cssi/SciSciGPT-SciSciNet huggingface dataset:
Mapping and mutagenesis of the amino-terminal transcriptional repression domain of the Drosophila Krüppel protein.

Abstract We previously demonstrated that the Drosophila Kruppel protein is a transcriptional repressor with separable DNA-binding and transcriptional repression activities. In this study, the minimal amino (N)-terminal repression region of the Kruppel protein was defined by transferring regions of the Kruppel protein to a heterologous DNA-binding protein, the lacI protein. Fusion of a predicted alpha-helical region from amino acids 62 to 92 in the N terminus of the Kruppel protein was sufficient to transfer repression activity. This putative alpha-helix has several hydrophobic surfaces, as well as a glutamine-rich surface. Mutants containing multiple amino acid substitutions of the glutamine residues demonstrated that this putative alpha-helical region is essential for repression activity of a Kruppel protein containing the entire N-terminal and DNA-binding regions. Furthermore, one point mutant with only a single glutamine on this surface altered to lysine abolished the ability of the Kruppel protein to repress, indicating the importance of the amino acid at residue 86 for repression. The N terminus also contained an adjacent activation region localized between amino acids 86 and 117. Finally, in accordance with predictions from primary amino acid sequence similarity, a repression region from the Drosophila even-skipped protein, which was six times more potent than that of the Kruppel protein in the mammalian cells, was characterized. This segment included a hydrophobic stretch of 11 consecutive alanine residues and a proline-rich region.
Impact of Androgen Deprivation Therapy on Mental and Emotional Well-Being in Men with Prostate Cancer: Analysis from the CaPSURE™ Registry

Purpose: While androgen deprivation therapy can delay cancer progression and reduce tumor burden, its use can be limited by adverse side effects. We evaluated the effect of androgen deprivation therapy on mental and emotional well-being in men with nonmetastatic prostate cancer.Materials and Methods: Participants were enrolled in the national CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry, and treated with radical prostatectomy, external beam radiation therapy or brachytherapy with no androgen deprivation therapy (local); local with androgen deprivation therapy (combination); or primary androgen deprivation therapy. Emotional quality of life was evaluated by SF-36® social function, role emotional, vitality and mental health subscales before and up to 24 months after treatment. Subscales were assessed as continuous scores and as clinically meaningful declines of at least half a standard deviation since pretreatment. Associations between treatment and quality of life changes ...
An efficient software-controlled PLL for low-frequency applications

The concept of a software-controlled phase-locked loop (SCPLL) is presented. It is shown that SCPLLs can offer several advantages over pure hardware implementations. An example design of an SCPLL for a power converter controller is presented, and the experimental results are reported. This SCPLL can efficiently substitute for the conventional hardware PLL used for timing and clock frequency multiplication in the control circuit of a power converter. >
Validating Animal Models

In this paper, I respond to the challenge raised against contemporary experimental neurobiology according to which the field is in a state of crisis because of the multiple experimental protocols employed in different laboratories and strengthening their reliability that presumably preclude the validity of neurobiological knowledge. I provide an alternative account of experimentation in neurobiology which makes sense of its experimental practices. I argue that maintaining a multiplicity of experimental protocols and strengthening their reliability are well justified and they foster rather than preclude the validity of neurobiological knowledge. Thus, their presence indicates thriving rather than crisis of experimental neurobiology.
Designing contact lenses for a wide field of view via ocular wavefront tomography

Purpose Correcting the off-axis wavefront aberration is potentially important for peripheral vision, for diagnostic imaging of the retina, and for influencing refractive development. A new technique called ocular wavefront tomography (OWT) was adapted to optimize the design of contact lenses to improve the eye's peripheral optical quality.
RISK FACTORS FOR AN OUTBREAK OF LEPTOSPIROSIS IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS) IN CALIFORNIA, 2004

Leptospirosis has been reported in California sea lions (Zalophus californianus) since 1970; however, the source of infection and mode of transmission remain unknown. To elucidate these features, demographic and environmental risk factors for leptospirosis were evaluated. California sea lion stranding records from northern California for 2004 were used to identify cases of leptospirosis (n = 316) and controls (n = 143). Demographic characteristics (age class, sex) and environmental factors, representing surrogates for exposure to dogs, cattle, rainfall, and freshwater sources, were compared between cases and controls with the use of a geographic information system (GIS) and logistic regression. Multivariate analyses revealed that summer and autumn seasons, juvenile age class, male sex, high dog-park density, and close proximity to dog parks were significantly associated with leptospirosis in sea lions, whereas county farmland cattle density, rainfall levels 30 days prior to stranding, human density, and proximity to freshwater sources were not associated. Thus, dogs and dog parks, or factors associated with them, might be further investigated to assess their relationship to leptospirosis in sea lions.
Development of a Model to Describe the Compositional Growth and Dietary Lysine Requirements of Pigs Fed Increasing Dietary Concentrations of Ractopamine

