatory auto-immune diseases, diabetes, metabolic syndromes, and susceptibilities to infectious agents. Mice provide a genetically tenable host that can be reared under gnotobiotic (germfree) conditions, allowing colonization studies with human or mouse-origin defined or complex microbial communities to define specific in vivo effects. The protocols and background information detail key aspects to consider in designing host-microbiome experiments with mouse models, and to develop robust systems that leverage gnotobiotic mice, microbial consortia, and specific environmental perturbations to identify causal effects in vivo.
Philosophy against Poetry: The Complicated Relationship of Odysseus and Socrates

I begin by looking at arguments that Plato seeks to positively compare Odysseus to either the just man or the philosopher of the Republic, or even to Socrates himself. I then turn to an analysis of the Lesser Hippias, in which Socrates elevates Odysseus above Achilles as the best of the Homeric heroes. Finally, I turn to the several implicit Socratic criticisms of Odysseus in the Platonic corpus to make the case that, despite any perceived superiority to Achilles, Odysseus cannot compare favorably with Socrates, whose moral heroism far surpasses that of the suffering of the Homeric hero.
The Randolph W. Thrower Symposium: Business Law: The Impact of Competition on Regulation - Introduction

The focus of the 2003 Emory Law Journal Randolph Thrower Symposium was on the impact of competition on regulation. Judge Frank Easterbrook warns of the public expense incurred for private gains in regulation, and of the rate of judicial error in antitrust regulation. Fred McChesney traces the intellectual history of the battle for the soul of antitrust, and the regulatory competition among state, federal and international regulators to be the most restrictive and visible regulators of the field. George Benston traces the failures of regulation that led to Enron and Sarbanes-Oxley, blaming lawyers, accountants and regulators for a move from standards to rules. Barry Adler and Henry Butler examine Delaware's current prominence in Chapter 11 reorganization, and argue that no theory supports a prediction of permanent preeminence of the kind observed in corporate law. Jonathan Macy traces the internationalization of regulation, and describes three forces that create international uniformity in regulation, while Henry Manne imagines a corporate world without regulation.
Uterine Cancer: The Influence of Genetics and Environment on Cell Cycling Pathways in Cancer

Endometrial cancer is the most common gynecologic malignancy in the USA and is becoming increasingly more prevalent in industrialized countries. Endometrial cancer accounts for over 43,000 new cases (6% of all cancer cases) and almost 8,000 deaths annually (3% of cancer deaths). This chapter reviews current knowledge about endometrial cancer and its implication for strategies at prevention and treatment, with a particular focus on molecular mechanisms of pathogenesis and targeted therapies.
Real Time and Mapping Spectroscopic Ellipsometry of Hydrogenated Amorphous and Nanocrystalline Si Solar Cells

