cssi/SciSciGPT-SciSciNet huggingface dataset:
Systolic Hypertension : A Guide to Optimal Therapy

University of Pennsylvania Systolic hypertension is an independent risk factor for coronary artery disease, stroke, and end-stage renal disease. Nonpharmacological interventions for systolic hypertension include limitation of dietary sodium and alcohol intake along with weight reduction and aerobic exercise. Thiazide diuretics are first-line therapy for hypertension, especially when the goal is reduction of systolk blood pressure. Angiotensin-converting enzyme inhibitors and ongiotensin receptor blockers may delay or prevent the onset of diabetes. Calcium channel blockers effectively treat systolic hypertension and may be preferable in patients who require rate control or who have comorbid conditions such as Raynaud disease or migraine. Causes of refractory hypertension include renovascular disease, aldosteronism, pheochromocytoma, and thyroid dysfunction.
Whose Security is Important? Communicating Environmental Risk About Soil to a Diverse Audience

Scientists who do “policy-relevant science” typically are inexperienced and unproductive at communicating to the public and policy makers, the people who ultimately make the decisions that implement or ignore the science. Recent research in the field of cognitive science shows that humans are “motivated reasoners,” who effectively filter out information incompatible with their, and their community’s, value system. Many science education efforts are only partially effective, and some may in fact increase resistance among certain target groups. Science communication is not about improving the message, it is deeply understanding what makes people tick and what doesn’t. A handful of scientists, and a few rock stars like Bono of the band U2, either have deeply considered how to communicate or are inherently endowed with skills that can reach diverse and largely incompatible audiences. “Talking about soil like a rock star” does not imply swagger or unfettered enthusiasm; it implies that the speaker has a deep understanding of ways to connect to both the heart and mind of his or her audience.
Cpf1 Is A Versatile Tool for CRISPR Genome Editing Across Diverse Species of Cyanobacteria

Cyanobacteria are the ideal organisms for the production of a wide range of bioproducts as they can convert CO2 directly into the desired end product using solar energy. Unfortunately, the engineering of cyanobacteria to create efficient cell factories has been impaired by the cumbersome genetic tools that are currently available for these organisms; especially when trying to accumulate multiple modifications. We sought to construct an efficient and precise tool for generating numerous markerless modifications in cyanobacteria using CRISPR technology and the alternative nuclease, Cpf1. In this study we demonstrate rapid engineering of markerless knock-ins, knock-outs and point mutations in each of three model cyanobacteria; Synechococcus, Synechocystis and Anabaena. The markerless nature of cpf1 genome editing will allow for complex genome modification that was not possible with previously existing technology while facilitating the development of cyanobacteria as highly modified biofactories.
Infected Urachal Cyst.

A 19-month-old girl presented with abdominal pain. The initial examination was normal, but within 24 hours the umbilicus became protuberant and erythematous. The white-cell count was elevated. CT revealed a cystic mass extending from the umbilicus to the dome of the bladder.
Competing accounts of fiduciary obligation

Over the past several years, fiduciary scholars have developed several competing accounts of the fiduciary obligation. Studying these accounts leads to a more complete understanding of the fiduciary relationship and the obligations imposed on fiduciaries. In previous work, I presented an account of the fiduciary obligation as a duty by the fiduciary to adopt the principal’s ends. Under the “adopting” account, the fiduciary obligation can be viewed as a duty by the fiduciary to adopt the goals, objectives, or ends if the principal and act accordingly. This paper clarifies and extends the account, and it replies to objections raised by Professors Stephen Galoob and Ethan Leib. In contrast to the adopting account, Professors Galoob and Leib have articulated a “shaping” account of the fiduciary obligation. Under the shaping account, the fiduciary duty shapes the fiduciary’s deliberations vis-a-vis the principal and a fiduciary whose deliberations are not shaped in the way Professors Galoob and Leib describe does not comply with her fiduciary duty of loyalty. This paper maintains that the demands the shaping account places on a fiduciary are insufficient – they are inconsistent with fiduciary doctrine and with the custom and practice of fiduciaries. This paper also addresses objections posed by Professors Galoob and Leib, namely that the adopting account permits morally illicit ends and that it permits accidental compliance. Finally, this paper examines illustrations used by Professors Galoob and Leib to demonstrate that the adopting account is the more complete account of fiduciary obligation.
Metal Halide Perovskites: Processing, Interfaces, and Light Emitting Devices

We study the use of metal halide perovskites for light emitting diode (LED) applications. Through understanding of interface chemistry and improvements in film formation, we demonstrate green and red perovskite LEDs with external quantum efficiencies of approximately 10%.
A Scalable Synthesis Pathway to Nanoporous Metal Structures

A variety of nanoporous transition metals, Fe, Co, Au, Cu, and others, have been readily formed by a scalable, room-temperature synthesis process. Metal halide compounds are reacted with organolithium reductants in a nonpolar solvent to form metal/lithium halide nanocomposites. The lithium halide is then dissolved out of the nanocomposite with a common organic solvent, leaving behind a continuous, three-dimensional network of metal filaments that form a nanoporous structure. This approach is applicable to both noble metals (Cu, Au, Ag) and less-noble transition metals (Co, Fe, Ni). The microstructures of these nanoporous transition metals are tunable, as controlling the formation of the metal structure in the nanocomposite dictates the final metal structure. Microscopy studies and nitrogen adsorption analysis show these materials form pores ranging from 2 to 50 nm with specific surface areas from 1.0 m2/g to 160 m2/g. Our analysis also shows that pore size, pore volume, and filament size of the nanoporous...
Nucleotide excision repair.

