cssi/SciSciGPT-SciSciNet huggingface dataset:
Sturgeon's Defence of Moral Realism

Can a moral principle be tested and confirmed empirically? Can the fact that an event exhibits a moral quality play a role in explaining why a person observes the event as having that quality? Gilbert Harman, in attempting to point to a radical difference between scientific and moral facts, has endorsed a negative answer to these questions. With Harman's discussion in mind, Nicholas Sturgeon takes the affirmative side in his “Moral Explanations,” a potentially influential essay that is now beginning to appear in the textbook anthologies. Sturgeon rounds out his defence of moral realism by further arguing that moral qualities of persons can play an essential role in the scientific explanation of human conduct. Finally, he attempts to enhance the appeal of moral realism by arguing for the plausibility of its compatibility with physicalism. While granting that Sturgeon's discussion is challenging and instructive I shall try to show that on all points mentioned here Sturgeon has failed to make a good case.
Droplet Array Platform for High-Resolution Melt Analysis of DNA Methylation Density

High-resolution melting (HRM) has garnered significant interest as an analytical technique for a number of applications, including DNA methylation detection, due to its inherent sensitivity and robustness. In this study, we describe a miniaturized assay platform for quantitative methylation density analysis using a microfluidic droplet array cartridge. We demonstrate that the DNA methylation level of the RASSF1A promoter can be directly analyzed using HRM. PCR products were generated by amplifying bisulfite-treated DNA with varying CpG densities using CpG island-flanking primer sets. Subsequent HRM analysis on the miniaturized droplet platform shows distinct melting curve profiles associated with methylation levels, which was verified using a conventional benchtop PCR-HRM system. The characteristic melting temperature (Tm) of the PCR products was used to directly quantify the respective levels of DNA methylation density. Our approach provides a key advantage over current gold standard methods such as methylation-specific PCR (MSP), which are incapable of providing specific information regarding the overall methylation density of the target genes. The miniaturized platform establishes a practical approach to methylation density profiling from multiple DNA samples with a potential application in point-of-care diagnostics.
College Recruiting a Portfolio of Expectations

Each year America's industries and colleges join forces in an action aimed at converting the engineering student into an engineer employee. Principals in this operation are the company recruiter and the college placement director. Through the years each member of this unique alliance has come to learn the strength and weaknesses of his partner; each has profited and suffered through the other; each has developed his own ideas on how the other should operate. IRE TRANSACTIONS ON EDUCATION recently asked a number of executives on company recruiting staffs and college placement offices for their opinions on the current state of college recruiting, and for suggestions on improving the operation in future years. This two-part article presents excerpts from some of the replies received.
Radiosensitization of Cancer Cells by Inactivation of Cullin-RING E3 Ubiquitin Ligases

Although radiotherapy represents one of the most effective treatment modalities for patients with cancer, inherent and/or acquired resistance of cancer cells to radiotherapy is often an impediment to effective treatment. Diverse strategies have been developed to improve the efficacy of radiotherapy. The ubiquitin-proteasome system (UPS) operates in numerous vital biologic processes by controlling the protein turnover in cells. Ubiquitination is central to the UPS pathway, and it relies on the E3 ubiquitin ligases to catalyze the covalent attachment of ubiquitin to its protein substrates. Cullin-based RING ligases (CRLs) are the largest family of E3 ligases that are responsible for the ubiquitination and destruction of numerous cancer-relevant proteins. Its deregulation has been linked to many human cancers, making it an attractive target for therapeutic intervention. This review discusses how targeting the ubiquitin-proteasome system, particularly CRLs, is an exciting new strategy for radiosensitization in cancer and, specifically, focuses on MLN4924, a recently discovered small-molecule inhibitor of the NEDD8-activating enzyme, which is being characterized as a novel radiosensitizing agent against cancer cells by inactivating CRL E3 ubiquitin ligases.
Narrative and Legitimacy: U.S. Congressional Debates about the Nonprofit Sector

This article develops a theory about the narrative foundations of public policy. Politicians draw on specific types of narratives in order to connect the policies they are proposing, the needs of the public, and their own needs for legitimacy. In particular, politicians are drawn to policy narratives in which they themselves occupy the central and heroic character position, and where they are able to protect the scope of their jurisdictional authority. We demonstrate how this works through a historical analysis of congressional debate about the nonprofit sector in the United States. Two competing narratives framed these debates: (1) a selfless charity narrative, in which politicians try to empower heroic charity workers and philanthropists, and then stay out of the way; and (2) a masquerade narrative, in which fake charities are taking advantage of the nonprofit tax exemption, in order to pursue a variety of noncivic and dangerous activities. Members of Congress quickly adopted the masquerade narrative as...
FliW and FliS Function Independently To Control Cytoplasmic Flagellin Levels in Bacillus subtilis