Real time spectroscopic ellipsometry (SE) has been applied to characterize the structural evolution and optical properties of the critical p-type doped and intrinsic hydrogenated silicon (Si:H) layers that comprise the nanocrystalline Si:H bottom cell of tandem photovoltaic (PV) devices. The tandem PV devices under study are fabricated in the amorphous/nanocrystalline Si:H (a-Si:H/nc-Si:H) p-i-n superstrate configuration in which the nc-Si:H cell is at the bottom of the device structure due to its narrower bandgap relative to that of the top cell a-Si:H. SE data collected in real time during Si:H solar cell fabrication by plasma enhanced chemical vapor deposition (PECVD) enable identification of Si crystallite development in the bottom cell p and i-layers through the evolution of surface roughness, as well as through variations in the optical properties in the form of the complex dielectric function \( (\varepsilon = \varepsilon_{1} - {\text{i}}\varepsilon_{2} ) \). Analysis of the dielectric function permits quantification of the relative amounts of the a-Si-H and nc-Si-H components that exist during the growth of mixed-phase Si:H layers. Based on these real time SE analysis results, a PECVD growth evolution diagram has been developed for the bottom cell i-layer of the tandem PV cell in order to guide fabrication in this device configuration. Correlations between the p and i-layer structures and device performance are evident and can be understood on the basis of the growth evolution diagram. A second growth evolution diagram has been developed to characterize PECVD of n-type Si-H thin films for use as the n-layer component of p-i-n a-Si:H top cells in the same superstrate configuration. This growth evolution diagram has been established to provide guidance for PECVD of the n-layers over the 15 cm × 15 cm areas of glass/TCO/p/i superstrates, where TCO represents the transparent conducting oxide layer serving as the topmost contact. The goal of this study is to correlate the structural characteristics provided by the diagram with the performance parameters of single-junction a-Si:H solar cells that can serve as the top cell of the tandem device. A 16 × 16 array of p-i-n dot cells has been fabricated over the 15 cm × 15 cm area of the TCO coated glass superstrate, and this same area has been studied by mapping SE. Analysis of the SE data collected over the full area provides maps of the p-layer effective thickness, i-layer thickness and bandgap, and n-layer thickness and nanocrystalline volume fraction for spatial correlation with the performance parameters from current density-voltage (J-V) measurements of the 16 × 16 array of dot cells. The goal of the correlations that exploit mapping SE is to identify and understand the relationships between the variations in the basic materials properties and in the thin film solar cell performance over large areas. The results also enable analysis of the impacts of spatial non-uniformities on PV module performance.
The Environmental Policy Paradox (1-download)

This book examines environmental policy in the United States in air, water, land use, agriculture, energy, waste disposal, and other areas. It discusses the legal processes that come into play when citizens pursue environmental policy goals in the courts.
Heritability and evolvability of morphological traits of Savannah sparrows (Passerculus sandwichensis) breeding in agricultural grasslands

Heritability and evolvability estimates of adult traits from free-living bird populations can be used to gauge the ability of populations to respond to selection, but are rare due to difficulties in gathering detailed pedigree information. The capacity to respond to selection is particularly important for species occupying managed habitats such as agricultural grasslands because of the potential for humans to accidentally influence traits. We calculated heritability and evolvability of six morphological traits in a population of Savannah Sparrows (Passerculus sandwichensis) breeding in a large agricultural landscape. We used microsatellite analysis to determine a genetic pedigree, revealing a high level of extra-pair paternity (63%) within a relatively philopatric population. For the entire population, heritabilities varied from low to high (bill width: 0.160±0.182 to tarsus length: 0.651±0.155), while evolvabilities were low across all traits (wing length: 0.035±0.013 to body mass: 0.066±0.106). Our results indicate that any directional selection from agricultural management practices will produce negligible changes in basic morphometrics of Savannah sparrow populations occupying the Champlain Valley of Vermont, USA.
Multifocal pleomorphic dermal sarcoma and the role of inflammation and immunosuppression in a lung transplant patient: a case report

Pleomorphic dermal sarcoma is the cutaneous variant of undifferentiated pleomorphic sarcoma. It is a rare malignancy of unclear histogenesis; it is a diagnosis of exclusion that requires extensive use of immunohistochemistry to rule out other malignancies. Pleomorphic dermal sarcoma typically presents as a solitary tumor in sun-exposed areas and may have unpredictable clinical behavior, with some tumors associated with metastasis and death. We present an unusual case of multifocal pleomorphic dermal sarcoma arising in the areas of alpha-1-antitrypsin deficiency panniculitis in a lung transplant patient. Our patient was a 58-year-old white woman whose initial presentation was consistent with alpha-1-antitrypsin deficiency panniculitis. She then developed extensive multifocal, bleeding, and ulcerated nodules in the areas of the panniculitis. A skin biopsy was consistent with a diagnosis of pleomorphic dermal sarcoma. Her immunosuppressive regimen was decreased, and she was treated with liposomal doxorubicin 40 mg/m2 every 3 weeks with some initial improvement in the size of her tumors. However, soon after beginning therapy, she developed pneumonia and septic shock and ultimately died from multi-organ failure. We hypothesize that chronic, multifocal inflammation in the skin in the setting of immunosuppression led to simultaneous, malignant transformation in numerous skin lesions. We discuss the challenges of diagnosing pleomorphic dermal sarcoma, therapeutic options, and stress the need for multidisciplinary management of these cases.
Pediatric Palliative Care in the Perioperative Period