Publisher Summary DNA damage is a common occurrence that compromises the functional integrity of DNA. It is not surprising then that cells have multiple mechanisms for coping with DNA damage, including those introduced by sunlight and other environmental agents. Nucleotide excision repair is a pluripotent pathway for the recognition and removal of a broad spectrum of DNA lesions. Nucleotide excision repair involves the removal of damaged DNA bases by dual incisions bracketing the damaged base, release of the damaged base in the form of 12–13 nucleotide-long oligomers in prokaryotes and 24– 32 nucleotide-long oligomers in eukaryotes followed by polymerase-mediated replacement of the excised nucleotides and sealing the repair patch with ligase. Structural work currently being carried out by numerous groups is expected to provide an understanding at the atomic level for both prokaryotic and eukaryotic excision nucleases, which will aid in designing further biochemical experiments to refine current models.
Evolutionary inferences about quantitative traits are affected by underlying genealogical discordance

Modern phylogenetic methods used to study how traits evolve often require a single species tree as input, and do not take underlying gene tree discordance into account. Such approaches may lead to errors in phylogenetic inference because of hemiplasy - the process by which single changes on discordant trees appear to be homoplastic when analyzed on a fixed species tree. Hemiplasy has been shown to affect inferences about discrete traits, but it is still unclear whether complications arise when quantitative traits are analyzed. In order to address this question and to characterize the effect of hemiplasy on traits controlled by a large number of loci, we present a multispecies coalescent model for quantitative traits evolving along a species tree. We demonstrate theoretically and through simulations that hemiplasy decreases the expected covariances in trait values between more closely related species relative to the covariances between more distantly related species. This effect leads to an overestimation of a trait's evolutionary rate parameter, to a decrease of the trait's phylogenetic signal, and to increased false positive rates in comparative methods such as the phylogenetic ANOVA. We also show that hemiplasy affects discrete, threshold traits that have an underlying continuous liability, leading to false inferences of convergent evolution. The number of loci controlling a quantitative trait appears to be irrelevant to the trends reported, for all analyses. Our results demonstrate that gene tree discordance and hemiplasy are a problem for all types of traits, across a wide range of methods. Our analyses also point to the conditions under which hemiplasy is most likely to be a factor, and suggest future approaches that may mitigate its effects.
Primary Care for the Transgender and Gender Nonconforming Patient.

All physicians are likely to encounter gender diverse patients. Some of these patients will require medically necessary surgical procedures. It is optimal for surgeons to collaborate with other providers who interact with this patient population. Primary care physicians initiate treatment with consultation from mental health professionals and refer to surgeons when necessary. Best practices consist of preventative care, hormone therapy induction when indicated, monitoring of all health parameters, and continuing care medically and postoperatively.
Observation of quantum beats in the 6D3/2-->5P1/2 transition in 85Rb.

Quantum beats due to the hyperfine interaction were observed in the 6${D}_{3/2}$\ensuremath{\rightarrow}5${P}_{1/2}$ transition in $^{85}\mathrm{Rb}$. Good agreement with theory was obtained, allowing determination of the values for the magnetic dipole (a=2.32\ifmmode\pm\else\textpm\fi{}0.06 MHz) and electric quadrupole (b=1.62\ifmmode\pm\else\textpm\fi{}0.06 MHz) hyperfine constants for the upper state.
OH A 2Sigma - X 2Pi (0,0) band rotational line emission rate factors

This paper presents the results of the emission-rate factor (g factor) calculations for the (0,0) band of the OH (A 2Sigma - X 2Pi) system, for the temperatures 200.0, 240.0, 296.0, 300.0, and 500.0 K, as well as for the individual g factors for each rotational line of the band. The derived g factor at 240 K for the entire band is 0.00055 + or - 0.00011 photon/sec. The g factor for the entire band was found to decrease with increasing temperature, but the difference in the change was less than 10 percent for the temperature range studied. The data on the individual rotational line g factors are valuable for future work on determining OH concentration profiles in the atmosphere, through the observation of the UV fluorescence in the OH (A 2Sigma - X 2Pi) (0,0) band using high-resolution spectrometers of a low-scattered-light design.
Affective responses to acute exercise : A test of opponent-process theory