The cytoplasmic level of flagellin (called Hag) is homeostatically regulated in the Gram-positive bacterium Bacillus subtilis by a partner-switching mechanism between the protein FliW and either the Hag structural protein or CsrA, an RNA binding protein that represses hag translation. Here we show that FliW and the putative secretion chaperone FliS bind to Hag simultaneously but control Hag translation by different mechanisms. While FliW directly inhibits CsrA activity, FliS antagonizes CsrA indirectly by binding to Hag, enhancing Hag secretion, and depleting Hag in the cytoplasm to trigger the FliW partner switch. Consistent with a role for FliS in potentiating Hag secretion, the mutation of fliS crippled both motility and flagellar filament assembly, and both phenotypes could be partially rescued by artificially increasing the concentration of the Hag substrate through the absence of CsrA. Furthermore, the absence of FliS resulted in an approximately 30-fold reduction in extracellular Hag accumulation in cells mutated for CsrA (to relieve homeostatic control) and the filament cap protein FliD (to secrete flagellin into the supernatant). Thus, we mechanistically discriminate between the FliW regulator and the FliS chaperone to show that secretion disrupts flagellin homeostasis and promotes high-level flagellin synthesis during the period of filament assembly in B. subtilis.
Experimental Autoimmune Encephalomyelitis Induction in Genetically B Cell–deficient Mice

Experimental autoimmune encephalomyelitis (EAE) is an animal model for autoimmune central nervous system disease mediated by CD4 T cells. To examine the role of B cells in the induction of EAE, we used B10.PL (I-Au) mice rendered deficient in B cells by deletion of their μ chain transmembrane region (B10.PLμMT). By immunizing B10.PL and B10.PLμMT mice with the NH-terminal myelin basic protein encephalitogenic peptide Ac1-11, we observed no difference in the onset or severity of disease in the absence of mature B cells. There was, however, a greater variation in disease onset, severity, and especially of recovery in the B cell–deficient mice compared to controls. B10.PLμMT mice rarely returned to normal in the absence of B cells. Taken together, our data suggest that B cells do not play a role in the activation of encephalitogenic T cells, but may contribute to the immune modulation of acute EAE. The mechanisms to explain these effects are discussed.
Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates

In this study, we tested the hypothesis that hypertrophic cell volume varies directly with the rate of longitudinal bone growth. The volume of hypertrophic chondrocytes (using stereological techniques) and longitudinal bone growth per 24 h (using oxytetracycline labeling techniques) were measured in the proximal and distal radial growth plates and the proximal and distal tibial growth plates of 21- and 35-day-old hooded rats and 21- and 35-day-old Yucatan pigs. We demonstrated a high coefficient of correlation (rats 0.98, pigs 0.83) between the final volume of hypertrophic chondrocytes and the rate of longitudinal bone growth over a wide range of growth rates and volumes of hypertrophic chondrocytes. In addition, we demonstrated a positive linear relationship between the rate of longitudinal bone growth and the final volume of hypertrophic chondrocytes. The slope of the regression line was different for rats than for pigs. The relationship was independent of the location of the growth plate in the animal and the age of the animal. The data suggest that mechanisms regulating volume changes in hypertrophic chondrocytes may exist and that chondrocytic volume increase is a major determinant of the rate of longitudinal bone growth. However, the relative contribution of cellular hypertrophy to longitudinal bone growth may be different in rats than in pigs.
Emulsion polymerization with water soluble comonomers in batch and continuous reactors

Emulsion copolymerization reactions which include monomers that have significant solubility in the water phase are described and modeled. The reactions that take place in the aqueous phase are considered as is the influence of water-soluble comonomers on radical transport out of the monomer-swollen polymer particles. Experimental characterization of the oligomers formed in the aqueous phase is also a subject of this paper.
Lotus Effect coating and its application for microelectromechanical systems stiction prevention

The stiction problem is one of the major factors that limit the widespread use and reliability of microelectromechanical systems (MEMS). The fundamental mechanism to prevent stiction is either increasing the surface roughness, or coating MEMS surfaces with hydrophobic materials. By nature, the Lotus Effect coating is a good combination of rough surface and hydrophobic materials. In this work, the feasibility of using Lotus Effect coatings to prevent MEMS stiction was proposed and investigated. Lotus Effect surfaces were either prepared by creating nanoscale rough structures on a hydrophobic surface with plasma techniques, or by coating functional self-assembled monolayers (SAMs) on nanoporous silica substrates. The effects of surface chemistry and structure on the superhydrophobicity of Lotus Effect materials were studied. The relationship between surface structure, surface wetting, and surface stiction properties of a Lotus Effect surface was also investigated.
Anxiolytic medication is an independent risk factor for 30-day morbidity or mortality after surgery

Background This study examined the effects of the use of anxiolytic medications (AXM) and antidepressant medications (ADMs) on outcomes after noncardiac surgery. Study design A single-center review of prospectively obtained, perioperative and 30-day outcome data, including AXM and ADM use at admission, as part of the National Surgery Quality Improvement Program. Results Of the 1846 patients undergoing surgery, 380 (20.6%) were taking an ADM, 288 (15.6%) AXM, 124 (6.7%) were taking both, and 545 (29.5%) were taking either at the time of admission. Both ADM and AXM patients more often were female than nonusers, had a greater American Society of Anesthesiologists class and suffered more from hypertension, COPD, and dyspnea (all P P P = .023). Conclusion AXM was used by 16% of patients in our institution undergoing a noncardiac operation and was an independent risk factor for poorer short-term outcome after surgery. ADM was found to be used by 21% of patients but was not an independent risk factor for poor outcome.
Genetic studies of natural populations of Drosophila: Drosophila pseudoobscura, a large dominant population.

