cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of Cytochrome P450 (CYP450) Isoforms by Isoniazid: Potent Inhibition of CYP2C19 and CYP3A

Isoniazid (INH) remains the most safe and cost-effective drug for the treatment and prophylaxis of tuberculosis. The use of INH has increased over the past years, largely as a result of the coepidemic of human immunodeficiency virus infection. It is frequently given chronically to critically ill patients who are coprescribed multiple medications. The ability of INH to elevate the concentrations in plasma and/or toxicity of coadministered drugs, including those of narrow therapeutic range (e.g., phenytoin), has been documented in humans, but the mechanisms involved are not well understood. Using human liver microsomes (HLMs), we tested the inhibitory effect of INH on the activity of common drug-metabolizing human cytochrome P450 (CYP450) isoforms using isoform-specific substrate probe reactions. Incubation experiments were performed at a single concentration of each substrate probe at its K(m) value with a range of INH concentrations. CYP2C19 and CYP3A were inhibited potently by INH in a concentration-dependent manner. At 50 microM INH (approximately 6.86 microg/ml), the activities of these isoforms decreased by approximately 40%. INH did not show significant inhibition (<10% at 50 microM) of other isoforms (CYP2C9, CYP1A2, and CYP2D6). To accurately estimate the inhibition constants (K(i) values) for each isoform, four concentrations of INH were incubated across a range of five concentrations of specific substrate probes. The mean K(i) values (+/- standard deviation) for the inhibition of CYP2C19 by INH in HLMs and recombinant human CYP2C19 were 25.4 +/- 6.2 and 13 +/- 2.4 microM, respectively. INH showed potent noncompetitive inhibition of CYP3A (K(i) = 51.8 +/- 2.5 to 75.9 +/- 7.8 microM, depending on the substrate used). INH was a weak noncompetitive inhibitor of CYP2E1 (K(i) = 110 +/- 33 microM) and a competitive inhibitor of CYP2D6 (K(i) = 126 +/- 23 microM), but the mean K(i) values for the inhibition of CYP2C9 and CYP1A2 were above 500 microM. Inhibition of one or both CYP2C19 and CYP3A isoforms is the likely mechanism by which INH slows the elimination of coadministered drugs, including phenytoin, carbamazepine, diazepam, triazolam, and primidone. Slow acetylators of INH may be at greater risk for adverse drug interactions, as the degree of inhibition was concentration dependent. These data provide a rational basis for understanding drug interaction with INH and predict that other drugs metabolized by these two enzymes may also interact.
The information text gap: The mismatch between non-narrative text types in basal readers and 2009 NAEP recommended guidelines.

The purpose of this study was to compare the text genres represented in two recent California-adopted basal readers (grades 1 through 6) with the guidelines for informational text types in the 2009 NAEP framework. Phase 1 of data collection involved the use of two measures to determine the presence of each text genre: number of pages and number of selections. The researchers assigned pages and selections to one of four categories: narrative, poetry, play, or nonfiction. The second phase of data collection involved classification of nonfiction selections according to one of four categories: literary nonfiction, or one of three types of informational text: expository, argumentation and persuasive, or procedural and documents. The researchers computed percentages of pages and selections devoted to each genre and each type of nonfiction across grade levels and series. Results overall indicated that 40% of pages/selections in both series were devoted to nonfiction text, and that 50% of nonfiction text selectio...
Generalized approach for modeling minimally invasive surgery as a stochastic process using a discrete Markov model

Minimally invasive surgery (MIS) involves a multidimensional series of tasks requiring a synthesis between visual information and the kinematics and dynamics of the surgical tools. Analysis of these sources of information is a key step in defining objective criteria for characterizing surgical performance. The Blue DRAGON is a new system for acquiring the kinematics and the dynamics of two endoscopic tools synchronized with the endoscopic view of the surgical scene. Modeling the process of MIS using a finite state model [Markov model (MM)] reveals the internal structure of the surgical task and is utilized as one of the key steps in objectively assessing surgical performance. The experimental protocol includes tying an intracorporeal knot in a MIS setup performed on an animal model (pig) by 30 surgeons at different levels of training including expert surgeons. An objective learning curve was defined based on measuring quantitative statistical distance (similarity) between MM of experts and MM of residents at different levels of training. The objective learning curve was similar to that of the subjective performance analysis. The MM proved to be a powerful and compact mathematical model for decomposing a complex task such as laparoscopic suturing. Systems like surgical robots or virtual reality simulators in which the kinematics and the dynamics of the surgical tool are inherently measured may benefit from incorporation of the proposed methodology.
Current account balances, financial development and institutions: Assaying the world “saving glut”

We investigate the medium-term determinants of the current account using a model that controls for factors related to institutional development, with a goal of informing the recent debate over the existence and relevance of the “savings glut.” The economic environmental factors that we consider are the degree of financial openness and the extent of legal development. We find that for industrial countries, the government budget balance is an important determinant of the current account balance; the budget balance coefficient is 0.21 in a specification controlling for institutional variables. More interestingly, our empirical findings are not consistent with the argument that the more developed financial markets are, the less saving a country undertakes. We find that this posited relationship is applicable only for countries with highly developed legal systems and open financial markets. For less developed countries and emerging market countries we usually find the reverse correlation; greater financial development leads to higher savings. Furthermore, there is no evidence of “excess domestic saving” in the Asian emerging market countries; rather they seem to have suffered from depressed investment in the wake of the 1997 financial crises. We also find evidence that the more developed equity markets are, the more likely countries are to run current account deficits.
Sex differentiation by leukocyte morphology.