Abstract Two ractopamine (RAC) step-up programs were evaluated for their economic returns using a swine growth simulation program that incorporated growth responses to constant and to increased RAC concentrations. Dietary lysine concentrations were optimized to maximize daily returns above feed costs for 3 phases: (1) before RAC supplementation, (2) the first half of the RAC feeding period (14 or 18 d), and (3) the second half of the RAC feeding period. Diets were assumed to be corn-soybean meal based diets. Two durations of RAC feeding were evaluated, 28 and 35 d. The model compared constant RAC concentrations (0, 5, or 10 ppm) and two step-up programs in which 5 ppm RAC was fed the first half of RAC feeding period followed by either 7.5 or 10 ppm RAC. The initial BW of pigs at the start of the second phase diet was set at 78 and 72 kg for the 28- and 35-d feeding durations, respectively. Two payment schemes were used: one set the lean-to-fat price ratio at 4:1, close to true carcass cut-out value, and the other set the lean-to-fat price ratio to 2:1, approximating carcass merit pricing systems. The 5 to 10 ppm step-up had the greatest daily returns, followed by the 5 to 7.5 ppm step-up, the constant RAC feeding, and the control. Step-up programs were predicted to be more profitable than feeding constant dietary RAC concentrations.
The Clash of Aristocratic and Bourgeois Virtues in 'The Wire'

We use the classes of systematized ethics in Deirdre McCloskey's "The Bourgeois Virtues" to understand characters in HBO’s "The Wire" and the story of "The Wire" to understand the bourgeois ethics of the marketplace. McCloskey argues that the introduction of a new system of bourgeois ethics, distinct from the age-old ethical systems of the aristocrat, peasant, and priest classes, is responsible for the exponential growth in world GDP per capita since 1800. We explore the difference in ethical systems present in both "The Wire’s" West Baltimore drug economy in the 2000s and the world economy around 1800, aristocratic and bourgeois, and the challenge in transitioning from the broad poverty maintenance of the former system to the wealth-creating potential of the latter. The story of "The Wire" provides a rich case study in this clash.
Topographic Surgical Anatomy of the Parasylvian Anterior Temporal Artery for Intracranial-Intracranial Bypass.

Background The anterior temporal artery (ATA) is an appealing donor artery for intracranial-intracranial bypass procedures. However, its identification may be difficult. Current literature lacks useful landmarks to help identify the ATA at the surface of the sylvian fissure. The objective of this study was to define the topographic anatomy of the cortical segment of the ATA relative to constant landmarks exposed during the pterional approach. Methods The temporopolar artery (TPA), ATA, and middle temporal artery (MTA) were examined in 16 cadaveric specimens. The topographic anatomy and key landmarks of the arteries at the sylvian fissure were recorded. The distance between the point of emergence from the sylvian fissure to the lesser sphenoid wing and anterior tip of the temporal lobe was measured. The features of the inferior frontal gyrus relative to each of the arteries at the sylvian fissure were also recorded. Results The average distances from the lesser sphenoid wing to the TPA, ATA, and MTA were 3.7 mm, 21.2 mm, and 37 mm. The mean distances from the temporal pole were TPA, 14.7 mm; ATA, 32.0 mm; and MTA, 45.4 mm. The differences between the average distances were statistically significant ( P Conclusions This article provides topographic evidence for efficient identification of the ATA in the parasylvian space. The key relationship and landmarks identified in this study may increase efficiency and safety when harvesting the ATA for intracranial-intracranial bypass.
The NIST Uncertainty Machine

Abstract:The NIST Uncertainty Machine (http://uncertainty.nist.gov) is a web-based software application produced by the National Institute of Standards and Technology (NIST) to evaluate the measurement uncertainty associated with a scalar output quantity that is a known and explicit function of a set of input quantities for which estimates and evaluations of measurement uncertainty are available. Input and output quantities are modeled as random variables and their probability distributions are used to characterize measurement uncertainty. The NIST Uncertainty Machine implements the approximate method of uncertainty evaluation described in the “Guide to the expression of uncertainty in measurement” (GUM), and the Monte Carlo method of the GUM Supplement 1 (GUM-S1). The NIST Uncertainty Machine is freely accessible worldwide from any computer connected to the World Wide Web. Using a Web browser, the user specifies all the necessary information in an easy-to-use form. The calculations are performed on a NIS...
Advanced large signal modeling of vacuum electronic devices based on impedance characterization of slow-wave structures