FOR several years members of this laboratory have studied the genetic structure of Drosophila populations. None of these populations has been a large dominant continental population. PROFESSOR TH. DOBZHANSKY and his colleagues have analyzed samplemf Drosophila willistoni, the major Neotropical Drosophila with the largest population of any Drosophila known, and Drosophila pseudoobscura, which is the dominant population in numbers and distribution in the western United States and extends through Mexico and Guatemala. The studies with D. pseudoobscura are summarized and extended by DOBZHANSKY, SPASSKY and TIDWELL (1963 and references therein). PROFESSOR DOBZHANSKY spent the summer of 1961 in Arizona collecting and analyzing populations of D. pseudoobscura. He provided this laboratory with large samples of two of the populations he was testing and DR. WILLIAM B. HEED collected two other populations of D. pseudoobscura so that there were four samples from as many localities to compare. These parallel investigations on samples of the same population have the added advantage that one can compare directly the results of the two methods of analysis. MATERIALS AND METHODS
Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay.

Cytotoxic effector T cells of F1 (BALB/c X BALB.B) (H-2d/b) mice immunized against the minor histocompatibility differences of C57BL/10 (H-2b) can lyse targets from C57BL/10, but cannot lyse B10.D2 (H-2d) targets. Despite this lack of cross-reaction in the cytotoxic assay, C57BL/10 cells do prime F1 (BALB/c X BALB.B) mice for a secondary cytotoxic response to B10.D2. C57BL/10-primed, B10.D2-boosted cytotoxic cells lyse B10.D2 targets but not C57BL/10 targets. DBA/2 (H-2d) spleen cells or thymocytes prime F1 mice for a secondary response to DBA/2, B10.D2, and C57BL/10 cells, but DBA/2 mastocytes, P815, do not prime for a response to C57BL/10. Whether H-2 congenic lymphoid cells express minor histocompatibility determinants which cross-react at the cytotoxic T-cell level or the helper T-cell level is discussed.
Effects of cardiovascular surgery on blood concentrations of taurine and amino acids.

AbstractConcentrations of taurine and other amino acids were measured in whole blood and plasma of patients who were subjected to either cardiac surgery which involved known cardiac trauma or noncardiac vascular surgery in which cardiac trauma was not expected. In all surgical procedures within 24 hr taurine levels in whole blood increased by 50 to 80% above control values. The concentration of taurine in plasma did not increase postsurgery thus indicating that a cellular component(s) of the blood was sequestering taurine. Fluctuations were also noted in the blood levels of some of the other amino acids but the changes were either not as pronounced as were the taurine elevations or were decreases in concentration. The results indicate that fluctuations in blood taurine levels do not constitute reliable indices to quantitate myocardial injury in the postoperative patient.
Optimizing Gold Nanoparticle Cluster Configurations (n ≤ 7) for Array Applications.

Nanoparticle cluster arrays (NCAs) are novel electromagnetic materials whose properties depend on the size and shape of the constituent nanoparticle clusters. A rational design of NCAs with defined optical properties requires a thorough understanding of the geometry-dependent optical response of the building blocks. Herein, we systematically investigate the near- and far-field responses of clusters of closely packed 60 nm gold nanoparticles (n ≤ 7) as a function of size and cluster geometry through a combination of experimental spectroscopy and generalized Mie theory calculations. From all of the investigated cluster configurations, nanoparticle trimers with D3h geometry and heptamers in D6h geometry stand out due to their polarization-insensitive responses and high electric (E) field intensity enhancements, making them building blocks of choice in this size range. The near-field intensity maximum of the D6h heptamer is red-shifted with regard to the D3h trimer by 125 nm, which confirms the possibility of...
Primate antisaccades. I. Behavioral characteristics.

Amador, Nelly, Madeleine Schlag-Rey, and John Schlag. Primate antisaccades. I. Behavioral characteristics. J. Neurophysiol. 80: 1775–1786, 1998. The antisaccade task requires a subject to make a sa...
Basic Fractional Integral Inequalities

Here we present basic fractional integral inequalities for left and right Riemann-Liouville, generalized Riemann-Liouville, Hadamard, Erdelyi-Kober and multivariate Riemann-Liouville fractional integrals.
A Silicogermanate with a Si:Ge Ratio ≥ 2. - A Novel MFI-Zeolite.