Following the observations of Barr and Bertram in 1949 (1) on the neurones of cats, several workers have shown that the sex of certain mammals can be clearly identified from the microscopic appearance of the cells of various tissues (2–7). Graham (8) showed that in the embryo this specificity antedates sexual differentiation of the gonads. Moore and Barr(9) investigated numerous human tissues which demonstrate sex differences of morphology. Studies of the cell nuclei of the skin in biopsy specimens have been used in investigations on hermaphrodites and other ababnormal individuals (10–13). The sex morphology of teratomas and other tumors is under study (14–17) and preliminary reports have appeared on the sex differences of the cells in scrapings of the oral mucosa (18, 19).
Estimates of solar wind heating inside 0.3 AU

Helios 1 proton temperature data have been normalized in order to determine a base temperature-velocity curve at 0.3 AU and to provide quantitative estimates on the close-in heating at different solar wind velocities. The results suggest that the slope of the solar wind temperature gradients for high-speed streams inside 0.3 AU is about half of that found beyond it. The very-low-speed wind is shown to expand adiabatically all the way out. It is also found that intermediate speed winds have enhanced heating rates in proportion to their velocities.
Marine sensors for open sea berth terminals

The purpose of this paper is to present the trend and a predictable evolution in ship mooring and harbor engineering and to recommend the development of an integrated system of marine sensors for open sea berth terminals. The evolution toward the open sea berth type terminal is the result of a number of factors, which all may not have been fully mastered in the past but are now within the grasp of existing technology. These are: 1) a better knowledge of the sea environments (wind, wave, current statistics); 2) a systematic use of flexible dolphins, flexible fenders, nylon tails, constant tension winches (on board or fixed on berth), and flexible loading arms (Chicksan); and 3) an understanding of moored ship dynamics by use of mathematical model and/or scale model. Based on these, it would then appear that the cost of breakwater cannot be justified in many cases. The development of operational port code based on real-time operational sensors of all the critical elements will further enhance the safety of operations at berth.
Standardization of Health Care Provider Competencies for Intrathecal Access Procedures

Introduction: This quality improvement (QI) project addresses a method for experienced health care providers to maintain skill-based competence for intrathecal access procedures. Methods: A prospective QI design using intrathecal access simulation to assess, educate, and evaluate skill competency. Simulation was used as a strategy to promote patient safety and standardize practice patterns. Pretest and posttest methodology using paired t tests were performed to assess anxiety, confidence, and knowledge. Results: Fourteen pediatric providers participated in this QI project. There was a statistically significant improvement in confidence measuring intracranial pressure (ICP; t = −2.92, P = .013), performance-related overall anxiety (t = −2.132, P = .05) and administering intrathecal chemotherapy (t = −2.144, P = .053). Fifty percent of participants missed a medication error demonstrating confirmation bias. Conclusion: This simulation strategy resulted in improved confidence in measuring ICP, performance-rel...
Radiochemotherapy in the Management of Pancreatic Cancer—Part II: Use in Adjuvant and Locally Unresectable Settings

Inherently, treating pancreatic adenocarcinoma with chemotherapy is limited by the marginal sensitivity of this tumor to available drugs and drug combinations. For radiotherapy, a similar therapeutic insensitivity is adversely combined with a compromised ability to escalate biologic dose within relevant target volumes because of an intertwining and surrounding matrix of dose-limiting critical normal organs and tissues. The need for effective adjuvant therapy has been intensified by an increase in the safety, applicability, and availability of surgical resection even though such resections remain largely inadequate for producing long-term disease-free survival. The need for improved treatments for locally unresectable tumors remains self-evident based on limited prognosis and the frequency of this presentation. Studies in both domains have attempted to incorporate technical advances in radiotherapy planning and delivery (3-dimensional conformal, intensity modulation) as well as the systemic promise and radiosensitizing properties of gemcitabine-based approaches. The challenges of clinical research are well reflected by the controversies resulting from available studies and the difficulties in successfully designing and executing future trials.
Symbolic execution of acyclic workflow graphs