The purpose of this review is to familiarize anesthesiologists with the role of the subspecialty of pediatric palliative care and its potential contributions to the management of children with complex and life-threatening illnesses, many of whom may present for operative or diagnostic procedures requiring anesthesia. Recent publications highlight the benefits of palliative care to patients and families experiencing a wide variety of conditions along the continuum from prenatal application to the management of young adults. Retrospective reports highlight improved quality of life, improved symptom control, an impact on place of care, and an increased rate of achieving the preferred place of death. Pediatric palliative care is a relatively new subspecialty of pediatrics which utilizes an interdisciplinary team approach to support patients and their families undergoing treatment for life-threatening or life-limiting conditions, addressing physical, emotional, and psychological needs to care for the whole patient.
Prediction of Compressive Strength of Concrete: Critical Comparison of Performance of a Hybrid Machine Learning Model with Standalone Models

AbstractThe use of machine learning (ML) techniques to model quantitative composition–property relationships in concrete has received substantial attention in the past few years. This paper present...
Clostridioides difficile Infection in Children With Inflammatory Bowel Disease

BACKGROUND The study's objective was to investigate the incidence and risk factors associated with Clostridioides difficile (previously known as Clostridium) infection (CDI) in children with inflammatory bowel disease (IBD) in the province of Manitoba. METHODS Our longitudinal population-based cohort was comprised of all children and young adults aged <17 years diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. The Fisher exact test was used to examine the relationship between categorical variables. A Cox regression model was used to estimate the risk of CDI development in IBD patients. RESULTS Among 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years, and the median age at diagnosis (interquartile range) was 12.96 (9.33-15.81) years. The incidence rates of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (P = 0.46). Compared with children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (adjusted hazard ratio [aHR], 4.38; 95% confidence interval [CI], 1.46-13.10) and anti-tumor necrosis factor (anti-TNF) biologics (aHR, 3.31; 95% CI, 1.11-9.90). The recurrence rate of CDI in our pediatric IBD population was 25%. CONCLUSIONS Our findings confirm that children with IBD are at high risk of developing CDI, which may predict future escalation of IBD therapy.
Should We Use Closing Prices? Institutional Price Pressure at the Close

Closing auctions set daily closing prices for U.S. stocks and account for a striking 7.5% of daily volume in 2018, up from 3.1% in 2010. We study the causes and implications of this major trend. Difference-in-difference analyses suggest that closing volume is fueled directly and indirectly by the growth of indexing and ETFs. Auctions usually match large volume cheaply. However, we identify several concerns. The auction price almost never settles within the bid-ask spread, mostly due to the binding tick size. Auction price deviations revert quickly and completely. Finally, as trading migrates to the close, liquidity at the open worsens.
Perceived safety of cannabis intoxication predicts frequency of driving while intoxicated

