cssi/SciSciGPT-SciSciNet huggingface dataset:
Gas hydrate characterization and grain-scale imaging of recovered cores from the Mount Elbert Gas Hydrate Stratigraphic Test Well, Alaska North Slope

Abstract Using cryogenic scanning electron microscopy (CSEM), powder X-ray diffraction, and gas chromatography methods, we investigated the physical states, grain characteristics, gas composition, and methane isotopic composition of two gas-hydrate-bearing sections of core recovered from the BPXA–DOE–USGS Mount Elbert Gas Hydrate Stratigraphic Test Well situated on the Alaska North Slope. The well was continuously cored from 606.5 m to 760.1 m depth, and sections investigated here were retrieved from 619.9 m and 661.0 m depth. X-ray analysis and imaging of the sediment phase in both sections shows it consists of a predominantly fine-grained and well-sorted quartz sand with lesser amounts of feldspar, muscovite, and minor clays. Cryogenic SEM shows the gas-hydrate phase forming primarily as a pore-filling material between the sediment grains at approximately 70–75% saturation, and more sporadically as thin veins typically several tens of microns in diameter. Pore throat diameters vary, but commonly range 20–120 microns. Gas chromatography analyses of the hydrate-forming gas show that it is comprised of mainly methane (>99.9%), indicating that the gas hydrate is structure I. Here we report on the distribution and articulation of the gas-hydrate phase within the cores, the grain morphology of the hydrate, the composition of the sediment host, and the composition of the hydrate-forming gas.
Continuous Emission of Hydrogen Plasmas

The continuous absorption coefficients for the bound-free and free-free transitions of H and H− as well as the total absorption coefficients are given for hydrogen plasmas of 1, 10, 30, 100, and 300 atmos pressure and temperatures of 10 080, 12 600, and 16 800°K in the wavelength range from 2000 to 40 000 A. In order to calculate the free-free transitions of H− the tables of Chandrasekhar and Breen have been extended to include θ=0.4 and θ=0.3. The results of these calculations, namely the free-free absorption coefficients for H− per neutral hydrogen atom in the ground state and unit electron pressure, are given for θ=0.4 and θ=0.3. Finally, from the total absorption coefficients, the continuous emission from a 1-cm thick layer of the hydrogen plasmas under consideration has been derived. It is shown that for certain temperatures and pressures the continuous emission becomes so strong that the blackbody intensity of the corresponding temperature is reached for all wavelengths under consideration. This makes the plasma, in particular, useful for photolysis work and absorption spectroscopy.
On bootstrapping M-estimated residual processes in multiple linear regression models

Abstract It is shown, under fairly general conditions, that Efron′s bootstrap procedure captures the limit distribution of weighted empirical processes based on M -estimated residuals in multiple linear regression models. As an application, we construct bootstrap confidence bands for the error distribution function F . The main result can also be used to design distribution-free goodness-of-fit tests for F without any recourse to the split-sample estimation of the regression parameters.
Sluggish cognitive tempo in psychiatrically hospitalized children: factor structure and relations to internalizing symptoms, social problems, and observed behavioral dysregulation.

As research examining sluggish cognitive tempo (SCT) advances, it is important to examine the structure and validity of SCT in a variety of samples, including samples of children who are clinically-distressed but not referred specifically for attention-deficit/hyperactivity disorder (ADHD). The present study used a large sample of psychiatrically hospitalized children (N = 680; 73 % male; 66 % African American) between the ages of 6 and 12 to examine the latent structure of SCT, ADHD, oppositional defiant disorder (ODD), depression, and anxiety using confirmatory factor analysis (CFA). Results of the CFA analyses demonstrated that SCT is distinct from these other dimensions of child psychopathology, including ADHD inattention, depression, and anxiety. Regression analyses indicated that SCT symptoms were positively associated with depression and, to a lesser degree, anxiety. SCT symptoms were also positively associated with children’s general social problems, whereas SCT symptoms were negatively associated with an observational measure of behavioral dysregulation (i.e., frequency of time-outs received as a part of a manualized behavior modification program). These associations were significant above and beyond relevant child demographic variables (i.e., age, sex, race), children’s other mental health symptoms (i.e., ADHD, ODD, depression, anxiety symptoms), and, for all relations except child anxiety, parents’ own anxiety and depression symptoms.
Solution structure of the TAZ2 (CH3) domain of the transcriptional adaptor protein CBP.

The TAZ2 (CH3) domain of the transcriptional adapter protein CBP has been implicated in direct functional interactions with numerous cellular transcription factors and viral oncoproteins. The solution structure of the TAZ2 domain of murine CBP has been determined by nuclear magnetic resonance (NMR). The protein adopts a novel helical fold stabilized by three zinc ions, each of which is bound to one histidine and three cysteine ligands in HCCC-type motifs. Each zinc-binding site is formed from the carboxy terminus of an alpha-helix, a short loop, and the amino terminus of the next alpha-helix. A peptide derived from the N-terminal transactivation domain of p53 binds specifically to one face of the TAZ2 domain. The close similarities between the TAZ2 and TAZ1 (CH1 domain of CBP/p300) sequences suggest that both domains will adopt similar three-dimensional structures.
Systematic epidemiologic theory: Conceptual foundations and axiomatic elements