Rapid but accurate 2D modeling of vacuum electronic devices today makes use of so-called hybrid codes1,2. These codes owe their computational efficiency to the fact that the properties of the slow-wave structures can be pre-calculated, and then fed to a beam wave interaction code, which calculates electron trajectories and self-fields in the beam-tunnel. While this approach has been successful (these codes are used throughout US industry) there are drawbacks that make optimization and sensitivity studies of existing designs and exploration of new designs difficult. The problem lies if the varied and sometimes imprecise information about a structure is input to the beam-wave interaction code. We propose a unifying framework for the calculation of structure properties and implementation of these properties in hybrid code based on generalized impedance and admittance matrices.
Engineered Liver Platforms for Different Phases of Drug Development

Drug-induced liver injury (DILI) remains a leading cause of drug withdrawal from human clinical trials or the marketplace. Owing to species-specific differences in liver pathways, predicting human-relevant DILI using in vitro human liver models is crucial. Microfabrication tools allow precise control over the cellular microenvironment towards stabilizing liver functions for weeks. These tools are used to engineer human liver models with different complexities and throughput using cell lines, primary cells, and stem cell-derived hepatocytes. Including multiple human liver cell types can mimic cell–cell interactions in specific types of DILI. Finally, organ-on-a-chip models demonstrate how drug metabolism in the liver affects multi-organ toxicities. In this review we survey engineered human liver platforms within the needs of different phases of drug development.
Perspective: Beyond the genome.

We need to combine epidemiology and exposures research to fulfil the potential of precision medicine, say John Leppert and Chirag Patel.
Decay of Yb 162

The decay of $^{162}\mathrm{Yb}$ was studied with samples produced by irradiating $^{164}\mathrm{Er}$ with 52-MeV $^{3}\mathrm{He}$ ions. Mass separation of the irradiated samples provided isotopically pure $^{162}\mathrm{Yb}$ samples for half-life and $\ensuremath{\gamma}$-ray spectra measurements. Three $\ensuremath{\gamma}$ rays (44-, 118-, and 162-keV in energy) as well as the Tm $K$ x rays were observed and the half-life of $^{162}\mathrm{Yb}$ was determined to be 18.87 \ifmmode\pm\else\textpm\fi{} 0.19 min. The latter two $\ensuremath{\gamma}$ rays were found only in coincidence with Tm $K$ x rays but not with each other. From the growth and decay of the 102-keV $\ensuremath{\gamma}$ ray of $^{162}\mathrm{Tm}$ in these same samples, the abundances of the three $\ensuremath{\gamma}$ rays and the Tm $K{\ensuremath{\alpha}}_{1}$ x ray were determined.
Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes.

Author(s): Pulvers, Kim; Emami, Ashley S; Nollen, Nicole L; Romero, Devan R; Strong, David R; Benowitz, Neal L; Ahluwalia, Jasjit S | Abstract: BackgroundThere is considerable debate about the benefits and risks of electronic cigarettes (ECs). To better understand the risk-benefit ratio of ECs, more information is needed about net nicotine consumption and toxicant exposure of cigarette smokers switching to ECs.MethodsForty cigarette smokers (≥1 year of smoking) interested in switching to ECs but not necessarily quitting smoking were enrolled in a 4-week observational study and provided an e-Go C non-variable battery and refillable atomizers and choice of eight flavors in 12 or 24 mg nicotine dosage. Measurement of urinary cotinine (metabolite of nicotine), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a pulmonary carcinogen), and eight volatile organic compounds (VOCs) that are toxic tobacco smoke constituents was conducted at baseline and week 4.ResultsAll participants with follow-up data (92.5%) reported using the study EC. Of the 40 smokers, 16 reported no cigarettes at week 2 (40%) and six continued to report no cigarettes at week 4 (15%). Change in nicotine intake over the 4 weeks was non-significant (p = .90). Carbon monoxide (p l .001), NNAL (p l .01) and metabolites of benzene (p l .01) and acrylonitrile (p = .001) were significantly decreased in the study sample. Smokers switching exclusively to ECs for at least half of the study period demonstrated significant reductions in metabolites of ethylene oxide (p = .03) and acrylamide (p l .01).ConclusionSmokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.ImplicationsThis study extends current literature by measuring change in smoking dependence and disease-associated biomarkers, NNAL and a panel of eight common VOCs that are toxic tobacco smoke constituents in smokers who switch to ECs. The findings support the idea of harm reduction, however some levels of toxicant exposure are still of clinical concern, particularly for dual users. Extrapolation of these results must be careful to separate the different toxic exposure results for exclusive switchers versus dual cigarette + EC users, and not to equate harm reduction with the idea that using ECs is harmless.
Future Directions for Research on Online Technical Education