Substitution of Ge for Si in pure SiO2-zeolites yields microporous materials containing Si and Ge in a tetrahedral framework of the MFI-type.
An idealized self or the real me? Predicting attraction to online dating profiles using selective self-presentation and warranting

ABSTRACTOnline daters construct their profiles to attract potential partners and viewers’ assessments are based on the content of dating profiles. However, little is known about the mechanisms or nature of the associations that connect variations in profile content to outcomes. This study examined the presence of selective self-presentation (SSP) and warranting content as predictors of viewers’ impressions and intentions to act on dating profiles. A national sample of online daters (N = 316) provided their impressions and intended outcomes after viewing manipulated dating profiles. Results indicate that high levels of SSP decrease intentions to act on a dating profile because users find these profiles to be less socially attractive, whereas profiles with high warranting value increase positive outcomes by eliciting trust.
Ancillary Fiberoptic Equipment

Summary To be successful at fiberoptic intubation, the anesthetist must have a clean, functioning fiberoptic laryngoscope and a well-organized assortment of ancillary equipment readily at hand. A portable cart containing the items outlined in this chapter is a way of assuring the availability of all necessary items at a moment's notice, ready for use in the remotest corners of the hospital.
Modeling Variability in the Progression of Huntington's Disease A Novel Modeling Approach Applied to Structural Imaging Markers from TRACK-HD

We present a novel, general class of disease progression models for Huntington's disease (HD), a neurodegenerative disease caused by a cytosine-adenine-guanine (CAG) triplet repeat expansion on the huntingtin gene. Models are fit to a selection of structural imaging markers from the TRACK 36-month database. The models are of mixed effects type and should be useful in predicting any continuous marker of HD state as a function of age and CAG length (the genetic factor that drives HD pathology). The effects of age and CAG length are modeled using flexible regression splines. Variability not accounted for by age, CAG length, or covariates is modeled using terms that represent measurement error, population variability (random slopes/intercepts), and variability due to the dynamics of the disease process (random walk terms). A Kalman filter is used to estimate variances of the random walk terms.
Measuring Sheet Resistances of Dielectrics Using Co‐Planar Hydrogel Electrochemical Cells with Practical Applications to Characterize the Protective Quality of Paints on Sculptures

Electrical properties of thin dielectric films at the solid-liquid phase boundary are an important performance characteristic of many devices, coatings and sensors. In this paper, co-polymeric hydrogels of polyacrylic acid co-sulfonic acid, swollen with a salt solution to act as the solid electrolyte, were used to assess interfaces using electrochemical impedance spectroscopy (EIS) in a co-planar geometry. Silane-modified glasses were characterized by the co-planar hydrogel EIS cell and found to be distinguishable based on their surface monolayer chemistry. EIS measurements were also made on primed and painted metal substrates, using both test panels and an outdoor sculpture, Tony Smith's Stinger. The panels were then exposed to accelerated and outdoor weathering and showed degradation on the surface paint layers, which was observable electrochemically using EIS and confirmed visually by SEM. Electrochemical spectral features were compared between data from a standard paint-test cell versus this co-planar hydrogel cell; both cell types were able to measure coating capacitance, providing useful information about the condition of the bulk coating. Yet, sheet resistance (Rs) was a spectral feature seen only by the co-planar hydrogel cell. Thus, it can be concluded that the use of such co-planar hydrogel cells can provide an earlier warning sign to coating degradation and such cells provide a new type of spectral information that is not assessable by the standard geometry.
Connective Tissue Diseases and the Heart

Many of the multisystem inflammato Interry connective tissue disorders promote or are linked to increased risk of atherosclerosis and its sequelae. Systemic lupus erythematosus patients often have verrucous endocarditis or valvular thickening with regurgitation or stenosis. Patients with antiphospholipid antibodies may develop spontaneous venous or arterial thromboses.
What We Know About Stage II and III Colon Cancer: It’s Still Not Enough

The introduction of oxaliplatin as adjuvant treatment for stage III colon cancer in 2004 has been the last practice changing progress in adjuvant treatment for patients with early colon cancer. Since then, many prognostic and predictive biomarkers have been studied, but only DNA mismatch repair status has been validated as having an important prognostic value. Accordingly, TNM and clinical-pathological patterns, such as pT4 lesions and lymph node sampling <12 nodes, are the main factors that guide physicians' choice regarding adjuvant treatment. More recently, many biomarkers showed promising results: POLE, ErbB2, CDX2, SMAD4, BRAF and KRAS. In addition to these, immune-contexture, molecular classification, and gene signatures could become new ways to better classify colon cancer patients with more discriminatory power than TNM. The aim of this review is to report the state-of-the-art of prognostic and predictive factors in the adjuvant setting and which of these could modify clinical practice and maybe replace TNM classification.
From the Editor's Desk: TOCE Continues on a Positive Trajectory in 2016

During my first full year as editor-in-chief of ACM Transations on Computing Education (TOCE), the editorial board and I took the following four steps to improve the journal's ability to serve the growing community of computing education researchers: (1) We streamlined the peer review process, (2) we established a new partnership with the ACM Special Interest Group on Computer Science Education Conference, (c) we transitioned to a double-blind review process, and (4) we recruited guest editors for two new special issues that address timely research topics. In this editorial, I present key statistics on TOCE's review process and submissions during the 2016 calendar year, discuss and reflect on the positive steps we took to improve the journal during 2016, and describe steps we will consider in the coming year in order to ensure that ACM TOCE continues on its positive trajectory. These include forging additional partnerships with professional conferences, altering the review criteria to make the journal more welcoming to a broader range of research, especially within the K-12 space, and developing a set of evidence standards for research published in the journal.
A Systems Perspective on Practicum Experiences in Early Childhood Teacher Education: Focus on Interprofessional Relationships.