We propose a new technique to analyze the control-flow, i.e., the workflow graph of a business process model, which we call symbolic execution. We consider acyclic workflow graphs that may contain inclusive OR gateways and define a symbolic execution for them that runs in quadratic time. The result allows us to decide in quadratic time, for any pair of control-flow edges or tasks of the workflow graph, whether they are sometimes, never, or always reached concurrently. This has different applications in finding control- and data-flow errors. In particular, we show how to decide soundness of an acyclic workflow graph with inclusive OR gateways in quadratic time. Moreover, we show that symbolic execution provides diagnostic information that allows the user to efficiently deal with spurious errors that arise due to over-approximation of the data-based decisions in the process.
Thermal‐Mechanical History and the Strength of Magnesium Oxide Single Crystals: II, Etch Pit and Electron Transmission Studies

Mechanical tests show that the room-temperature flow strength of magnesia single crystals varies with heat treatment. Flow strength depends on the size, density, and distribution of precipitate particles which inhibit the motion of dislocations. The present paper describes optical and electron transmission microscope evidence for a precipitation reaction in magnesium oxide. The observations correlate fairly well with mechanical test data. Mechanical tests also show that mobile dislocations are locked by heating above 600°C. The room-temperature yield strength increases with time and temperature particularly when the aging temperature exceeds 1000°C. Studies to determine the nature of this locking mechanism are described. Etch pit studies show that dislocations aged above 600°C etch at a slower rate than fresh dislocations. This corresponds precisely with the change in mechanical behavior and both effects are attributed to impurity diffusion to dislocation lines. Electron transmission studies indicate a redistribution of point defects, left by moving dislocations, above 600°C. Eventually these result in a change in dislocation configuration which is considered responsible for the strong locking observed above 1000°C.
Application of a hierarchical framework for assessing environmental impacts of dam operation: Changes in streamflow, bed mobility and recruitment of riparian trees in a western North American river

River systems have been altered worldwide by dams and diversions, resulting in a broad array of environmental impacts. The use of a process-based, hierarchical framework for assessing environmental impacts of dams is explored here in terms of a case study of the Kootenai River, western North America. The goal of the case study is to isolate and quantify the relative effects of multiple dams and other river management activities within the study area and to inform potential restoration strategies. In our analysis, first-order impacts describe broad changes in hydrology (determined from local stream gages), secondorder impacts quantify resultant changes in channel hydraulics and bed mobility (predicted from a 1D flow model), and third-order impacts describe consequences for recruitment of riparian trees (recruitment box analysis). The study area is a 233 km reach bounded by two dams (Libby and Corra Linn). Different times of dam emplacement (1974 and 1938, respectively) allow separation of their relative impacts. Results show significant changes in 1) the timing, magnitude, frequency, duration and rate of change of flows, 2) the spatial and temporal patterns of daily stage fluctuation, unit stream power, shear stress, and bed mobility, and 3) the potential for cottonwood recruitment (Populus spp.). We find that Libby Dam is responsible for the majority of first and second-order impacts, but that both dams diminish cottonwood recruitment; operation of Corra Linn adversely affects recruitment in the lower portion of the study reach by increasing stage recession rates during the seedling establishment period, while operation of Libby Dam affects recruitment in the middle and upper portions of the study reach by changing the timing, magnitude, and duration of flow. We also find that recent experimental flow releases initiated in the 1990s to stimulate recovery of endangered native fish may have fortuitous positive effects on cottonwood recruitment potential in the lower portion of the river. This case study demonstrates how a process-based, hierarchical framework can be used for quantifying environmental impacts of dam operation over space and time, and provides an approach for evaluating alternative management strategies. Published by Elsevier Ltd.
Pulmonary Adenocarcinoma: The Expanding Spectrum of Histologic Variants

Abstract Pulmonary adenocarcinoma is one of the most common types of lung cancer. Traditionally, adenocarcinomas have been divided based on their degree of resemblance to their parent tissues into 3 histopathologic types: well, moderately, and poorly differentiated. In the majority of cases, this schema is sufficient to categorize these lung tumors. However, there is a considerable group of tumors in which the histology is not that of the classic gland-forming neoplasm. Thus, although the terminology of adenocarcinoma is applied in such cases, the histopathologic features are different from those of the more conventional variants. The current review addresses these unusual variants and the importance of recognizing and properly categorizing them to avoid unnecessary additional workup or possible misdiagnosis.
The Decline of the Beluga Sturgeon: A Case Study about Fisheries Management

Beluga sturgeon (Huso huso) have inhabited the earth for more than 100 million years. During the past 20 years their numbers have declined by 90%, plummeting to the lowest population sizes ever recorded. This drastic decline has created much controversy as to whether harvest and trade of this species should continue. The situation is further complicated by management that varies among countries sharing the same resources, international trade, and altered ecological conditions that have decreased survival and natural reproduction. In January 2006, the Convention on Interna- tional Trade in Endangered Species (CITES) suspended the trading of all wild beluga sturgeon caviar from the Caspian Sea. A year later, CITES re-opened the trade of beluga sturgeon, despite much pressure from researchers. Opening and closing beluga sturgeon trade impacts the market and affects many parties, including fishers, consumers, and managers. After completing this case, students will have a better understanding of the complex process of managing shared natural resources, specifically dealing with beluga sturgeon populations in the Caspian Sea region. This case will also allow students to expand their critical thinking skills for decision making on a global, ecological issue while learning about a complicated problem involving many opinions, countries, and livelihoods.
Adjusting to Globalization: Japan and the Mobility of Asian Technical Talent