ABSTRACTMost research on online learning in higher education has been focused on general education at four-year institutions. There is a need for more research that focuses on online and hybrid education at community colleges in technical education fields. This issue includes articles from eight National Science Foundation funded projects doing innovative work on the use of online and hybrid learning in technical education. Examination of these articles suggests several potential directions for future research in this area including the following: how to choose between fully online and hybrid course delivery; how technical education programs can successfully partner with industry; how to examine and select specific online educational strategies to enhance online technical education; how to sustain innovative online educational programs after grant funding is complete; and how to support nontraditional students in online or hybrid technical education programs.
Fibrous Latex-Modified Concrete Overlay For Bridge Decks: Installation and Life-Cycle Cost analysis

This paper presents a case study of pioneering installation of fibrous latex-modified concrete (LMC) overlay in Chicago, Illinois as a major task of a three-year research project completed in 2012. The objective of the project was to investigate the potential performance benefits that can be obtained when incorporating synthetic fibers into the mix designs of bridge deck concrete overlays without jeopardizing the constructability. Prior to the field demonstration, an extensive laboratory program was conducted to evaluate the major performance characteristics of various overlay mixtures with and without fibrous additives in terms of workability and finishability, compressive and flexural strengths, shrinkage, toughness, permeability, and bond strength. For further evaluation of the constructability of the fibrous LMC overlay taking into consideration actual field conditions, a demonstration bridge was selected and received fibrous LMC overlay through actual Illinois Department of Transportation (IDOT) contract. The paper presents the followed steps toward successful installation of the fibrous LMC overlay. In addition, life-cycle cost analyses were conducted to compare the costs of the LMC to micro-silica concrete (MSC) overlays using actual costs of IDOT overlay projects.
A new equi-dimensional fracture model using polyhedral cells for microseismic data sets

Abstract We present a method for modeling flow in porous media in the presence of complex fracture networks. The approach utilizes the Mimetic Finite Difference (MFD) method. We employ a novel equi-dimensional approach for meshing fractures. By using polyhedral cells we avoid the common challenge in equi-dimensional fracture modeling of creating small cells at the intersection point. We also demonstrate how polyhedra can mesh complex fractures without introducing a large number of cells. We use polyhedra and the MFD method a second time for embedding fracture boundaries in the matrix domain using a “cut-cell” paradigm. The embedding approach has the advantage of being simple and localizes irregular cells to the area around the fractures. It also circumvents the need for conventional mesh generation, which can be challenging when applied to complex fracture geometries. We present numerical results confirming the validity of our approach for complex fracture networks and for different flow models. In our first example, we compare our method to the popular dual-porosity technique. Our second example compares our method with directly meshed fractures (single-porosity) for two-phase flow. The third example demonstrates two-phase flow for the case of intersecting ellipsoid fractures in three-dimensions, which are typical in microseismic analysis of fractures. Finally, we demonstrate our method on a two-dimensional fracture network produced from microseismic field data.
Interoperability at the tactical edge: Lessons learned from Enterprise Challenge 2016

In August, 2016, the Army Research Laboratory (ARL) participated in Enterprise Challenge 2016 at Ft. Huachuca. Incorporating an Expeditionary Processing, Exploitation and Dissemination (Ex-PED) model, ARL demonstrated the utility of tactical wide-area and persistent sensing in a bandwidth constrained environment, the effectiveness of a Sensor 3-D Common Operating Picture (COP) to enable appropriate sensor management, and the ability to seamlessly incorporate coalition sensors into the ARL exercise enterprise as well as the broader event enterprise.
Deep-learning: investigating deep neural networks hyper-parameters and comparison of performance to shallow methods for modeling bioactivity data

In recent years, research in artificial neural networks has resurged, now under the deep-learning umbrella, and grown extremely popular. Recently reported success of DL techniques in crowd-sourced QSAR and predictive toxicology competitions has showcased these methods as powerful tools in drug-discovery and toxicology research. The aim of this work was dual, first large number of hyper-parameter configurations were explored to investigate how they affect the performance of DNNs and could act as starting points when tuning DNNs and second their performance was compared to popular methods widely employed in the field of cheminformatics namely Naive Bayes, k-nearest neighbor, random forest and support vector machines. Moreover, robustness of machine learning methods to different levels of artificially introduced noise was assessed. The open-source Caffe deep-learning framework and modern NVidia GPU units were utilized to carry out this study, allowing large number of DNN configurations to be explored. We show that feed-forward deep neural networks are capable of achieving strong classification performance and outperform shallow methods across diverse activity classes when optimized. Hyper-parameters that were found to play critical role are the activation function, dropout regularization, number hidden layers and number of neurons. When compared to the rest methods, tuned DNNs were found to statistically outperform, with p value <0.01 based on Wilcoxon statistical test. DNN achieved on average MCC units of 0.149 higher than NB, 0.092 than kNN, 0.052 than SVM with linear kernel, 0.021 than RF and finally 0.009 higher than SVM with radial basis function kernel. When exploring robustness to noise, non-linear methods were found to perform well when dealing with low levels of noise, lower than or equal to 20%, however when dealing with higher levels of noise, higher than 30%, the Naive Bayes method was found to perform well and even outperform at the highest level of noise 50% more sophisticated methods across several datasets.
Three-Year Analysis of Value and Utilization After Development of an Ultrasound-Based Orthopedic Injection Clinic.