Based on Solomon's Opponent-Process theory (1980), it was predicted that individuals involved in a regimen of regular aerobic exercise (active; n = 18) would respond to an acute bout of exercise with reduced negative and/or increased positive affect compared to nonactive counterparts (nonactive; n = 12). State Anxiety (SA), positive affect (PA), negative affect (NA), and self-reported fatigue were assessed immediately prior to, every 6 min during, and every 6 min following a 24 min bout of bicycle exercise performed at an RPE of 13 (+/- 1). As expected, no significant group differences occurred for RPE (M = 13.5 for nonactive, 13.2 for active). The active group did, however, exercise at a greater absolute workload than the nonactive group (261.0 +/- 22.4 W vs 200.0 +/- 19.98 W, respectively). Analyses indicated similar changes in SA and fatigue for both groups, with significant reductions in SA occurring at 6 min post-exercise and remaining below pre-exercise levels throughout the post-exercise period, while fatigue was reduced at 12, 18, and 24 min post-exercise. A significant Group x Time interaction occurred for affective valence (PA - NA; p < .01). Post hoc analyses indicated that for the active group, affect increased modestly (i.e., more PA, less NA) during exercise; this increase was sustained post-exercise. The nonactive group evidenced a sharp drop in affect (i.e., less PA, more NA) during exercise followed by a small post-exercise rise which did not return to pre-exercise levels. The results of the present study partially support the Opponent-Process model as an explanation for exercise-related affect. Although there was no differential anxiety response as a function of activity level as the model would predict, there was a differential response for affective valence in accordance with predictions.
Breaking out of the Bubble

clearly remember shivering while rapidly walking across the stage at graduation last May amidst relentless rain, bolts of lightning, and cracks of thunder. As I grasped my hard-earned diploma and smiled genuinely for the camera, I felt prepared to leave for Nicaragua as a Peace Corps volunteer in a few months. Much like my stormy graduation ceremony, my experience as a Peace Corps volunteer in Nicaragua has presented some challenges and is not exactly as I expected, but nonetheless, it has been interesting, and at the end of the day, I feel grateful to be here. This news and commentary is available in The Park Place Economist: http://digitalcommons.iwu.edu/parkplace/vol13/iss1/9
Skin Cancer Prevention Education: A National Survey of YMCAs

High skin cancer incidence and mortality rates have created a need for skin cancer prevention education. Children are an important target for this education, as overexposure to sun and sunburns at an early age have been linked to the development of skin cancer. This study identified the prevalence of skin cancer prevention education and the need for this education at YMCA swim classes. This study also assessed the feasibility of implementing Project SUNWISE, an existing skin cancer prevention curriculum, developed for YMCA swim classes. A 51-item survey was mailed to Aquatics Directors at all YMCAs with outdoor pools. Based on a 63% response rate (N = 208), only 28% of YMCAs thought the children in their swim classes were adequately protected from the sun, and only 28% offered skin protection or sun safety education in swim classes. Only 50% of YMCAs trained their swim instructors on skin cancer prevention. While 91% of YMCAs had one or more sun protection items near the pool (e.g., sunscreen, umbrella, covered area), 93% of YMCAs saw the need for additional protection. The majority of YMCAs (95%) were willing to incorporate a skin cancer prevention education curriculum, similar to Project SUNWISE, into their swim classes. This study emphasized the need for more skin cancer prevention education programs targeting children and examined the correlates of skin cancer prevention education at YMCAs. Geographic region, percent of possible sunshine, and ultraviolet radiation were significantly associated with the skin cancer prevention education program status at the YMCAs.
The Evolution from Lean to Obese State and the Influence of Modern Human Society

One of the paramount changes in human evolution was the development of large brain size with a tremendous impact on the nutritional behavior of our species. A larger brain demands more food intake to keep up with the need of the overall energy budget. This high demand for energy to maintain the brain metabolism forced early humans to move from a strictly vegetarian diet to more energy-rich diet. Changes in nutrient-rich energy diets evolving from an exclusively vegetarian to an omnivorous diet were among many evolutionary factors developed to maintain the high cost of a large human brain. Paleontological data indicates that fast brain evolution occurred with the appearance of Homo erectus 1.8 million years ago, which was related to critical changes in diet, body size, and foraging behavior. Then, the survival of more advanced humans depended on their ability to acquire energy for its daily use and storage, which was well balanced before the advent of modern humans. The energy balance of early humans is disrupted today by an excessive food intake, processed food, and an increase in sedentary life. Obesity pandemic has undoubtedly coincided with not only an increase in unhealthy eating habits but also with migratory movements of different ethnic communities to dissimilar environmental pressures. The heat producing of uncoupling proteins in mitochondria brown adipocyte tissue is believed to be a key driver behind the conquest of a variety of environments in mammals 65 million years ago. This ability to produce and maintain heat contributed to the evolution of mammals to explore and settle in uninhabitable territories throughout the planet by adjusting the thermoregulatory response to sharply different environments. It is also discussed in this chapter several early evolutionary hypotheses to explain the development of obesity and metabolic syndrome, the evolutionary changes from hominoids 20 million years ago to industrialized humans, and the effects on traits causing profound changes in the evolution of human nutritional requirements.
Application of solid electrolyte cells in ion pump and electrolyzer modes to promote catalytic reactions: An overview