High quality early childhood teachers have a wealth of knowledge and use a range of skills in their daily classroom practices, and research has consistently demonstrated the positive influence effective early childhood teachers have on children’s development and long-term outcomes. Given the importance of practicum experiences in the development of effective teachers, exploration and understanding of these experiences for early childhood teacher candidates is warranted. The relationship between the cooperating teacher and teacher candidate can be viewed as a central element in the experience; this relationship influences and is influenced by additional elements within the practicum experience, including: communication, beliefs, fit, knowledge and learning. In this article, each of these elements is explored, and the interrelatedness of the elements within the practicum experience is discussed. A systems perspective is used to describe the multiple elements of the practicum experiences in early childhood teacher preparation programs, not only to explore the practicum experience, but also to develop recommendations and a research agenda.
Inclusion of Body Bias Effect in SPICE Modeling of 4H-SiC Integrated Circuit Resistors

The DC electrical behavior of n-type 4H-SiC resistors used for realizing 500 C durable integrated circuits (ICs) is studied as a function of substrate bias and temperature. Improved fidelity electrical simulation is described using SPICE NMOS model to simulate resistor substrate body bias effect that is absent from the SPICE semiconductor resistor model.
Applications of Structured Light Microscopy in Clinical Pathology

Structured light microscopy, including structured illumination microscopy (SIM) and selective plane illumination microscopy (SPIM), has a number of compelling applications in clinical pathology, including large-area rapid 2D imaging for core biopsy and tumor margin assessment, rapid nondestructive 3D cytology, and comprehensive 3D analysis of tumor architecture with isotropic resolution. This talk will briefly introduce our work in these areas, focusing on the use of SIM for tumor margin imaging.
Behavior Decomposition: Aspect-Level Browser Extension Clustering and Its Security Implications

Browser extensions are widely used by millions of users. However, large amount of extensions can be downloaded from webstores without sufficient trust or safety scrutiny, which keeps users from differentiating benign extensions from malicious ones. In this paper, we propose an aspect-level behavior clustering approach to enhancing the safety management of extensions. We decompose an extension's runtime behavior into several pieces, denoted as AEBs Aspects of Extension Behavior. Similar AEBs of different extensions are grouped into an "AEB cluster" based on subgraph isomorphism. We then build profiles of AEB clusters for both extensions and categories of extensions to detect suspicious extensions. To the best of our knowledge, this is the first study to do aspect-level extension clustering based on runtime behaviors. We evaluate our approach with more than 1,000 extensions and demonstrate that it can effectively and efficiently detect suspicious extensions.
Geology, Soils, and Sediments

Within a given climatic regime, soil properties are the major factor governing ecosystem processes. This chapter provides background on the factors regulating those soil and sediment properties that most strongly influence ecosystems as well as the transport of materials from land to rivers, lakes, and the ocean.
Steepest Descent as a Tool to Find Critical Points of ∫ k2 Defined on Curves in the Plane with Arbitrary Types of Boundary Conditions

We will explicitly compute the gradient of the total squared curvature functional on a space of parametrized curves of fixed or variable length satisfying arbitrary types of boundary conditions. We show how to turn the space of such curves into an infinite dimensional submanifold of an inner product space. The steepest descent will then be along the integral curves of the negative gradient vector field in this manifold. We will derive the gradients and the corresponding flow equations. In conclusion we use computer graphics to illustrate this process by following one such trajectory starting close to an unstable critical point and ending at a stable critical point.
Ken Thompson: Playing Chess

The famous “ken” of UNIX and C and UTF, whom Ken Regan knew beginning in 1971 from the Westfield Chess Club in New Jersey, pioneered computer chess through his program Belle and the compilation of tables giving perfect play in certain endgames. This chapter surveys data structures and algorithms for these tables.
Easy and hard testbeds for real-time search algorithms

Although researchers have studied which factors influence the behavior of traditional search algorithms, currently not much is known about how domain properties influence the performance of real-time search algorithms. In this paper we demonstrate, both theoretically and experimentally, that Eulerian state spaces (a superset of undirected state spaces) are very easy for some existing real-time search algorithms to solve: even real-time search algorithms that can be intractable, in general, are efficient for Eulerian state spaces. Because traditional real-time search testbeds (such as the eight puzzle and gridworlds) are Eulerian, they cannot be used to distinguish between efficient and inefficient real-time search algorithms. It follows that one has to use non-Eulerian domains to demonstrate the general superiority of a given algorithm. To this end, we present two classes of hard-to-search state spaces and demonstrate the performance of various real-time search algorithms on them.
Informative ecological models without ecological forces