The purpose of this paper is to understand the transition that Japan must make to regain its global economic competitiveness. It examines the significance of foreign technical talent to the Japanese high technology sector, specifically, the information and communications technology (ICT) industry. Japan is the second largest ICT market in the world. And since ICT services such as software development is labor intensive, under unfavorable demographic developments, Japan is likely to confront shortages of talent and thus competitive challenges. Given that both the Chinese and Indian economies and ICT sectors are growing rapidly, albeit differently, my hypothesis is that there will be greater mobility of technical talent to Japan and by extension greater engagement of Japanese businesses with Asian ICT firms. This study aims to shed light on why and how Japan must adjust to globalization by bringing out the patterns of talent movement from Asian countries to Japan.
The Metaphysics of Espronceda’s Romanticism in El estudiante de Salamanca

El estudiante de Salamanca, written from 1836 to 1839 in successive drafts, broaches the subject of metaphysics by accompanying its main character beyond the threshold of death. Its Romantic vision subverts traditional expectations. This study illuminates how clashes between figures that represent opposing orders nullify each other as a repeated pattern in the four-part poem. The Bourdieuian concepts of doxa, the habitus, and symbolic capital prove essential in clarifying the Romantic poet’s grappling with the existing order of his time as well as with the emergent order of liberalism. These constructs from Bourdieu’s theory of social practice also serve to place the work on a continuum of metaphysical representations comprising the baroque, deism, and the Gothic. An anti-hero without respect for doxa, who squanders symbolic capital, perishes in the grasp of the habitus, exemplifying the problematic structures of feeling of Spanish Romanticism towards Catholicism, market capitalism, and the exchange economy.
Leading School-Wide Improvement in Low-Performing Schools Facing Conditions of Accountability: Key Actions and Considerations.

Purpose – The purpose of this paper is to advance a framework that identifies three key domains of work and a set of more nuanced considerations and actions within each domain for school leaders seeking to improve school-wide student learning in low-performing schools facing conditions of accountability. Design/methodology/approach – Review of literature. Findings – Drawing from the work of Robinson et al. (2008), the authors identify and discuss a set of nuanced considerations and actions for school leaders seeking to improve school-wide student learning in low-performing schools facing conditions of accountability. These considerations and actions fall into three broad domains of leader work: first, goal setting and planning for goal achievement; second, promoting and participating in teacher learning; and third, planning, coordinating, and evaluating teaching and curriculum. Practical implications – This paper generates implications for school leaders, and school leader developers, school districts, an...
Purification of adenylosuccinate lyase from rat skeletal muscle by a novel affinity column. Stabilization of the enzyme, and effects of anions and fluoro analogues of the substrate.

Abstract Adenylosuccinate lyase from rat skeletal muscle was purified to apparent homogeneity by a combination of ion-exchange chromatography and affinity chromatography on agarose containing covalently bound adenylophosphonopropionate. The purified enzyme is stable when stored in 20% glycerol at -70 degrees C, and can be thawed and re-frozen with minimal loss of activity. Adenylosuccinate lyase has a specific activity of 11 mumol/min per mg of protein at 25 degrees C. Its subunit Mr is 52,000, by SDS/polyacrylamide-gel electrophoresis, and its apparent native Mr is approx. 200,000, by gel filtration. The purified enzyme has Km values for adenylosuccinate and 4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR) of 1.5 microM and approximately 1 microM respectively, in Hepes/KOH buffer, pH 7.4. Several monoanions and dianions activate the enzyme at low concentration; several of these inhibit the enzyme at high concentrations. Fluoro analogues of adenylosuccinate and SAICAR were synthesized by using highly purified adenylosuccinate synthase and SAICAR synthase respectively, and erythro-beta-fluoroaspartate in place of aspartate. Both analogues are competitive inhibitors of adenylosuccinate lyase in both of the reactions catalysed by the enzyme, with Ki values well below the Km values for the two substrates.
Metallic materials for 3D printing

Three-dimensional (3D) printing of metallic materials involves the layerwise consolidation of feedstock materials in the form of powder, wire, or sheet using various energy sources to form complex shapes. The past two decades have witnessed significant advances in the field, in terms of both technologies and materials for metal 3D printing. This has led to widespread exploration and adoption of the technologies across industry, academia, and R&D organizations. This article presents an overview of the field of metal 3D printing. A brief history of metal 3D printing is followed by an overview of metal 3D printing methods and metallic material systems used in these methods. Microstructure and properties, and their relationship to process parameters are discussed next, followed by current challenges and qualification issues. The article concludes with future trends and a brief description of the invited articles included in this special issue.
Coulomb Correction in Nuclear β Decay: Elementary-Particle Treatment