ABSTRACT Introduction: Sonography is an effective method of diagnosing and treating musculoskeletal conditions, and the use of ultrasound has been shown to improve the accuracy, safety, and efficacy of both therapeutic and diagnostic injections. In 2012, we established an injection clinic at our institution to address our growing need for diagnostic and therapeutic injections. Methods: We performed an analysis of value and utilization following the development of an orthopedic injection clinic. This included an evaluation of the cost of materials, equipment, and training required to develop and run the clinic, and an analysis of the services rendered and relative value units (RVUs) generated over 3 fiscal years (FYs). Results: The cost to develop the clinic was $42,498.30. The cost to run the clinic thereafter was $16.90 to $21.60 per injection. By the end of FY 2012, 60% of providers performed at least 1 injection under ultrasound guidance. Every successive year thereafter, 100% of providers were using u...
American Magnitude: Frederic Church, Hiram Bingham, and Hemispheric Vision

Starting in the mid-nineteenth century, travelers from the United States regularly shared pictures of their South American adventures with US audiences increasingly eager to imagine US influence sp...
Advanced Process Simulation - Laser and Flash Annealing

Summary form only given. Continuing a trend that began with RTA, anneals continue to shrink in time and increase in temperature. The latest developments are with either flash lamp anneals in the millisecond regime or laser anneals which can be as short as nanoseconds. From a modeling perspective, there are three key challenges in accomplishing of accurately modeling these anneal cycles. First, whenever the substrate is used as a heat sink, the spatial variation of temperature is important. Most process simulators do not allow for this. This paper have addressed this and it has been fixed in FLOOPS over the last two years. This paper discuss techniques employed to minimize computational overhead in doing this. Second, the simulator must solve the heat flow equation to help generate the spatial and temporal variation of temperature. FLOOPS' scripting language is well suited to this task, and built preliminary models that help predict the onset of melting, for example. Finally, these models need to be calibrated. Can equilibrium models of heat transport be used at this time and length scale? How critical is carrier transport to the heat removal? Preliminary experimental and simulation results are presented from this regime that indicate where the pressing problems exist.
Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus

Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces.
Kinetics of Methylmercury Production Revisited.

Laboratory measurements of the biologically mediated methylation of mercury (Hg) to the neurotoxin monomethylmercury (MMHg) often exhibit kinetics that are inconsistent with first-order kinetic models. Using time-resolved measurements of filter passing Hg and MMHg during methylation/demethylation assays, a multisite kinetic sorption model, and reanalyses of previous assays, we show that competing kinetic sorption reactions can lead to time-varying availability and apparent non-first-order kinetics in Hg methylation and MMHg demethylation. The new model employing a multisite kinetic sorption model for Hg and MMHg can describe the range of behaviors for time-resolved methylation/demethylation data reported in the literature including those that exhibit non-first-order kinetics. Additionally, we show that neglecting competing sorption processes can confound analyses of methylation/demethylation assays, resulting in rate constant estimates that are systematically biased low. Simulations of MMHg production and...
Smads In Drosophila – Interpretation Of Graded Signals In Vivo

Drosophila has both BMP and Activin signaling pathways, but little is known about the functions of the Activin/TGF-β class of signals in this organism. BMP signaling has been intensively studied in this organism, and Drosophila continues to stand as a paradigm for understanding the functions of BMPs in development. Drosophila BMPs can induce different cell fates at different concentrations, a critical property for extracellular signals that direct spatial patterning of tissues. Although the endogenous BMP ligands are difficult to detect, spatial patterns of cells with phosphorylated R-Smad and nuclear co-Smad reveal the graded distribution of BMP activity in the embryonic ectoderm and the wing primordium. The question of how cells interpret different levels of BMP activity has been a major focus for studies of Smads in Drosophila. We review the general modes for Smad regulation of BMP target genes, including direct repression of gene expression, indirect induction through release from repression, and direct activation of gene expression. These studies integrate the mechanisms for gene regulation by Smads with the logic of spatial and temporal regulation of development by BMPs
Regulation of Thrombin Receptor Signaling