Abstract Solid electrolyte cells can be operated in three basic modes: fuel cell, electrolyzer and ion pump. In the fuel cell mode, a fuel such as hydrogen, CO and light hydrocarbons is electrochemically oxidized to generate power. Electrolyzer and ion pump modes, however, need application of power from an external source in order to perform the desired tasks. In this article, we present a brief overview of the studies that use an oxygen ion conducting electrolyte for catalytic applications, with two specific examples from our own studies: use of a solid electrolyte cell in the ion pump mode for alkane oxidative dehydrogenation and in the electrolyzer mode for CO2 reduction. The solid electrolyte cell assembly used in these studies consists of a button cell containing yttria-stabilized zirconia solid oxide electrolyte, a modified strontium titanate (ST) catalyst as the working electrode, i.e., anode for the ODH reaction and cathode for the CO2 reduction reaction, and a lanthanum strontium manganite (LSM) catalyst as the counter electrode. Physical properties of the titanate materials were studied using XRD, conductivity measurement and temperature-programmed oxidation with CO2. Lanthanum doped strontium titanate (La0.2Sr0.8TiO3±δ), with or without Cl, was seen to have a higher electrical conductivity compared to un-doped strontium titanate (SrTiO3). Cl doping, however, was seen to improve the electrocatalytic activity for both ODH and CO2 reduction reactions, giving higher yields of ethylene and CO compared to Cl-free La0.2Sr0.8TiO3±δ. The comparison of the catalytic and electrocatalytic ODH reactions clearly pointed out that oxygen in ionic form was more selective to ethylene than molecular oxygen at similar conversion values.
If patients are the true north, patient-centeredness should guide research.

‘Patient-centered’ research has traditionally meant that researchers and clinicians design trials for the benefit of patients. By contrast, patients today are central to study design and reporting outcomes, and new research agendas recognize that patients can point the way to research questions and how to address them.
Integrated Analysis of Acetyl-CoA and Histone Modification via Mass Spectrometry to Investigate Metabolically Driven Acetylation

Acetylation is a highly abundant and dynamic post-translational modification (PTM) on histone proteins which, when present on chromatin-bound histones, facilitates the accessibility of DNA for gene transcription. The central metabolite, acetyl-CoA, is a substrate for acetyltransferases, which catalyze protein acetylation. Acetyl-CoA is an essential intermediate in diverse metabolic pathways, and cellular acetyl-CoA levels fluctuate according to extracellular nutrient availability and the metabolic state of the cell. The Michaelis constant (Km) of most histone acetyltransferases (HATs), which specifically target histone proteins, falls within the range of cellular acetyl-CoA concentrations. As a consequence, global levels of histone acetylation are often restricted by availability of acetyl-CoA. Such metabolic regulation of histone acetylation is important for cell proliferation, differentiation, and a variety of cellular functions. In cancer, numerous oncogenic signaling events hijack cellular metabolism, ultimately inducing an extensive rearrangement of the epigenetic state of the cell. Understanding metabolic control of the epigenome through histone acetylation is essential to illuminate the molecular mechanisms by which cells sense, adapt, and occasionally disengage nutrient fluctuations and environmental cues from gene expression. In particular, targeting metabolic regulators or even dietary interventions to impact acetyl-CoA availability and histone acetylation is a promising target in cancer therapy. Liquid chromatography coupled to mass spectrometry (LC-MS) is the most accurate methodology to quantify protein PTMs and metabolites. In this chapter, we present state-of-the-art protocols to analyze histone acetylation and acetyl-CoA. Histones are extracted and digested into short peptides (4-20 aa) prior to LC-MS. Acetyl-CoA is extracted from cells and analyzed using an analogous mass spectrometry-based procedure. Model systems can be fed with isotopically labeled substrates to investigate the metabolic preference for acetyl-CoA production and the metabolic dependence and turnover of histone acetylation. We also present an example of data integration to correlate changes in acetyl-CoA production with histone acetylation.
Impacts of Lock-off Time on Virtual Battery Model from Thermostatically Controlled Loads

We examine through simulation the impacts of lock-off time of thermostatically controlled loads (TCLs) on their aggregated flexibility, which are characterized as a virtual battery (VB). The VB model provides a simple and general way to quantify the aggregated flexibility of TCLs, but the physical device operation constraints such as lock-off time are not considered. Many TCLs should not be immediately switched on after being turned off, and this lock-off time constraint affects not only the availability of individual TCLs but also the aggregated flexibility from a group of TCLs. In this paper, impacts of lock-off time on the efficacy of VB models are studied through simulations using both artificial and practical signals with low and high frequency. It is found that with the lock-off time, the VB flexibility changes little when following slow signals, but is much reduced when following fast signals.
Kids These Days! Increasing delay of gratification ability over the past 50 years in children

Abstract Have children's ability to delay gratification decreased since the past? We analyze the past 50 years of data on the Marshmallow test of delay of gratification; where children must wait to get two preferred treats of their choosing; if they cannot wait, they only get one. Here we provide comprehensive evidence on whether children's ability to delay gratification has truly been decreasing, as theories of technology or a culture of instant gratification have predicted. Before analyzing the data, we polled 260 experts in cognitive development, 84% of who believed children are getting worse or are no different than those of the past. Contrary to this prediction, we show delay of gratification times are increasing over the past 50 years, corresponding to a fifth of a standard deviation increase in ability per decade. This mirrors the magnitude of secular gains in IQ seen over decades.
Master Classes with Menahem Pressler: by William Brown, Bloomington, IN, Indiana University Press, 2019, 224 pp., $45.00 (cloth), ISBN 978-0-253-04292-7