Sagoff (Synthese 193:3003–3024, 2016) criticizes widely used “theoretical” methods in ecology; arguing that those methods employ models that rely on problematic metaphysical assumptions and are therefore uninformative and useless for practical decision-making. In this paper, I show that Sagoff misconstrues how such model-based methods work in practice, that the main threads of his argument are problematic, and that his substantive conclusions are consequently unfounded. Along the way, I illuminate several ways the model-based inferential methods he criticizes can be, and have been, usefully informative.
Solitary waves in bistable lattices with stiffness grading: Augmenting propagation control

In this study we introduce small perturbations in the forms of graded intersite stiffnesses and graded on-site potentials to a lattice composed of bistable unit cells under elastic interactions. Based on a known soliton solution in the $\ensuremath{\phi}$-4 model, we use a perturbation approach to approximate the effects of the perturbations on the propagation speeds of transition waves. Numerical validations follow on the exact discrete equations of motion, from which we observe eventual stoppage of transition waves in the periodic lattice under physical damping, unidirectional propagation of the waves in the direction of softening properties, and boomerang-like reflection of the waves in the stiffening direction. Finally, we present three-dimensional-printed experimental lattices, confirming the theoretical and numerical results. The observed behaviors imply the extreme controllability of solitary waves through slight engineering manipulations in material-level structures. We further find that both kink (rarefaction) and antikink (compression) waves are allowed at any site in the lattice, extending the functionality of the lattice in engineering applications such as energy harvesting.
A step forward for an attenuated blood-stage malaria vaccine.

Efforts to develop an effective malaria vaccine have encountered multiple challenges, and have had limited success to date. As the need remains urgent, novel approaches must be explored. One concept that has gained attention uses whole malaria parasites. Building on preclinical studies in animal models, Stanisic et al. describe the development of a vaccine based on chemically attenuated Plasmodium falciparum blood-stage parasites, with an evaluation of safety and immunogenicity in malaria-naive human subjects. The vaccine was shown to be safe, well tolerated, and capable of priming antigen-specific T cells. This work, and the completion of an initial clinical trial in human subjects, represents a significant advance. While the path forward for this attenuated vaccine remains challenging, these initial findings are encouraging. Importantly, the results provide the foundation and framework for testing modified immunization protocols, and designing subsequent clinical trials to further evaluate safety, test for enhanced immunogenicity, and ultimately measure protective efficacy.Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1173-9.
Real-Time Time-Resolved Optical Measurements using a Digital Adaptive Filter

We demonstrate a novel phosphorescence lifetime imaging microscopy technique using a pseudo-random modulated laser source for excitation, and an adaptive filter for resolving the detected emission. Our results show clear lifetime differences between the oxygenated and deoxygenated solutions of a ruthenium dye.
Data-Driven Detection of Sustained Oscillations and Frequency Mode in Power Systems

Sustained oscillations in power systems can damage equipment, raise the risks of blackouts, and impact power quality in general. This work presents a novel method to detect low-frequency oscillations and identify frequency modes by applying measured data from high resolution sensors like Phasor Measurement Units (PMU). An algorithm based on reduced dimensionality of the data for detection of oscillations is proposed. A Slow Feature Analysis (SFA) is applied to extract low-dimensional features from the measured data. Based on the Recurrence Quantification Analysis (RQA), two thresholds are applied to identify low-frequency oscillations by using the slow features. The recurrence-derived Fourier Transform (FT) is applied to determine frequency modes. Studies on a 29-machine 179-bus system show the effectiveness of the proposed method.
Stochastic estimation approach for the evaluation of thermal-hydraulic parameters in pressurized water reactors

A method based on the extended Kalman filter is developed for the estimation of the core coolant mass flow rate in pressurized water reactors. The need for flow calibration can be avoided by a direct estimation of this parameter. A reduced-order neutronic and thermal-hydraulic model is developed for the Loss-of-Fluid Test (LOFT) reactor. The neutron detector and core-exit coolant temperature signals from the LOFT reactor are used as measurements in the parameter estimation algorithm. The estimation sensitivity to model uncertainties was evaluated using the ambiguity function analysis. This also provides a lower bound on the measurement sample size necessary to achieve a certain estimation accuracy. A sequential technique was developed to minimize the computational effort needed to discretize the continuous time equations, and thus achieve faster convergence to the true parameter value. The performance of the stochastic approximation method was first evaluated using simulated random data, and then applied to the estimation of coolant flow rate using the operational data from the LOFT reactor at 100 and 65% flow rate conditions.
Establishing a theoretical foundation for measuring global health security: a scoping review