Thrombin, a coagulant protease, is generated at sites of vascular injury and elicits cellular responses critical for haemostasis and thrombosis, as well as inflammation and proliferation. Protease-activated receptors (PARs) are G-protein-coupled receptors that account for the majority of thrombin’s effects on cells. PAR1, the prototype for this family, is the predominant mediator of thrombin signaling in most cell types. PAR3 and PAR4 also respond to thrombin and are differentially expressed in various cell types. PARs are uniquely activated by proteolysis, which results in the generation of a tethered ligand that cannot diffuse away, unlike normal reversibly activated G-protein-coupled receptors. Since PARs are irreversibly activated, signaling must be tightly regulated. Desensitization and trafficking of proteolytically activated PARs control the magnitude, duration and spatial aspects of receptor signaling. Thrombin also elicits cell-type-specific response through the activation of distinct PARs and G-protein subtypes. Thus, elucidating the mechanisms that regulate PAR signaling in various cell types is critical for understanding their biological function. Here, I discuss our current understanding of the regulation of thrombin receptor signaling.
Financial education and insurance advice seeking

The purpose of this study is to examine the potential effects of consumer financial education on insurance advice seeking with a large and representative national data set in the U.S. Previous research has examined factors associated with insurance advice seeking. After controlling for these factors, financial education, which has not been examined in previous research, is positively associated with this behaviour. Specifically, high school and workplace financial education show positive associations with insurance advice seeking. Further analyses show that there are differences in insurance advice seeking between consumers with and without life insurance.
Comparison of Methods for Analyzing Global Positioning System and Accelerometer Data during School Recess

Several geospatial approaches have been used to characterize physical activity during recess using global positioning system (GPS) data. GPS and accelerometer data from 23 children collected during...
Acceleration of rare disease therapeutic development: a case study of AGIL-AADC.

Rare-disease drug development is both scientifically and commercially challenging. This case study highlights Agilis Biotherapeutics (Agilis), a small private biotechnology company that has developed the most clinically advanced adeno-associated virus (AAV) gene therapy for the brain. In an international collaboration led by Agilis with National Taiwan University (NTU) Hospital and the Therapeutics for Rare and Neglected Diseases (TRND) program of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health, Agilis’ gene therapy for aromatic l -amino acid decarboxylase deficiency (AADC), AGIL-AADC, was granted biologics license application (BLA)-ready status by the FDA in 2018, only 18 months after being licensed from NTU by Agilis. Here, we highlight the factors that enabled this remarkable pace of successful drug development for an ultra-rare disease.
Spatially continuous strain monitoring using distributed fiber optic sensors embedded in carbon fiber composites

A distributed fiber optic strain sensor based on Rayleigh backscattering, embedded in a fiber-reinforced polymer composite, has been demonstrated. The optical frequency domain reflectometry technique is used to analyze the backscattered signal. The shift in the Rayleigh backscattered spectrum is observed to be linearly related to the change in strain of the composite material. The sensor (standard single-mode fiber) is embedded between the layers of the composite laminate. A series of tensile loads is applied to the laminate using an Instron testing machine, and the corresponding strain distribution of the laminate is measured. The results show a linear response indicating a seamless integration of the optical fiber in the composite material and a good correlation with the electrical-resistance strain gauge results. The sensor is also used to evaluate the strain response of a composite-laminate-based cantilever beam. Distributed strain measurements in a composite laminate are successfully obtained using an embedded fiber optic sensor.
Prediction of elemental glass-transition temperatures of metals from thermophysical properties of liquids

Abstract Since extremely high quench rates (1012 to 1014 K/s) are normally necessary to form elemental metallic glasses, very few are known. Even when synthesized, very little is known about their properties because of the limited quantities of material produced under such extreme conditions. In particular, the glass transition temperature, Tg, of most of the elemental glasses are unknown. Here, predictions of Tg for many elemental metals are made based on the properties of the liquids. The basis for these predictions comes from a number of recently observed correlations in metallic alloy liquids between the liquid fragility, thermal expansion coefficient, rate of change of liquid structure with temperature, and cohesive energy. Using those quantitative correlations and the properties of elemental liquids, T g ′ s for several metallic elements are predicted. Where experimental data are available, they are in reasonable agreement with these predictions.
SELF-DECEPTIVE RESISTANCE TO SELF-KNOWLEDGE

Philosophical accounts of self-deception have tended to focus on what is necessary for one to be in a state of self-deception or how one might arrive at such a state. Less attention has been paid to explaining why, so often, self-deceived individuals resist the proper explanation of their condition. This resistance may not be necessary for self-deception, but it is common enough to be a proper explanandum of any adequate account of the phenomenon. The goals of this essay are to analyze this resistance, to argue for its importance to theories of self-deception, and to offer a view of self-deception that adequately accounts for it. The view’s key idea is that, in at least some familiar cases, self-deceived individuals maintain their condition by confusing a nonepistemic satisfaction they take in their self-deceived beliefs for the epistemic satisfaction that is characteristic of warranted beliefs. Appealing to this confusion can explain both why these self-deceived individuals maintain their unwarranted belief and why they resist the proper explanation of their condition. If successful, the essay will illuminate the nature of belief by examining the limits of the believable.
Amyloid Beta-Related Alterations to Glutamate Signaling Dynamics During Alzheimer's Disease Progression.