The "elementary-particle" treatment of nuclear $\ensuremath{\beta}$ decay is extended to include the effects of final-state Coulomb interactions. The resulting formalism is valid for both allowed and forbidden decays. The Coulomb correction in allowed transitions is considered in detail and compared with the usual impulse-approximation calculation. The spectrum shape factor for the transition ${\mathrm{B}}^{12}\ensuremath{\rightarrow}{\mathrm{C}}^{12}+{e}^{\ensuremath{-}}+{\overline{\ensuremath{\nu}}}_{e}$ is evaluated as an example.
Reducing Hospital Readmissions Through Preferred Networks Of Skilled Nursing Facilities

Establishing preferred provider networks of skilled nursing facilities (SNFs) is one approach hospital administrators are using to reduce excess thirty-day readmissions and avoid Medicare penalties or to reduce beneficiaries’ costs as part of value-based payment models. However, hospitals are also required to provide patients at discharge with a list of Medicare-eligible providers and cannot explicitly restrict patient choice. This requirement complicates the development of a SNF network. Furthermore, there is little evidence about the effectiveness of network development in reducing readmission rates. We used a concurrent mixed-methods approach, combining Medicare claims data for the period 2009–13 with qualitative data gathered from interviews during site visits to hospitals in eight US markets in March–October 2015, to examine changes in rehospitalization rates and differences in practices between hospitals that did and did not develop formal SNF networks. Four hospitals had developed formal SNF networ...
Alloy Design Criteria for Solid Metal Dealloying of Thin Films

Liquid metal dealloying is a promising route for making metal nanocomposites with a wide range of microstructure morphologies. However, it is not well suited for synthesizing nanocomposites in thin-film form. We propose a new route to fabricating fully dense nanocomposite thin films by dealloying a binary parent alloy in a unary solid metal solvent. We fabricated and tested three thin-film diffusion couples to understand the alloy design criteria for synthesizing dealloyed thin films free of cracks and voids. We find that the best-quality dealloyed thin films may be obtained from alloys that do not undergo large volume changes upon dealloying and that exhibit minimal net vacancy flux during interdiffusion.
Social information cascades influence the formation of mixed-species foraging aggregations of ant-following birds in the Neotropics

Animals frequently make decisions based on social information obtained from other animals, which can influence interspecific interactions and affect individual fitness. For example, animals eavesdrop on other animals to find profitable food resources, yet the types of cues they use and how these cues influence decisions to approach a resource remain poorly understood. In tropical systems, arthropods inadvertently flushed by army ant, Eciton burchellii, swarms are an important food resource for many bird species, which form mixed-species foraging aggregations at swarms. Competition at swarms is intense and birds vocalize to defend foraging areas, inadvertently producing acoustic social information about the swarm's location. Eavesdropping birds may use these acoustic cues, which provide information about the bird aggregation (i.e. species participating in the aggregation, the size of the aggregation and/or diversity of the aggregation) to assess potential benefits (food resources) and costs (competition for food) of joining an aggregation. To test this hypothesis, we used an acoustic playback experiment to simulate aggregations of birds foraging at ant swarms and we measured community-wide and guild-specific responses of forest birds to playbacks. We included three types of acoustic social information in playbacks that potentially interact to affect an eavesdropping bird's probability of attraction to a swarm: (1) aggregation size, (2) aggregation species richness and (3) degree of specialization on ant swarms for food of birds vocalizing in the aggregation (hereafter ‘dependency’). Using Bayesian generalized linear mixed models, we found that playbacks of obligate ant-following species elicited greater community-wide responses (i.e. attracted more individuals and species) to simulated aggregations compared to playbacks of other, less dependent guilds. We also found that interactions between dependency, species richness and aggregation size influenced the overall community response to playbacks and that species from one guild generally responded to the guild above them (i.e. from less to more specialized). Our results suggest that species evaluate multiple types of acoustic cues representing the costs and benefits of foraging in a mixed-species aggregation at a swarm. We hypothesize that species change from information receivers to information producers upon joining a swarm, ultimately producing an information cascade that further affects the dynamics of feeding aggregations at swarms.
Wavelength variation of a standing wave along a vertical spring

Hand-driven resonance can be observed readily in a number of mechanical systems including thin boards, rods, strings, and springs. In order to show such behavior in the vertical spring pictured in Fig. 1, a section of spring is grasped at a location about one meter from its free end and driven by small, circular motions of the hand. At driving frequencies of a few hertz, a dramatic standing wave is generated. One of the fascinating features of this particular standing wave is that its wavelength varies along the length of the spring.
Abstract 3299: High-throughput combinatorial CRISPR-Cas9 gene knockout reveals most genetic interactions are context dependent