Since the 2014–2016 West Africa Ebola epidemic, the concept of measuring health security capacity has become increasingly important within the broader context of health systems-strengthening, enhancing responses to public health emergencies, and reducing global catastrophic biological risks. Efforts to regularly and sustainably track the evolution of health security capabilities and capacities over time – while also accounting for political, social, and environmental risks – could help countries progress toward eliminating sources of health insecurity. We sought to aggregate evidence-based principles that capture a country’s baseline public health and healthcare capabilities, its health security system performance before and during infectious disease crises, and its broader social, political, security, and ecological risk environments. We conducted a scoping review of English-language scholarly and gray literature to identify evidence- and practice-based indicators and proxies for measuring health security at the country level over time. We then used a qualitative coding framework to identify recurrent themes in the literature and synthesize foundational principles for measuring global health security. Documents reviewed included English-language literature published after 2001 until the end of the research period—September 2017—to ensure relevance to the current global health security landscape; literature examining acute infectious disease threats with potential for transnational spread; and literature addressing global health security efforts at the country level. We synthesized four foundational principles for measuring global health security: measurement requires assessment of existing capacities, as well as efforts to build core public health, healthcare, and biosecurity capabilities; assessments of national programs and efforts to mitigate a critical subset of priority threats could inform efforts to generate useful metrics for global health security; there are measurable enabling factors facilitating health security-strengthening efforts; and finally, measurement requires consideration of social, political, and ecological risk environments. The themes identified in this review could inform efforts to systematically assess the impacts and effectiveness of activities undertaken to strengthen global health security.
Probing Membrane Dynamics Using Simultaneous Second Harmonic Generation and Two-Photon Excitation Fluorescence Spectroscopy

Small molecule-membrane interactions were studied in bacteria using second harmonic generation and two-photon fluorescence spectroscopy. Results suggest membrane kinetics are highly dependent on molecular size and membrane compositions.
AAV Capsid-Promoter Interactions Determine CNS Cell-Selective Gene Expression In Vivo.

Cell-selective gene expression comprises a critical element of many adeno-associated virus (AAV) vector-based gene therapies, and to date achieving this goal has focused on AAV capsid engineering, cell-specific promoters, or cell-specific enhancers. Recently, we discovered that the capsid of AAV9 exerts a differential influence on constitutive promoters of sufficient magnitude to alter cell type gene expression in the rat CNS. For AAV9 vectors chicken β-actin (CBA) promoter-driven gene expression exhibited a dominant neuronal gene expression in the rat striatum. Surprisingly, for otherwise identical AAV9 vectors, the truncated CBA hybrid (CBh) promoter shifted gene expression toward striatal oligodendrocytes. In contrast, AAV2 vector gene expression was restricted to striatal neurons, regardless of the constitutive promoter used. Furthermore, a six-glutamate residue insertion immediately after the VP2 start residue shifted CBA-driven cellular gene expression from neurons to oligodendrocytes. Conversely, a six-alanine insertion in the same AAV9 capsid region reversed the CBh-mediated oligodendrocyte expression back to neurons without changing AAV9 capsid access to oligodendrocytes. Given the preponderance of AAV9 in ongoing clinical trials and AAV capsid engineering, this AAV9 capsid-promoter interaction reveals a previously unknown novel contribution to cell-selective AAV-mediated gene expression in the CNS.
Microglia-Müller cell interactions in the retina.

Microglia and Muller cells are cell types that feature prominently in responses to disease and injury in the retina. However, their mutual interactions have not been investigated in detail. Here, we review evidence that indicate that these two cell populations exchange functionally significant signals under uninjured conditions and during retinal inflammation. Under normal conditions, Muller cells constitute a potential source of extracellular ATP that mediates the activity-dependent regulation of microglial dynamic process motility. Following microglial activation in inflammation, microglia can signal to Muller cells, influencing their morphological, molecular, and functional responses. Microglia-Muller cell interactions appear to be a mode of bi-directional communications that help shape the overall injury response in the retina.
Assessment of Second-Generation Diabetes Medication Initiation Among Medicare Enrollees From 2007 to 2015