Alzheimer’s disease (AD) ranks sixth on the Centers for Disease Control and Prevention Top 10 Leading Causes of Death list for 2016, and the Alzheimer’s Association attributes 60% to 80% of dementi...
Role of rapid diagnostics for viral respiratory infections in antibiotic prescribing decision in the emergency department

OBJECTIVE To describe the frequency of antibiotic prescriptions in patients with known viral respiratory infections (VRIs) diagnosed by polymerase chain reaction (PCR) in 3 emergency departments (EDs) and to identify patient characteristics that influence the prescribing of antibiotics by ED physicians despite PCR confirmation of viral cause. DESIGN Retrospective, observational analysis of patients with PCR-diagnosed VRI discharged from 3 acute-care hospital EDs within 1 health system. RESULTS In total, 323 patients were discharged from the ED with a VRI diagnosis, of whom 68 were prescribed antibiotics (21.1%). These patients were older (median, 59.5 vs 43 years; P = .04), experienced symptoms longer (median, 4 vs 2 days; P = .002), were more likely to have received antibiotics in the preceding 7 days (27.9% vs 9.8%; P < .001), and had higher proportions of abnormal chest X-rays (64.5% vs 28.4%; P < .001). Patients were more likely to receive antibiotics for a diagnosis of pneumonia (39.7% vs 1.6%; P < .001) or otitis media (7.4% vs 0.4%; P = .002), and were less likely with diagnosis of upper respiratory infection (2.9% vs 13.7%; P = .02) or influenza (20.6% vs 44.3%; P < .001). CONCLUSIONS Despite a diagnosis of VRI, one-fifth of ED patients were prescribed antibiotics. Patient characteristics including age, duration of symptoms, abnormal chest X-rays, and specific diagnosis may increase provider concern for concurrent bacterial infections. Opportunities exist for antimicrobial stewardship strategies to incorporate rapid diagnostics in promoting judicious antibiotic usage in the ED.
Novel High-Throughput Quantitation of Potent hERG Blocker Dofetilide in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Application in a Phase 1 ECG Biomarker Validation Study.

The authors developed a novel, sensitive high-throughput ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of dofetilide in human plasma. To compensate for the matrix effect, a deuterated internal standard was used. The method employed a very low sample volume (50 μL) of plasma for sample processing by using simple protein precipitation extraction in a 96-well plate. The extracted samples were chromatographed on an Acquity BEH C18 column (2.1 × 100 mm, 1.7 μm) and eluted in a gradient manner at a flow rate of 0.5 mL/min for 2 min using 5 mM ammonium formate (0.1% formic acid) and methanol. The calibration curve was linear from 25 to 2,500 pg/mL with a correlation coefficient (r2) ≥ 0.99 (0.9969-0.9980; n = 3). The developed method was validated as per the current United States Food and Drug Administration's guidance for industry on 'Bioanalytical Method Validation'. The multiple reaction-monitoring mode was employed for quantitation of dofetilide with m/z 442.2/198.2 and dofetilide d4 with m/z 446.2/198.2. The validated method was used for evaluation of dofetilide concentration in the Comprehensive in vitro Proarrhythmia Assay phase 1 electrocardiogramic biomarker validation study.
Spherical nanoindentation on tungsten single crystal: The transition from source-controlled plasticity to bulk plasticity

Abstract Spherical nanoindentation was performed on tungsten single crystal to investigate the effects of tip radius on the pop-in stress. The results show that the pop-in stress decreases as the tip radius increases. A statistical model with randomly distributed dislocation sources captures experimentally observed source-controlled indentation size effect. The discrepancy between model and experimental data especially for a large tip was corrected by considering the collective activation of multiple dislocation sources. Our results provide a quantitative insight into the understanding of the transition from source-controlled plasticity to bulk plasticity under spherical nanoindentation.
Fetal growth standards for Somali population.

Accurate assessment of fetal size is essential in providing optimal prenatal care. National Institute of Child Health and Human Development (NICHD) study from 2015 demonstrated that estimated fetal...
Diagonal Controller Tuning

Distillation columns are inherently multi-variable. As discussed in Chapter 1, even the most simple single-feed, two-product column is a 5 × 5 system: five manipulated variables and five controlled variables. The column can normally be reduced to a 2 × 2 system because the control loops for the two liquid levels and the pressure do not interact significantly in many columns. Thus we have in the simplest of distillation columns a system with two compositions or two temperatures that can be controlled and two manipulated variables to achieve this control.
Factors Associated With the Choice of Radiation Therapy Treatment Facility in Head and Neck Cancer