Written by William Brown, Professor Emeritus of Music and Provost Emeritus at Southwest Baptist University and a former student of Pressler, the 224-page volume is an easy read. The intended audien...
Analysis of monitoring data on drinking-water-borne endemic fluorosis from 2012-2016 in Inner Mongolia Autonomous Region

Objective To provide a basis for development of preventive measures through dynamical monitoring of the changing trends of endemic fluorosis areas and the prevalence of drinking-water-borne endemic fluorosis. Methods Using simple random sampling method, thirty monitoring villages in 11 counties of Inner Mongolia were selected as fixed monitoring villages from 2012 to 2016. The operation of water improvement projects was investigated, and water fluoride content was tested. Dental fluorosis of all 8 to 12-year-old students was diagnosed in the villages. Stratified random sampling by age was used to select 50 adults over 25-year-old in each monitoring village, and skeletal fluorosis was examined by X-ray. Results ①In 2012-2016, the water-improved rate of monitoring villages was 78.67% (118/150). Of all the water-improved projects, normal operating projects accounted for 92.98% (106/114). The exceeded rate of water fluoride in water-improved village was 31.36% (37/118). ②The detection rate of dental fluorosis and community fluorosis index (CFI) in children aged 8-12 of the villages with normal operating projects and qualified fluoride content were 20.88% (533/2 553) and 0.41; the detection rate of dental fluorosis and CFI of the villages with water-improved projects under abnormal operation or excessive fluoride were 49.53% (318/642) and 0.98; the detection rate of dental fluorosis and CFI of the villages without water-improved projects were 37.14% (442/1 190) and 0.76. ③The detection rate of X-ray skeletal fluorosis in adults of the villages with normal operating projects and qualified fluoride content was 18.97% (140/738); the detection rate of X-ray skeletal fluorosis in adults of the villages with water-improved projects under abnormal operation or excessive fluoride was 31.53% (111/352); the detection rate of X-ray in adults of the villages without water improvement projects was 31.17% (96/308). Conclusions Up to now, in Inner Mongolia Autonomous Region, some villages have not yet improved their drinking water quality, water fluoride content in some projects has exceeded the standard seriously, the prevalence of dental fluorosis in children aged 8-12 is very mild, there are still moderate and severe endemic areas. So the prevention and control measures of the water-improved defluoridation need to be further strengthened. Key words: Fluorosis, dental; Skeletal fluorosis; Monitoring
Competence-Aware Systems for Long-Term Autonomy

Recent years have seen a push towards deploying fully autonomous robots in large, complex domains such as autonomous driving, space exploration, and service robots. However, legal, ethical, or technical constraints have limited the extent of these systems' employable autonomy. In order to successfully achieve their intended goals, these systems must utilize assistance from humans to compensate for their limitations. For such systems to be successful over the course of a long-term deployment, they must both be cognizant of their own competence and have the ability to improve this competence over time in a safe way. Motivated by practical concerns faced in industry, this thesis provides a formal model for such a human-agent system to reason about its own competence and aims in future work to provide effective ways of safely improving the competence of the system over the course of its deployment.
Mate choice and the ‘opposite miss’ to Weber's law: proportional processing governs signal preferences in a treefrog

According to Weber's law, discrimination between stimuli is based upon the proportional difference (ΔI/I), not the absolute difference (ΔI), between their magnitudes (I). How such nonlinear processing of signal information by receivers impacts the effectiveness of communication and drives patterns of signal evolution remains poorly understood. To investigate whether female preferences for exaggerated sexual signals follow Weber's law, we tested females of Cope's grey treefrog, Hyla chrysoscelis, in two-alternative choice tests, in which we varied both the absolute (ΔI) and proportional (ΔI/I) differences in duration between two advertisement calls. Consistent with Weber's law, female preferences for longer signals increased as ΔI/I increased; however, preferences were negatively related to both ΔI and absolute signal duration (I). This so-called ‘opposite miss’ to Weber's law (i.e. poorer discrimination performance than predicted at high stimulus magnitudes) has potential to shape signal evolution in distinct ways that differ in the extent to which further signal exaggeration is favoured. Our results highlight that animals use a diversity of approaches to information coding in perception, including coding that is neither linear nor strictly proportional according to Weber's law, and that perceptual processes have the potential to impact an important selective pressure – female preferences – and shape animal communication.
Refinement of covalent EGFR inhibitor AZD9291 to eliminate off-target activity