Genetic interactions, in particular negative or "synthetic-lethal" interactions for which simultaneous disruption of two genes causes cell killing, have implications for therapeutic development as has been demonstrated by the clinical success of PARP inhibitors specifically for tumors with loss-of-function mutations in BRCA1/2. However, further applications of synthetic-lethal cancer therapy have been limited by poor understanding of the important genetic interactions in a cancer cell, and how these vary from one cancer type to another or from patient to patient. To enable systematic mapping of these genetic interaction networks, we recently developed a CRISPR-Cas9 screening methodology for knocking out single and pairs of genes in high throughput. Critical to this method is the precise determination of single-gene knockout effects, which is accomplished by serial measurement of the relative changes in gRNAs at days 3, 14, 21 and 28 post-transduction. To robustly quantify gene fitness and genetic interactions we developed a novel computational analysis framework that integrates all samples across the multiple days of the experiment; with said method we achieve Pearson correlation of 0.95 or greater between biologic replicates in the same cell line (p Citation Format: John Paul Shen, Dongxin Zhao, Brenton Munson, Amanda Birmingham, Roman Sasik, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Alex Beckett, Kyle Salinas Sanchez, Prashant Mali, Trey Ideker. High-throughput combinatorial CRISPR-Cas9 gene knockout reveals most genetic interactions are context dependent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3299.
Functional Sleep Disorders

Sleep-related disorders are common, and when left untreated, they can negatively impact health, cognitive development and learning, behavior, and emotional regulation. This chapter will focus on sleep disorders with no known primary organic trigger, which thus can be defined as falling within the spectrum of functional disorders. Fortunately, these disorders are amenable to adjustment of patients’ behavior and/or cognition. Patients with sleep disorders are often treated by specialists who deal with pulmonary disease, and many of the therapies employed in the treatment of such sleep disorders are the same as those for functional respiratory disorders. Sleep-related disorders that are treated primarily by medical or surgical therapies such as sleep-disordered breathing (SDB), narcolepsy, idiopathic hypersomnolence, and restless legs syndrome will not be discussed. However, application of positive airway pressure (PAP) therapy for SDB is demanding, and many patients have difficulties with its application. Thus, management of the functional issues associated with application of this therapy is discussed.
A global inventory of nitric oxide emissions from soils

Over 60 published papers reporting field measurements of emissions of nitric oxide (NO) from soil are reviewed, and over 100 annual estimates of NO emissions were made for various types of ecosystems, including agricultural fields. These data were stratified by biome and the mean of each stratum was multiplied by an estimate of the biome area. A few strata were identified as clearly having low NO emissions: montane forests, swamps and marshes, tundra, and temperate forests that are not heavily affected by N deposition. The largest emissions were observed in tropical savanna/woodland, chaparral, and cultivated agriculture, but variation in NO emissions within these strata was also large. Although the stratification scheme fails to partition this within-stratum variation, it does clearly identify these biomes as globally important sources of NO and as areas where more research is needed to investigate within-biome variation in NO emissions. It is too early to tell whether differences in NO emissions between temperate and tropical agriculture are significant, but it is clear that agriculture is an important source of NO and that management practices affect NO emissions. The best current estimate of the global soil source of NO is 21 Tg N yr-1. Adsorption of NOx onto plant canopy surfaces may reduce emissions to the atmosphere to as low as 13 Tg N yr-1, although the absorption effect is probably smaller than this. An error term for the global estimate is difficult to determine, but it is at least ±4 and perhaps as large at ±10 Tg N yr-1. Hence, only modest progress has been made in narrowing uncertainties in the estimate of the global soil source of NO, although some published lower estimates appear unlikely. This inventory reconfirms that the soil source of NO is similar in magnitude to fossil fuel emissions of NOx. Further narrowing of the uncertainty of the estimate of global soil NO emissions will require more sophisticated and carefully chosen stratification schemes to address variation within biomes based on soil fertility, soil texture, climate, and management and will require linking this type of inventory and stratification with mechanistic models.
Chronic Pain Explained

Pains that persist long after damaged tissue hasrecovered remain a perplexing phenomenon. Theseso-called chronic pains serve no useful function foran organism and, given its disabling effects, mighteven be considered maladaptive. However, a remarkablesimilarity exists between the neural bases thatunderlie the hallmark symptoms of chronic pain andthose that subserve learning and memory. Bothphenomena, wind-up in the pain literature andlong-term potentiation (LTP) in the learning andmemory literature, are forms of neuroplasticity inwhich increased neural activity leads to a longlasting increase in the excitability of neuronsthrough structural modifications at pre- andpost-synaptic sites. Moreover, the synapticmodifications of wind-up and LTP share a commonmechanism: a glutamate N-methyl-D-aspartate(NMDA) receptor interaction that initiates a calciummediated biochemical cascade that ultimately enhancessignal processing at theα-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor. This paper arguesthat chronic pain, which has no adaptive value, canbe accounted for in terms of the highly adaptivephenomenon of activity-dependent neural plasticity;hence, some cases of chronic pain can beconceptualized as a memory trace in spinal neurons.
Adaptive Bayesian Design with Penalty Based on Toxicity-Efficacy Response