Importance Little is known about how new and expensive drugs diffuse into practice affects health care costs. Objective To describe the variation in second-generation diabetes drug use among Medicare enrollees between 2007 and 2015. Design, Setting, and Participants This population-based, cross-sectional study included data from 100% of Medicare Parts A, B, and D enrollees who first received diabetes drug therapy from January 1, 2007, to December 31, 2015. Patients with type 1 diabetes were excluded. Data were analyzed beginning in the spring of 2018, and revisions were completed in 2019. Exposures For each patient, the initial diabetes drug choice was determined; drugs were classified as first generation (ie, approved before 2000) or second generation (ie, approved after 2000, including dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide-1 [GLP-1] receptor agonists, and sodium-glucose cotransporter-2 [SGLT-2] inhibitors). Main Outcomes and Measures The primary outcome was the between-practice variation in use of second-generation diabetes drugs between 2007 and 2015. Practices with use rates of second-generation diabetes drugs more than 1 SD above the mean were considered high prescribing, while those with use rates more than 1 SD below the mean were considered low prescribing. Results Among 1 182 233 patients who initiated diabetes drug therapy at 42 977 practices between 2007 and 2015, 1 104 718 (93.4%) were prescribed a first-generation drug (mean [SD] age, 75.4 [6.7] years; 627 134 [56.8%] women) and 77 515 (6.6%) were prescribed a second-generation drug (mean [SD] age, 76.5 [7.2] years; 44 697 [57.7%] women). By December 2015, 22 457 practices (52.2%) had used DPP-4 inhibitors once, compared with 3593 practices (8.4%) that had used a GLP-1 receptor agonist once. Furthermore, 17 452 practices (40.6%) were using DPP-4 inhibitors in 10% of eligible patients, while 1286 practices (3.0%) were using GLP-1 receptor agonists in 10% of eligible patients, and SGLT-2 inhibitors, available after March 2013, were used at least once by 1716 practices (4.0%) and used in 10% of eligible patients by 872 practices (2.0%) by December 2015. According to Poisson random-effect regression models, beneficiaries in high-prescribing practices were more than 3-fold more likely to receive DPP-4 inhibitors (relative risk, 3.55 [95% CI, 3.42-3.68]), 24-fold more likely to receive GLP-1 receptor agonists (relative risk, 24.06 [95% CI, 14.14-40.94]) and 60-fold more likely to receive SGLT-2 inhibitors (relative risk, 60.41 [95% CI, 15.99-228.22]) compared with beneficiaries in low-prescribing practices. Conclusions and Relevance These findings suggest that there was substantial between-practice variation in the use of second-generation diabetes drugs between 2007 and 2015, with a concentration of use among a few prescribers and practices responsible for much of the early diffusion.
Self-guided field trips allow flexibility in undergraduate student introductory field experiences

There is a clear desire in the geoscience community to engage students in field work in ways that minimize institutional (cost, size, liability) and circumstantial barriers (family obligations, fin...
Digging Deeper: Considering the Marginalizing Experience of Homelessness in Developing Program Performance Objectives

Engaging citizens in performance work can be difficult and resource-intensive and may yield few instrumental benefits. Some argue it is still beneficial for democratic purposes as it enables govern...
Photometric Redshift Biases from Galaxy Evolution

Proposed cosmological surveys will make use of photometric redshifts of galaxies that are significantly fainter than any complete spectroscopic redshift surveys that exist to train the photo-z methods. We investigate the photo-z biases that result from known differences between the faint and bright populations: a rise in active galactic nucleus (AGN) activity toward higher redshift, and a metallicity difference between intrinsically luminous and faint early-type galaxies. We find that even very small mismatches between the mean photometric target and the training set can induce photo-z biases large enough to corrupt derived cosmological parameters significantly. Our results suggest that a metallicity shift of ~0.003 dex in an old population, or contamination of any galaxy spectrum with ~0.2% AGN flux, is sufficient to induce a 10-3 bias in photo-z. These results highlight the danger in extrapolating the behavior of bright galaxies to a fainter population, and the desirability of a spectroscopic training set that spans all of the characteristics of the photo-z targets, i.e., extending to the 25th mag or fainter galaxies that will be used in future surveys.
Trial in progress: A phase 1b/2 study of the PARP inhibitor niraparib in combination with trastuzumab in patients with metastatic HER2+ breast cancer (TBCRC 050).

TPS1098Background: Approximately 20% of breast cancers (BC) express the human epidermal growth factor receptor 2 (HER2). Although HER2-directed therapies result in improved patient outcome, resista...
Smart Health Integrated Framework and Topology (SHIFT) for Smart and Connected Community

A smart and connected communities (S&CC) will utilize existing and emerging technologies to collect heterogeneous spatiotemporally distributed data and artificial intelligence (AI) to seamlessly generate meaningful knowledge that will benefit both individuals and S&CC. We have developed a framework for Health and Wellbeing of S&CC that includes existing and emerging sensors for data collection from users of the community, a custom smartphone app with real-time AI algorithms for edge-computing, and a webserver for spatiotemporal visualization of abstracted information for community stakeholders. We propose to extend this framework towards an enhanced Smart Health Integrated Framework and Topology (SHIFT) through incorporating a uniform hierarchical layer-based architecture for S&CC. The proposed concept was simulated to depict data processing and visualization approach. The proposed framework takes advantage of evolving topology of smart sensors and devices, in addition to being transferable and scalable.
A Computational Learning Semantics for Inductive Empirical Knowledge

This chapter presents a new semantics for inductive empirical knowledge. The epistemic agent is represented concretely as a learner who processes new inputs through time and who forms new beliefs from those inputs by means of a concrete, computable learning program. The agent’s belief state is represented hyper-intensionally as a set of time-indexed sentences. Knowledge is interpreted as avoidance of error in the limit and as having converged to true belief from the present time onward. Familiar topics are re-examined within the semantics, such as inductive skepticism, the logic of discovery, Duhem’s problem, the articulation of theories by auxiliary hypotheses, the role of serendipity in scientific knowledge, Fitch’s paradox, deductive closure of knowability, whether one can know inductively that one knows inductively, whether one can know inductively that one does not know inductively, and whether expert instruction can spread common inductive knowledge—as opposed to mere, true belief—through a community of gullible pupils.