Abstract Non-small-cell lung cancer (NSCLC) is a major disease that accounts for 85% of all lung cancer cases which claimed around 1.8 billion lives worldwide in 2020. Tyrosine kinase inhibitors (TKIs) that target EGFR have been used for the treatment of NSCLC, but often develop drug resistance, and the covalent inhibitor AZD9291 has been developed to tackle the problem of drug resistance mediated by the T790M EGFR mutation; however, there is a side effect of hyperglycemia that may be due to off-target activity. This study examines analogs of AZD9291 by chemical proteomics, identifying analogs that maintain T790M-EGFR engagement while showing reduced cross-reactivity with off-targets.
Efficient Non-Monte-Carlo Yield Estimation

Parametric yield estimation is a critical component in the Integrated Circuit design flow. We propose an efficient non-Monte-Carlo yield estimation method. Key is the use of sensitivity information efficiently obtained with the nominal circuit response. Based on Taylor expansion, the circuit performance can be approximated with a multivariate Gaussian distribution. Combining this with the circuit performance specifications, the yield can be estimated efficiently by repeatedly sampling from the obtained Gaussian distribution. Also proposed is an efficient method to identify impactful factors leading to yield loss (e.g., the most or least sensitive process variables; the tightest performance specifications) based on a multi-dimensional Venn Diagram. Circuit examples demonstrate that the proposed method can well estimate the yield while significantly reducing the number of circuit simulations. Moreover, the proposed yield analysis method can provide useful hints for yield enhancement.
Adenine base editing to treat progeria syndrome and extend the lifespan

Hutchinson-Gilford progeria syndrome (HGPS) is an exceedingly rare and hitherto incurable and fatal disease marked by accelerated aging simultaneously affecting a number of organs. Most cases of HGPS are caused by a single copy of a specific single-nucleotide mutation, c.C1824T, in the LMNA (lamin A) gene. Different mutations in LMNA are responsible for a variety of disorders affecting a variety of organs, including dilated cardiomyopathy, familial partial lipodystrophy, Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy, Charcot-Marie-Tooth disease, and restrictive dermopathy. The unique pathophysiology of HGPS arises from the distinctive nature of the c.C1824T mutation; despite being a synonymous mutation that does not directly change an amino acid in the lamin A protein, it nonetheless exerts a profound effect on the protein by creating a cryptic splice site that causes incorrect splicing of the LMNA mRNA transcript, resulting in production of a truncated form of lamin A termed progerin, which is constitutively farnesylated. The farnesylated protein inappropriately accumulates in cells and causes dysregulation of the nuclear lamina - a structure in which the normal lamin A protein is a key component - that results in cellular dysfunction, senescence, and death. Vascular smooth muscle cells (VSMCs) represent one of the cell types particularly affected by progerin, and cardiovascular complications are the typical cause of death of HGPS patients in their youth.
Deformable Registration for IGT

Intra-procedural imaging has led to dramatic advances in medicine by enabling interventions that were previously not feasible, reducing negative side effects, and improving clinical outcomes over a broad domain of clinical applications. The broad objective of image registration applied to image-guided procedures is to fuse the variety of information elements—such as pre- and intra-procedural images of different modalities, results of planning and post-processing—into an integrated and coherent intra-procedural view. Deformation of soft tissues over the course of the procedure or treatment is common, necessitating nonrigid or deformable registration approaches. In this chapter we aim to give a brief introduction to the field of deformable registration, introducing the main methodological concepts illustrated by the representative applications and approaches for NRR, and discuss some of the practical considerations and challenges related to validation of NRR methods. Following the brief overview of the components involved in a conventional deformable registration formulation, we next discuss in more detail two specific clinical research applications—neurosurgical planning and MR-guided prostate biopsy—that are enabled by deformable registration, focusing on the clinical motivation and various NRR approaches proposed in the context of those applications.
Two-Dimensional Mapping of the Electron Energy Distribution Function

In certain low pressure plasmas, the Non-Local Approximation (NLA) can simplify the solution of the Holtzman equation by describing the electron distribution function (EDF) as being spatially uniform in terms of total electron energy[1]. However, the NLA is limited to cases where the energy relaxation length is much larger than the discharge scale[2]. A “hybrid” approach uses the NLA to calculate the elastic part of the EDF and the space-dependent kinetic equation is used for the high energy part[3].
Texts in Ben Tey, Dogon of Béni village, Mali

Texts in Ben Tey, a Dogon language of Beni village near Douentza in eastern Mali. See also Heath, A grammar of Ben Tey. Both volumes are also archived online at Language Description Heritage Library.
Maximizing charging efficiency of lithium-ion and lead-acid batteries using optimal control theory

Optimal charging of stand-alone lead-acid and lithium-ion batteries is studied in this paper. The objective is to maximize the charging efficiency. In the lithium-ion case two scenarios are studied. First only electronic resistance is considered and in the next step the effect of polarization resistance is also included. By considering constant model parameters for the lithium-ion battery analytical solutions exists for both scenarios using Pontryagins minimum principle. In lead-acid chemistry the variation of total internal resistance with state of charge (SOC) is considerable and the optimal charging problem results in a set of two nonlinear differential equations with one initial and a final condition to be satisfied. This so called two point boundary value problem is solved numerically.
Comparison of human MM, NN, and MN blood group antigens.