Abstract Driving under the influence of cannabis (DUIC) is a public health concern, and data are needed to develop screening and prevention tools. Measuring the level of intoxication that cannabis users perceive as safe for driving could help stratify DUIC risk. This study tested whether intoxication levels perceived as safe for driving predicted past-month DUIC frequency. Online survey data were collected in 2017 from a national sample of n = 3010 past-month cannabis users with lifetime DUIC (age 18+). Respondents indicated past-month DUIC frequency, typical cannabis intoxication level (1–10 scale), and cannabis intoxication level perceived as safe for driving (0–10 scale). Approximately 24%, 38%, 13%, and 24% of respondents engaged in DUIC on 0, 1–9, 10–19, and 20–30 days respectively in the past month. Among these four DUIC frequency groups, median typical intoxication varied little (5–6), but median intoxication perceived as safe for driving varied widely (3–8). Higher intoxication levels perceived as safe for driving corresponded to frequent DUIC (Spearman's rho: 0.46). For each unit increase in intoxication level perceived as safe for driving, the odds of past-month DUIC increased 18% to 68% (multinomial logistic regression odds ratio - MOR1–9 days: 1.18, 95% CI: 1.13–1.23; MOR10–19 days: 1.40, 95% CI: 1.30–1.50; MOR20–30 days: 1.68, 95% CI: 1.57–1.80). In this targeted sample of past-month cannabis users, DUIC frequency varied widely, but daily/near-daily DUIC was common (24%). Measuring intoxication levels perceived as safe for driving permits delineation of past-month DUIC frequency. This metric has potential as a component of public health prevention tools.
Chapter 11 – Neutrophil Function

Publisher Summary This chapter provides an overview of the mechanisms of neutrophil adherence, chemotaxis, phagocytosis, and organism killing. Pluripotential hematopoietic stem cells in the bone marrow differentiating in response to specific growth factors give rise to committed progenitors and then neutrophils. These cells are characterized by their multilobed nuclei and abundant granules in the cytoplasm. Mature neutrophils do not multiply, but instead, are continuously replaced. Neutrophils circulate in the blood for only a few hours and survive in the tissue for only a few days; however, this can be extended by a day or two upon their exposure to various activating agents at sites of inflammation. Neutrophils eventually succumb to programmed cell death by an intrinsic or extrinsic apoptotic pathway. Once neutrophils are recruited into the underlying tissue from the blood and encounter a microorganism, they phagocytize and kill the pathogen to eliminate the infection. This chapter discusses congenital and acquired defects in neutrophil function that predispose animals to infection. The chapter also elaborates in detail neutrophil-mediated tissue injury.
Bottomonium suppression and elliptic flow from real-time quantum evolution

Abstract We compute the suppression and elliptic flow of bottomonium using real-time solutions to the Schrodinger equation with a realistic in-medium complex-valued potential. To model the initial production, we assume that, in the limit of heavy quark masses, the wave-function can be described by a lattice-smeared (Gaussian) Dirac delta wave-function. The resulting final-state quantum-mechanical overlaps provide the survival probability of all bottomonium eigenstates. Our results are in good agreement with available data for R A A as a function of N part and p T collected at s NN = 5.02 TeV. In the case of v 2 for the various states, we find that the path-length dependence of ϒ ( 1 s ) suppression results in quite small v 2 for ϒ ( 1 s ) . Our prediction for the integrated elliptic flow for ϒ ( 1 s ) in the 10 − 90 % centrality class is v 2 [ ϒ ( 1 s ) ] = 0.0026 ± 0.0007 . We additionally find that, due to their increased suppression, excited bottomonium states have a larger elliptic flow and we make predictions for v 2 [ ϒ ( 2 s ) ] and v 2 [ ϒ ( 3 s ) ] as a function of centrality and transverse momentum. Similar to prior studies, we find that it is possible for bottomonium states to have negative v 2 at low transverse momentum.
Evaluating the Utility of Permethylated Polysaccharide Solution NMR Data for Characterization of Insoluble Plant Cell Wall Polysaccharides