The penalized local D-optimal design is introduced by Dragalin and Fedorov (J. Stat. Plan. Inference 136:1800–1823, 2006). We extend the method to the Bayesian realm for the bivariate Gumbel model. Then we conduct a simulation study to compare our method with the trade-off methods of Thall and Cook (Biometrics 60:684–693, 2004). Various measures are employed to present a thorough understanding of both the methods. Our method is more favorable in terms of consistency across simulations and information gain.
How the Web helps people turn ideas into code

Publisher Summary This chapter investigates the role of online resources in building software. It focuses specifically on how programmers—an exemplar form of knowledge workers—opportunistically interleave Web foraging, learning, and writing code. To understand this, it presents both how programmers work in the lab and analyzes Web search logs of programming resources. The lab provides rich, detailed information and context about how programmers work; online studies offer a naturalistic setting and the advantages of scale. It was found that programmers engage in just-in-time learning of new skills and approaches, clarify and extend their existing knowledge, and remind themselves of details deemed not worth remembering. The results also suggest that queries for different purposes have different styles and durations. These results contribute to a theory of online resource usage in programming and suggest opportunities for tools to facilitate online knowledge work. Additionally, with ready access to good examples, programmers may need less training in languages, frameworks, and libraries and greater skill in formulating and breaking apart complex problems. It may be that programming is becoming less about knowing how to do something and more about knowing how to ask the right questions.
Electrolyte Effects on the Transport of Cationic Amino Acids

I should like to begin by expressing my appreciation of the presentation just made by Dr. Eddy. Through several years he has carefully focussed his attention on the smaller contribution made by the K+ gradient, along with the larger one made by Na+ gradient. His new results suggest that the K+ gradient may exert a much larger energizing effect when the ATP levels have not been depressed. As I heard the ion-gradient hypothesis so beautifully and challengingly explained, I thought to myself, this corresponds well to the possibility that Riggs and I saw in 1952 as a basis for the Na+ for K+ exchange accompanying glycine uptake by the Ehrlich cell. We had results even then that might have justified our limiting our consideration to the sodium ion (see Fig. 1) as we developed the alkali-metal ion-gradient hypothesis, but there was accompanying evidence urging us to retain interest in the potassium ion. As a personal note and in a lighter vein I may mention a subjective reason: My distinguished mentor, Baird Hastings, has long had firm convictions about potassium, and he would never have forgiven me if we had overlooked the role of that ion. I must admit that from 1961 to about 1965 I came to be slightly rueful that we had not got the alternative forms of the alkali-metal gradient hypothesis into the titles and abstracts of our papers, as well as into the text. The subsequent development of the subject has, however, I am sure been rewarding to everyone.
Self and Other in Feminist Thought

Feminist thought has confronted the question of duties to others in diverse ways, but within this pluralism some common themes prevail. Feminist thinking in almost all of its manifestations has offered a critique of mainstream thought [5]. In respect to duties to others, feminists challenge certain dominant assumptions in contemporary ethics in regard to the self and the self’s relationship to others. Feminists have not accepted rationalistic, individualistic, atomistic, and disembodied accounts of human persons. Nor have traditional modes of ethical and moral reasoning been immune from criticism.
The Impact of Social Deprivation on Pediatric PROMIS Health Scores After Upper Extremity Fracture.

Purpose Although social deprivation is acknowledged to influence physical and mental health in adults, it is unclear if and how social deprivation influences perceived health in children. This study was conducted to evaluate the impact of social deprivation on Patient-Reported Outcomes Measurement Information System (PROMIS) scores in children presenting for treatment of upper extremity fractures. Methods This cross-sectional evaluation analyzed data from 975 new pediatric patients (8–17 years old) with upper extremity fractures presenting to a tertiary orthopedic center between June 1, 2016, and June 1, 2017. They completed self-administered PROMIS Computer Adaptive Tests (CATs). The Area Deprivation Index was used to quantify social deprivation. Bivariate statistical analysis determined the effect of disparate area deprivation (based on most and least deprived national quartiles) for the entire population. Results A total of 327 children (34%) lived in areas categorized as the most socially deprived quartile of the United States, whereas 202 (21%) arrived from homes in the least socially deprived quartile. Children in the most deprived quartile had significantly worse mean PROMIS Upper Extremity Function, Mobility, Pain Interference, and Peer Relations scores than those in the least deprived quartile. Significantly more children from the most socially deprived areas were black. Patient age, sex, and fracture type were not significantly different between patients from the least and the most socially deprived quartiles. Conclusions Children living in areas of greatest social deprivation report worse Upper Extremity Function, Mobility, Pain Interference, and Peer Relations scores on self-administered PROMIS CATs than children from areas of least social deprivation at presentation for care of upper extremity fractures. The impact of social deprivation on perceived health and function is evident before adulthood and, therefore, interventions to mitigate this effect should be offered to children as well as adults. Type of study/level of evidence Prognostic II.
Strength Training Effects on Muscle Forces and Contributions to Whole-Body Movement in Cerebral Palsy