Types MM, NN, and MN blood group substances have been isolated. All three materials are glycoproteins containing about 24% N-acetylneuraminic acid, 10% galactosamine, 5% glucosamine, and 14% galactose. The hexosamines appear to be N-acetylated. Amino acid analysis of the glycoproteins reveals them to be similar in composition and to be especially rich in serine and threonine. Treatment of the types MM and NN glycoproteins with alkali resulted in a decrease of serine and threonine, suggesting that these two amino acids may be involved in linkage to the oligosaccharide moieties. The native glycoproteins seem to be more resistant to alkali cleavage of the carbohydrate-protein linkage than the sialic acid-free glycoproteins. All three of the glycoproteins seem to be equally susceptible to the action of neuraminidase.
The endogenous opioid spinorphin blocks fMet-Leu-Phe-induced neutrophil chemotaxis by acting as a specific antagonist at the N-formylpeptide receptor subtype FPR.

Spinorphin is an endogenous heptapeptide (leucylvalylvalyltyrosylprolyltryptophylthreonine), first isolated from bovine spinal cord, whose sequence matches a conserved region of β-hemoglobin. Also referred to as LVV-hemorphin-4 and a member of the nonclassical opioid hemorphin family, spinorphin inhibits enkephalin-degrading enzymes and is analgesic. Recently, spinorphin was reported to block neutrophil activation induced by the chemotactic N -formylpeptide N -formylmethionylleucylphenylalanine (fMLF), suggesting a potential role as an endogenous negative regulator of inflammation. Here we use both gain- and loss-of-function genetic tests to identify the specific mechanism of spinorphin action on neutrophils. Spinorphin induced calcium flux in normal mouse neutrophils, but was inactive in neutrophils from mice genetically deficient in the fMLF receptor subtype FPR ( N -formylpeptide receptor). Consistent with this, spinorphin induced calcium flux in human embryonic kidney 293 cells transfected with mouse FPR, but had no effect on cells expressing the closely related fMLF receptor subtype FPR2. Despite acting as a calcium-mobilizing agonist at FPR, spinorphin was a weak chemotactic agonist and effectively blocked neutrophil chemotaxis induced by fMLF at concentrations selective for FPR. Spinorphin did not affect mouse neutrophil chemotaxis induced by concentrations of fMLF that selectively activate FPR2. Thus, spinorphin blocks fMLF-induced neutrophil chemotaxis by acting as a specific antagonist at the fMLF receptor subtype FPR.
Parental Influence on Children's Socialization to Gender Roles.

In a society rife with gender stereotypes and biases, children regularly learn to adopt gender roles which are not always fair to both sexes. As children move through childhood and into adolescence, they are exposed to many factors which influence their attitudes and behaviors regarding gender roles. These attitudes and behaviors are generally learned first in the home and are then reinforced by the child's peers, school experience, and television viewing. However, the strongest influence on gender role development seems to occur within the family setting, with parents passing on, both overtly and covertly, their own beliefs about gender. This overview of the impact of parental influence on gender role development leads to the suggestion that an androgynous gender role orientation may be more beneficial to children than strict adherence to traditional gender roles.
Applying testability to reliability estimation

The purpose of the article is to implement the idea of using testability to estimate software reliability. The basic steps involve estimating testability, evaluating how well software was written, and assessing the effectiveness of testing. Results from these steps along with operational profiles are used to estimate software reliability. The paper describes an application of this method to evaluate the reliability of a real software system of about 6000 lines of executable code and discusses the results of such an estimation. The results are also compared with those obtained by using two reliability growth models.
Case Study in Ordinal Regression, Data Reduction, and Penalization

This case study is taken from Harrell et al.188 which described a World Health Organization study303 in which vital signs and a large number of clinical signs and symptoms were used to develop a predictive model for an ordinal response. This response consists of laboratory assessments of diagnosis and severity of illness related to pneumonia, meningitis, and sepsis. Much of the modeling strategy given in Chapter 4 was used to develop the model, with additional emphasis on penalized maximum likelihood estimation (Section 9.10). The following laboratory data are used in the response: cerebrospinal fluid (CSF) culture from a lumbar puncture (LP), blood culture (BC), arterial oxygen saturation (SaO 2, a measure of lung dysfunction), and chest X-ray (CXR). The sample consisted of 4552 infants aged 90 days or less.
DISTINCT GENOTYPE AND ANTIGENICITY AMONG GENOGROUP II SAPOVIRUSES

SaV, a pathogen of acute gastroenteritis, is divided into five genogroups, GI to GV. However, the relation between SaV antigenicity and genetic clusters is not fully understood. We have recently identified two GII SaV strains, Mc10 and C12, which are grouped into the same cluster based on the polymerase but are grouped into distinct clusters based on the capsid. To evaluate the difference in antigenicity between these two strains, VLP were expressed in mammalian cells. An antigen ELISA demonstrated for the first time that strains in the same GII SaV genogroup, but within different clusters, have distinct antigenicities.
PROOF OF THE FLUX EQUILIBRIUM RELATION.