Plant cell wall polysaccharide analysis encompasses the utilization of a variety of analytical tools, including gas and liquid chromatography, mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. These methods provide complementary data, which enable confident structural proposals of the many complex polysaccharide structures that exist in the complex matrices of plant cell walls. However, cell walls contain fractions of varying solubilities, and a few techniques are available that can analyze all fractions simultaneously. We have discovered that permethylation affords the complete dissolution of both soluble and insoluble polysaccharide fractions of plant cell walls in organic solvents such as chloroform or acetonitrile, which can then be analyzed by a number of analytical techniques including MS and NMR. In this work, NMR structure analysis of 10 permethylated polysaccharide standards was undertaken to generate chemical shift data providing insights into spectral changes that result from permethylation of polysaccharide residues. This information is of especial relevance to the structure analysis of insoluble polysaccharide materials that otherwise are not easily investigated by solution-state NMR methodologies. The preassigned NMR chemical shift data is shown to be vital for NMR structure analysis of minor polysaccharide components of plant cell walls that are particularly difficult to assign by NMR correlation data alone. With the assigned chemical shift data, we analyzed the permethylated samples of destarched, alcohol-insoluble residues of switchgrass and poplar by two-dimensional NMR spectral profiling. Thus, we identified, in addition to the major polysaccharide components, two minor polysaccharides, namely, <5% 3-linked arabinoxylan (switchgrass) and <2% glucomannan (poplar). In particular, the position of the arabinose residue in the arabinoxylan of the switchgrass sample was confidently assigned based on chemical shift values, which are highly sensitive to local chemical environments. Furthermore, the high resolution afforded by the 1H NMR spectra of the permethylated switchgrass and poplar samples allowed facile relative quantitative analysis of their polysaccharide composition, utilizing only a few milligrams of the cell wall material. The concepts herein developed will thus facilitate NMR structure analysis of insoluble plant cell wall polysaccharides, more so of minor cell wall components that are especially challenging to analyze with current methods.
Anthrax lethal factor cleaves regulatory subunits of phosphoinositide-3 kinase to contribute to toxin lethality

Anthrax lethal toxin (LT), produced by Bacillus anthracis, comprises a receptor-binding moiety, protective antigen and the lethal factor (LF) protease1,2. Although LF is known to cleave mitogen-activated protein kinase kinases (MEKs/MKKs) and some variants of the NLRP1 inflammasome sensor, targeting of these pathways does not explain the lethality of anthrax toxin1,2. Here we report that the regulatory subunits of phosphoinositide-3 kinase (PI3K)-p85α (PIK3R1) and p85β (PIK3R2)3,4-are substrates of LF. Cleavage of these proteins in a proline-rich region between their N-terminal Src homology and Bcr homology domains disrupts homodimer formation and impacts PI3K signalling. Mice carrying a mutated p85α that cannot be cleaved by LF show a greater resistance to anthrax toxin challenge. The LF(W271A) mutant cleaves p85α with lower efficiency and is non-toxic to mice but can regain lethality when combined with PI3K pathway inhibitors. We provide evidence that LF targets two signalling pathways that are essential for growth and metabolism and that the disabling of both pathways is likely necessary for lethal anthrax infection.
How Should Ethics Consultants Weigh the Law (and other Authoritative Directives)

In the continuing debate about the role of the Clinical Ethics Consultant in performing clinical ethics consultations, it is often assumed that consultants should operate within ethical and legal standards. Recent scholarship has focused primarily on clarifying the consultant's role with respect to the ethical standards that serve as parameters of consulting. In the following, however, I wish to address the question of how the ethics consultant should weigh legal standards and, more broadly, how consultants might weigh authoritative directives, whether legal, institutional, or professional, against other normative considerations. I argue that consultants should reject the view that authoritative directives carry exclusionary reason for actions and, further, ethicists should interpret directives as lacking any moral weight qua authoritative directive. I then identify both implications and limitations of this view with respect to the evolving role of the ethics consultant in an institutional setting, and in doing so propose the kinds of considerations the ethicist should weigh when presented with an authoritative directive.
Transesophageal Echocardiography Performed by Intensivist and Emergency Physicians-A 5-Year, Single-Center Experience.

Purpose: Data on the use of transesophageal echocardiography (TEE) by intensivist physicians (IP) and emergency physicians (EP) are limited. This study aims to characterize the use of TEE by IPs an...
Understanding Heat Transfer During the Secondary Drying Stage of Freeze Drying: Current Practice and Knowledge Gaps.