Strength training is often prescribed for children with cerebral palsy (CP); however, links between strength gains and mobility are unclear. Nine children (age 14 ± 3 years; GMFCS I-III) with spast...
Arterial embolism in a patient with pulmonary embolism and patent foramen ovale.

Paradoxical embolization is an uncommon but devastating complication of pulmonary embolism and continues to be frequently missed. Although the prevalence of patent foramen ovale is 25% to 30%, the ...
A New Single-Switch Structure of a DC–DC Converter With Wide Conversion Ratio for Fuel Cell Vehicles: Analysis and Development

In this paper, a new single-switch transformerless boost dc–dc converter is proposed for fuel cell vehicles. The developed topology utilizes a switched-capacitor multiplier and an integrated LC $^{2}D$ output network in order to enhance the voltage gain of the converter and reduce the voltage stress on the power switch. In addition, the proposed converter has a wide voltage gain range to suit the wide voltage swings of the fuel cell. The operating principles and the steady-state analyses of the proposed converter when it operates in continuous conduction mode (CCM) and discontinuous conduction mode (DCM) are illustrated in this paper. Additionally, the dynamic modeling and the compensator design for the developed converter are discussed. A scaled-down 800-V, 1.3-kW experimental prototype was built using a gallium nitride (GaN) transistor and silicon carbide (SiC) diodes to validate the theoretical analyses of the proposed converter.
Best of Both Worlds: Body Image and Satisfaction of a Sample of Black-Japanese Biracial Individuals

(1997). Best of Both Worlds: Body Image and Satisfaction of a Sample of Black-Japanese Biracial Individuals. Amerasia Journal: Vol. 23, No. 1, pp. 87-98.
Leininger’s Theory of Culture Care Diversity and Universality: An Overview With a Historical Retrospective and a View Toward the Future:

An historical overview of Leininger's Theory of Culture Care Diversity and Universality also known as the Culture Care Theory (CCT) and evolution of the Sunrise Enabler are presented along with descriptions of the theory purpose, goal, tenets, basic assumptions, major core constructs, and orientational definitions. Recent articles, books, and book chapters provide relevant exemplars to enhance scholarly understanding and application of theory constructs. Proposed future directions encompass using the CCT to guide research of discovery and translational research projects for evidenced-based nursing practice; develop nursing courses and curricula to prepare culturally competent nurses; guide future culturally competent administrative and leadership policies and procedures; inform public policy related to cultural diversity and underserved populations; promote grant writing initiatives to enhance cultural diversity in hiring nursing staff, supervisors, and faculty; and promote admission of nursing students from underserved and/or diverse backgrounds.
An Ultra Low-Power Neuromorphic Bandpass Filter for Autonomous Cars

An ultra low power neuromorphic bandpass filter (BPF) for dedicated short range communication system is proposed. The filter is designed for an intermediate frequency receiver for a passband of 75 MHz with 37.5 MHz center frequency. In an effort to improve the filter performance without compromising power consumption; a standard R m -C BPF structure is incorporated within the modified Izhikevich neuron to design the neuromorphic bandpass filter. Implemented in 45 nm CMOS technology, the proposed bandpass filter consumes 100.8 nW at a supply voltage of 0.5 V. The neuromorphic bandpass filter demonstrates excellent figure-of-merit (FOM) of -181.5 dB for a spurious free dynamic range of 27.1 dBm.
Higher Dimension Quantum Entanglement Generators

Quantum information processing and communication techniques rely heavily upon entangled quantum states, and this dependence motivates the development of methods and systems to generate entanglement. Much research has been dedicated to state preparation for radix-2 qubits, and due to the pursuit of entangled states, the Bell state generator and its generalized forms where the number of entangled qubits is greater than two have been defined. In this work, we move beyond radix-2 and propose techniques for quantum state entanglement in high-dimensional systems through the generalization of the binary bipartite entanglement states. These higher-radix quantum informatic systems are composed of n quantum digits, or qudits, that are each mathematically characterized as elements of an r-dimensioned Hilbert vector space where r > 2. Consequently, the wave function is a time-dependent state vector of dimension rn. The generalization of the binary controlled-NOT to the controlled-modulo-addition gate, the concept of partial versus maximal entanglement, and architectures for generating higher-radix entangled states for the partial and maximal case are all presented.