OBJECTIVE To analyze the clinicodemographic characteristics and treatment outcomes of patients receiving postoperative radiation therapy (PORT) at a different treatment facility rather than the initial surgical facility for head and neck cancer. STUDY DESIGN Retrospective cohort analysis. METHODS Utilizing the National Cancer Data Base, 2004 to 2015, patients with a diagnosis of oral cavity/oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinoma were studied. Multivariate analysis was completed with multivariate regression and Cox proportional hazard model, and survival outcomes were examined using Kaplan-Meier analysis. RESULTS A total of 15,181 patients who had surgery for a head and neck cancer at an academic/research center were included in the study population. Of the study population, 4,890 (32.2%) patients completed PORT at a different treatment facility. Treatment at a different facility was more common among patients who were ≥65 years old, white, Medicare recipients, those with a greater distance between residence and surgical treatment facility, and with lower income within area of residence (each P < .05). Overall survival was worse in patients completing PORT at a different treatment facility versus at the institution where surgery was completed (61.9% vs. 66.4%; P = .002). CONCLUSIONS PORT at a different facility was more common in older individuals, Medicare recipients, those with greater distance to travel, and lower-income individuals. Completing PORT outside the hospital where surgery was performed was associated with inferior survival outcomes among head and neck cancer patients. LEVEL OF EVIDENCE 3 Laryngoscope, 131:1019-1025, 2021.
Cervical Vascular Injuries: Techniques

The complex anatomical relationships within a small area make the diagnosis and management of both penetrating neck vascular injuries (PNVI) and blunt neck vascular injuries (BNVI) challenging. Radiographic evaluation continues to evolve, with a shift from invasive to noninvasive diagnostics. The epidemiology of penetrating and blunt vascular injuries to the neck is distinctly different. Among penetrating injuries, firearms are responsible for about 43%, stab wounds for about 40%, shotguns for about 4%, and other weapons for about 12%. Overall, about 35% of all gunshot wounds (GSWs) and 20% of stab wounds (SWs) to the neck cause significant injuries, but only 16% of GSWs and 10% SWs require surgical therapy. Even though transcervical GSWs cause significant injuries in 73% of victims, only 21% require surgery. Although BNVI is common, when cervical spine injuries are excluded, injuries to the remaining structures are rare. Though uncommon, blunt cerebrovascular injuries can be lethal. With increased appreciation and availability of noninvasive diagnostics, the rates of these injuries are now between 1.0% and 2.0%.
The essay film after fact and fiction: edited by Nora M. Alter, New York: Columbia University Press, 2018, Film and Culture series. 416 pp., $32.00 (Paperback), ISBN 978-0-2311-7821-1; $105.00 (Hardcover), ISBN 978-0-2311-7820-4; $31.99 (E-book), ISBN 978-0-2315-4598-3

Nora Alter begins her thorough exploration of the essay film, an elusive genre of nonfiction filmmaking, by noting that when she began its exploration two decades ago few people knew what she was t...
From within the shadows of the everyday: Localized entrepreneurship and the dilemma of scale

Economic re-localization is widely viewed as a principal mechanism for bringing greater autonomy, democracy, justice, prosperity, and general wellness to communities. Entrepreneurial initiatives th...
Teaching Early Learners With Autism to Follow Written Directions: Making Text Mediate Action to Promote Independence:

Many individuals with autism spectrum disorder (ASD) can effectively decode and read words fluently, but have significantly below-average understanding of text. Following written directions may hol...
TIGER: Topological Interlocking GEneratoR

Topological Interlocking is a design technique to generate non-monolithic structures and composite materials. A traditional topological interlocking assembly consists of convex blocks arranged in a single layer. A peripheral structure provides support for the blocks and prevents lateral strain. Recent research on this topic has found remarkable properties that are not present with more traditional design techniques or material approaches. Despite the advances and increasing interest, there is no available software that contains all the essential tools to generate and analyze such structures. We introduce TIGER, a software application to generate and analyze topological interlocking configurations based on 3D surface tessellations. The application provides generation methods for both tessellations and interlocking assemblies. The analysis of the assemblies is based on the Structure Feasibility method that finds the minimum tension magnitudes for the structure to maintain a static equilibrium state. The generated configurations can be saved in multiple file formats for later 3D printing and additional analysis using more sophisticated tools.
Heat Transfer to Helium-II in Cylindrical Geometries

Renewed interest in the properties of helium-II has been inspired by numerous new engineering applications for the fluid [1–3]. Of particular concern is the heat transfer behavior and its effect on the design of stable superconducting magnets. Studies of heat transfer to helium-II in linear systems have investigated such phenomena as peak heat transport, including superfluidity breakdown [4–7], effects of normal fluid turbulence [8–9], and time-dependent heat transfer [10–11]. In general, experiments with cylindrical geometries have been limited to measurements of the peak heat flux from a cylindrical heater or wire in an open bath. On the basis of experience with the linear system, it appears clear that to characterize cylindrical heat transfer, a careful accounting of the heat flow in the adjacent helium is necessary.