Abstract Currently, there is a lack of robust models for secondary drying with comparable accuracy and flexibility as primary drying models. In order to better understand heat transfer during secondary drying, sucrose and mannitol solutions were freeze-dried in vials in a lab-scale lyophilizer under various drying conditions. Several distinct thermal characteristics for secondary drying were experimentally observed: (1) the vial heat transfer coefficient can change significantly between primary and secondary drying due to the change in water vapor content in the freeze dryer; (2) the thermal mass of the vial plays a major role in determining the cake temperature as roughly 95% of the heat supplied is absorbed by the vial walls. From a theoretical perspective, three different models of secondary drying were examined with varying degrees of complexity (full 3D simulation, 1D-averaged equations, and lumped-capacitance 0D approach). In these models, the desorption of bound water is treated as a one-way coupling with temperature. It is found that although a simple lumped-capacitance approach can capture many of the vital features of cake temperature and moisture profile, near quantitative agreement with experiments can be made by employing a 1D-averaged equation approach, where the effective thermal conductivities of the vial are determined by thermal circuits.
Thermal management materials for energy-efficient and sustainable future buildings

Thermal management plays a key role in improving the energy efficiency and sustainability of future building envelopes. Here, we focus on the materials perspective and discuss the fundamental needs, current status, and future opportunities for thermal management of buildings. First, we identify the primary considerations and evaluation criteria for high-performance thermal materials. Second, state-of-the-art thermal materials are reviewed, ranging from conventional thermal insulating fiberglass, mineral wool, cellulose, and foams, to aerogels and mesoporous structures, as well as multifunctional thermal management materials. Further, recent progress on passive regulation and thermal energy storage systems are discussed, including sensible heat storage, phase change materials, and radiative cooling. Moreover, we discuss the emerging materials systems with tunable thermal and other physical properties that could potentially enable dynamic and interactive thermal management solutions for future buildings. Finally, we discuss the recent progress in theory and computational design from first-principles atomistic theory, molecular dynamics, to multiscale simulations and machine learning. We expect the rational design that combines data-driven computation and multiscale experiments could bridge the materials properties from microscopic to macroscopic scales and provide new opportunities in improving energy efficiency and enabling adaptive implementation per customized demand for future buildings.
Reflections on an academic life

David Harvey traces his intellectual journey reflecting on what he calls “the central animating theme of his thinking” starting from his days as a positivist geographer and the publication of Expla...
Preliminary evaluation of convective heat transfer in a water shield for a surface power reactor

As part of the Vision for Space Exploration, the end of the next decade will bring man back to the surface of the moon. A crucial issue for the establishment of human presence on the moon will be the availability of compact power sources. This presence could require greater than 10's of kWt's in follow on years. Nuclear reactors are well suited to meet the needs for power generation on the lunar or Martian surface. Radiation shielding is a key component of any surface power reactor system. Several competing concepts exist for lightweight, safe, robust shielding systems such as a water shield, lithium hydride (LiH), and boron carbide. Water offers several potential advantages, including reduced cost, reduced technical risk, and reduced mass. Water has not typically been considered for space reactor applications because of the need for gravity to fix the location of any vapor that could form radiation streaming paths. The water shield concept relies on the predictions of passive circulation of the shield water by natural convection to adequately cool the shield. This prediction needs to be experimentally evaluated, especially for shields with complex geometries. NASA Marshall Space Flight Center has developed the experience and facilities necessary to do this evaluation in its Early Flight Fission - Test Facility (EFF-TF).
Numerical Techniques and Cloud-Scale Processes for High-Resolution Models