A quantitative connection has been derived (3) between the measured E.M.F. of a living cell or tissue possessing electrical polarity and the velocity of cell oxidation, following Lund's (1) oxidation-reduction theory of bioelectric currents. The equations provide a consistent description of the major facts of continuous bioelectric currents and respiratory exchange. The respiratory process was schematized as follows :
Recommendations for Methods to Code Industry and Job Task in Routinely Collected Exposure Data

This article describes and recommends two coding methods that can improve the capture of exposure-relevant information in large occupational exposure databases. One of the methods can substantially improve the specificity of information captured by industry codes, and the second would improve the capture of information about job tasks in a standardized fashion, a capability almost entirely lacking in occupational health. The methods are not ideally designed for exposure assessment purposes, but their use would represent a substantial improvement over current practices. The methods have been well tested and can be adopted in their current form. Moreover, they are compatible with coding systems already in widespread use for economic, demographic, health, and other data, thus making exposure data coded with them amenable to valuable linkages. Large collections of routine exposure measurements are increasingly common, and the use of these coding methods will help improve the needed coding of precise informati...
The speed of adjustment to information: Evidence from the Chinese stock market

Abstract This paper examines the speed of price adjustment in Chinese A- and B-share stock markets. We use a VAR model to show that A-shares, which are owned primarily by domestic individual investors, adjust to information faster than do B-shares, which are owned primarily by foreign institutional investors. Our analysis of firm characteristics suggests that the speed of stock price adjustment for A-shares is related to earnings per share, while that for B-shares is related to firm size. We also find that A-shares react more quickly to bad news, while B-shares react more quickly to good news. The difference in the speed of adjustment between A- and B-shares decreased following the liberalization of financial policy in February 2001, which allowed domestic investors to purchase B-shares.
New Developments in Interferometry

This article is based on a series of talks presented by personnel of The Perkin-Elmer Corporation at a symposium held in September 1967 and thereafter brought up to date for inclusion in the APPLIED OPTICS feature discussing Interferometry vs Spectroscopy.
505: Does maternal BMI impact the rate of preterm birth in women receiving 17-OH progesterone?

birth in women receiving 17-OH progesterone? Kelly Ruhstaller, Matthew Hoffman, Anthony Sciscione, Nicole Doyle Christiana Care Health System, Obstetrics and Gynecology, Newark, DE OBJECTIVE: To evaluate whether maternal body mass index (BMI) impacts the rate of preterm birth in women receiving 17-OH progesterone caproate (17-OHPC) for a history of preterm delivery. STUDY DESIGN: All patients from the High Risk Clinic who delivered between March 2009 to July 2012 and received 17-OHPC were selected (n 144). Patients were excluded if they did not have a prior preterm birth, had a multifetal gestation, did not receive 17-OHPC prior to 20 weeks, had fetal anomalies or were delivered prior to 37 weeks for an indication other than preterm premature rupture of membranes (n 91). Women who also received a cerclage were included. The primary outcome was spontaneous delivery prior to 37 0/7 weeks. Secondary outcomes were delivery prior to 34 0/7 weeks, delivery prior to 28 0/7 weeks and composite neonatal morbidity (NICU admission, 5-minute APGAR 7 and birthweight 2500g). Women were divided into two groups, BMI 30 (kg/m) and 30 (kg/m). Odds ratios were calculated using BMI 30 as the referent group. RESULTS: In total 35 patients had a BMI 30 and 56 patients had BMI 30 (range 19.5-55.8). Women with a BMI 30 were significantly less likely to deliver prior to 37 0/7 weeks (OR 0.315, 95%CI 0.1280.722) and prior to 34 0/7 weeks (OR 0.282, 95%CI 0.102-0.778) when compared to women with a BMI 30. No significant difference in the rate of delivery prior to 28 0/7 weeks was seen (OR 1.046, 95%CI 0.234-4.68). There was a trend towards lower neonatal morbidity for infants born to women with a BMI 30, however this did not reach significance (OR 0.432, 95%CI 0.182-1.027). CONCLUSION: Obese women receiving 17-OHPC for a history of preterm birth have lower rates of repeat preterm delivery, except very early preterm births ( 28 weeks), compared to their normal weight and overweight counterparts. Additionally, the infants born to obese mothers have a lower overall neonatal morbidity. These findings may lead to further research into the mechanism behind the increased rate of preterm birth in lower weight women.
Performance of Observation-Based Prediction Algorithms for Very Short-Range, Probabilistic Clear-Sky Condition Forecasting

Abstract Very short-range sky condition forecasts are produced to support a variety of military, civil, and commercial activities. In this investigation, six advanced, observation (obs)-based prediction algorithms were developed and tested that generated probabilistic sky condition forecasts for 1-, 2-, 3-, 4-, and 5-h forecast intervals, for local and regional target types, in six geographic regions within the continental United States. Three of the methods were based on predictive learning algorithms including neural network, random forest, and regression tree. The other three methods were statistical techniques including a k–nearest neighbor algorithm, a classifier based on the Bayes decision rule, and a multialgorithm ensemble. The performances of these six algorithms were compared with forecasts from three benchmark methods: basic persistence, the climatological-expectancy-of-persistence, and satellite cloud climatology. The obs database for each forecast target was composed of a multiyear, half-hour...