Abstract : The long-term goal of this project is to improve the existing U.S. Navy mesoscale atmospheric forecast model, the Coupled Ocean/Atmosphere Mesoscale Prediction System (COAMPS (trademark)), and maintain it at the leading edge of Numerical Weather Prediction (NWP) models, while at the same time continue developing the next-generation model. In the near future, a change of paradigm to a unified approach in NWP will necessitate a novel approach in modeling. The project has two main objectives. First, to continue development of the model based on Spectral Element (SE) methods and evaluate detailed simulations in two-dimensions (2D) and preliminary tests in three dimensions (3D). In addition, improvements to the numerical temporal integration scheme will be sought. Second, to improve the current generation version of COAMPS by implementing state-of-the-science numerical methods such as Weighted Essentially Non-Oscillatory (WENO) based methods for tracer transport and semi-lagrangian time stepping for improved model efficiency. In our two-pronged approach, we will leverage our efforts to advance both the SE model and COAMPS.
Priority algorithm for near-data scheduling: Throughput and heavy-traffic optimality

The prevalence of data-parallel applications has made near-data scheduling an important problem. An example is the map task scheduling in the map-reduce framework. Wang et. al. [13] was the first to identify its capacity region and proposed a throughput-optimal algorithm based on MaxWeight. However, the study of the algorithm's delay performance revealed that it is only heavy-traffic optimal for a very special traffic scenario, where all traffic concentrates on a subset of servers. We propose a simple “local-tasks first” priority algorithm and show that it is throughput-optimal and heavy-traffic optimal for all traffic scenarios, i.e., it asymptotically minimizes the average delay as the arrival rate vector approaches the boundary of the capacity region. So far, it is the only known heavy-traffic optimal algorithm for this setting. As the algorithm is based on pre-determined priority, a direct application of the Lyapunov drift technique does not work. The main proof ideas are the construction of an ideal load decomposition and the separate treatment of two subsystems based on their ideal load. To the best of our knowledge, this is the only setup of affinity scheduling where a simple priority algorithm is shown to be heavy-traffic optimal. Simulation shows that our algorithm also significantly outperforms existing algorithms at loads away from the boundary of the capacity region.
Online detection and modeling of safety boundaries for aerospace applications using active learning and Bayesian statistics

The behavior of complex aerospace systems is governed by numerous parameters. For safety analysis it is important to understand how the system behaves with respect to these parameter values. In particular, understanding the boundaries between safe and unsafe regions is of major importance. In this paper, we describe a hierarchical Bayesian statistical modeling approach for the online detection and characterization of such boundaries. Our method for classification with active learning uses a particle filter-based model and a boundary-aware metric for best performance. From a library of candidate shapes incorporated with domain expert knowledge, the location and parameters of the boundaries are estimated using advanced Bayesian modeling techniques. The results of our boundary analysis are then provided in a form understandable by the domain expert. We illustrate our approach using a simulation model of a NASA neuro-adaptive flight control system, as well as a system for the detection of separation violations in the terminal airspace.
A tool for formatting computer science lectures in HTML

This paper advocates using HTML for representing Computer Science lectures. This technology should be at least as good as popular presentation-packages such as Microsoft PowerPoint, being able to handle multimedia. Beyond that, HTML can conveniently handle material in chunks larger than a screenful, it can be used in more computer-systems, and it is more extensible.This paper further presents a package which formats lectures in HTML. Features of this package particularly suited for lectures include. (i) enabling private lecture-notes to be interspersed with the lecture-materials that will be publicly displayed, and (ii) arranging for some texts to be filled in during presentations of lectures, which induces students to be somewhat involved.
How else can we study sex differences in early infancy

This paper revisits group difference and individual variability in birth weight, head size, Apgar score, and motor performance in neonatal and 8-month-old males and females using a large existing data set. The goal is primarily theoretical--to reframe existing analyses with an eye toward designing and executing more predictive analyses in the future. 3D graphing to visualize both the areas of overlap and regions of disparity between boys and girls has been used. A two-step cluster analysis of boys and girls together revealed three clusters. One was almost equally divided between boys and girls, but a second was highly enriched for boys and the third highly skewed toward girls. The relationship between cluster membership and Bayley motor scores at 8 months tested the hypothesis that initial differences that have no sex-related behavioral content might start processes that produce later sex-related differences. Initially, parental belief systems may be less important than infant care patterns evoked by basic size and health characteristics, even though later parental behaviors assume a decidedly gendered pattern.
On wave propagation in an inhomogeneous non–stationary medium with an inhomogeneous non-stationary flow

An approximate wave equation that models scalar wave propagation in a moving fluid whose ambient properties and flow are inhomogeneous both in space and time is considered. Asymptotic solutions for both non–caustic and caustic regions and some Hamiltonian properties of the equation in both non–caustic and caustic regions are developed.
Soluble proteins and quantitative analysis of protein and RNA during oogenesis in Necturus maculosus.

Abstract 1. 1. The amount of RNA and protein in the Necturus oocyte increases during the course of oogenesis. The greatest increase occurs in oocytes ranging from 1.3–2.5 mm in diameter. 2. 2. In the follicle envelope, the amount of RNA also increases during oogenesis. The greatest increase occurs as oocytes grow from 1–2.5 mm in diameter. Protein increase in the follicle envelope is associated with occyte growth from 2.5–5 mm. 3. 3. Soluble proteins of developing oocytes increase to a maximum [25] in oocytes 1.25 mm in diameter. At this time a visual band for band comparison of soluble proteins in the oocyte and liver (also [25]) is evident. The number of soluble proteins decrease during subsequent periods of oocyte growth and new bands become evident. Analysis of soluble proteins in the blood serum and other body organs is included. 4. 4. The number of soluble proteins in the follicle envelope is less than the number in the oocyte, but the pattern of change in soluble proteins of the follicle envelope parallels that in the oocyte.
Comparison of stress indices in gauging clinical activity in patients with inflammatory bowel disease

Stress indices are widely available but few have been validated or used for monitoring clinical disease activity in chronic inflammatory disorders. One hundred twenty-three outpatients with inflammatory bowel disease (IBD) participated in this prospective investigation. Stress events (major events, daily strains, perceived stress) and disease activity were monitored for six consecutive follow-ups using standardized instruments. We present effect estimates of daily strains on clinical disease activity separately from the effect of major stress events. Our results indicate that the stress measures were moderately correlated, correlation coefficients ranged from .64 to .66. In relation to disease, self-perceived stress using a stress ladder (r=.31, p<.001) was comparable to probing stress event checklists (major events:r=.34, p<.001; daily strains:r=.20, p=NS). A multiple linear regression analysis revealed that each of the three methods of evaluating stress makes a significant contribution, even after adjustment for potential confounders. No substantial increase in the proportion of explained variance was evident in an analysis based on a composite index of major events and daily strains. A clinical implication of these results is that while self-perceptions of emotional stress may be less objective measures, influencing changes in stress perceptions may be useful in the treatment and prevention of IBD.
Interactions of zeatin with gold ions and biomimetic formation of gold complexes and nanoparticles

Abstract We report here a simple one-pot synthesis for the preparation of gold nanoparticles biomimetically using zeatin nanostructures. Zeatin, a plant phytohormone was self-assembled into nanospheres. Those nanospheres transformed into nanoribbons over a period of time upon formation of zeatin–gold (III) complexes in the presence of hydrogen tetrachloroaurate. Further, upon heating, gold nanoparticles were formed due to mineralization in the presence of zeatin nanofibers. The effect of pH on the self-assembly of zeatin and the formation of gold nanoparticles, was investigated. We also compared the preparation of gold nanoparticles in the presence of zeatin nanoribbons, using a known reducing agent such as hydrazine, which resulted in loss of morphology control and alignment of the gold nanoparticles. Thus zeatin nanoribbons act as templates which allow for size as well as alignment control for the gold nanoparticles. The materials obtained were analyzed using FTIR, absorbance spectroscopy as well as by transmission electron microscopy, EDX, SEM and AFM. The method involved here is a mild, green-synthetic process, which could be used for facile preparation of morphology controlled gold nanoparticles and may open up new avenues for device fabrications for a wide range of applications, particularly in optoelectronics and sensors.