Since the initial epidemiologic confrontations of chronic, non-infectious diseases during the 1940's, there has emerged a periodic concern among epidemiologists regarding disciplinary boundaries and identity. With the development of hierarchical views of the natural history of human disease, the elaboration of mutation theories of chronic, non-infectious disease, and the identification of conceptual frameworks and causal relationships applicable to both the infectious and chronic, non-infectious diseases, it has become possible to reconsider the definitions and scope of epidemiology from within the confines of general epidemiologic-pathologic theory. Based upon natural history and discipline-related concepts of causation, it is possible to integrate the epidemiological and pathological characteristics of disease into a single, coherent systematic epidemiologic theory. Within these conceptual/axiomatic frameworks, systematic epidemiology emerges as the study of disease causality and control and is generally applicable to both the infectious and the chronic, non-infectious (i.e., neoplastic) diseases. Because epidemiologic theory begins with pathologic theory, it is fitting that systematic epidemiologic theory embrace both epidemiology and pathology as complimentary conceptual approaches to the comprehension of disease. Because the interdependent efforts of epidemiology and pathology provide the conceptual basis for action, it is also fitting that systematic epidemiologic theory embrace preventive medicine and public health as operational approaches to the control of disease.
Synthesis of a Chiral Bicyclo[4.1.0] Allylic Nitrile Via Reductive Cyclization of a Dienyl Nitrile

Abstract (1R, 6S)-7,7-dimethylbicyclo[4.1.0]Hept-2-ene-3-acetonitrile 8 was synthesized from (S)-(-)-Perillaldehyde in 5 steps and 65% overall yield via Mg[0] reductive cyclization.
One-step methods for ordinary differential equations

It is proved that any consistent one-step method for solving the initial value problem for a first-order ordinary differential equation is convergent; no stability condition is required. An application is made to a similarly stated result, allowing part of the hypothesis in that case to be dropped.
PRODUCT MARKET STRUCTURE, CAPITAL INTENSITY, AND SYSTEMATIC RISK: EMPIRICAL RESULTS FROM THE THEORY OF THE FIRM

Product market concepts from industrial organization economics are integrated with financial valuation models of the firm to investigate relationships among systematic risk, capital intensity, and product market power. The theory of the firm facing uncertain input and output prices is extended to provide empirical models. Empirical results coincide with hypotheses derived from the theoretical model and pose questions about traditional single period hypotheses found in the finance literature.
Contributions of phytoplankton light scattering and cell concentration changes to diel variations in beam attenuation in the equatorial Pacific from flow cytometric measurements of pico-, ultra- and nanoplankton

Abstract The phytoplankton biomass in the equatorial Pacific is dominated by picophytoplankton ( Prochlorococcus , Synechococcus , ∼1 μm diameter) and by mixed populations of ultraphytoplankton (1–2 μm diameter) and nanophytoplankton (2–20 μm, mostly 2–3 μm). The mean forward light scatter of each of these populations, measured on individual cells by flow cytometry, increased during the day and decreased during the night. This pattern was similar to that of bulk red beam attenuation due to particles. In contrast, cell concentration changes did not correspond to the patterns in beam attenuation. Using a combination of empirical calibrations relating beam attenuation to flow cytometric measurements of pure cultures of phytoplankton in the laboratory and Mie theory, we estimated the contributions of different groups of phytoplankton to the diel variations in beam attenuation observed. Our results indicate that the phytoplankton assemblage measured by flow cytometry can account for essentially all of the diel variation in the beam attenuation signal. In most instances nanophytoplankton were the largest contributor to total beam attenuation due to phytoplankton, but ultraphytoplankton usually were more important in determining the diel variations in this property. Prochlorococcus were a smaller but appreciable contributor to beam attenuation changes, and Synechococcus were much less important.
EXPERIMENTAL STUDIES UPON LYMPHOCYTES : II. THE ACTION OF IMMUNE SERA UPON LYMPHOCYTES AND SMALL THYMUS CELLS.

The work of previous investigators gives the impression that it is easy to produce sera which both in vitro and upon injection are leukotoxic. At the same time the specificity of these leukotoxic sera for the particular type of cell used as antigen, and even for leukocytes in general, has been doubtful. The methods used have made certain possible factors of error unavoidable. Even careful washing of an organ or suspension cannot render it wholly blood-free, so that it is not surprising that the sera should be moderately hemolytic and hemagglutinative. Pearce has shown that the injection of very small amounts of blood is sufficient to evoke the production of immune hemolysins. When such sera are injected the lesions, as Pearce states, may be due in part to the production of hemagglutinative thrombi, although this hardly seems to apply to the changes in lymphoid tissue described by Flexner. On the other hand, the lymphotoxic effect of hemolytic sera may be due to the lymphocytes injected with the red cells. Our own experiments indicate that the lymphotoxic and agglutinative factors are to a considerable degree distinct from the hemolytic and hemagglutinative ones, since they can be separated from one another by absorption. Further evidence is presented that the small thymus cells are biologically related to, if not identical with the lymphocytes derived from lymph glands.
Ignition mechanisms of jet-A fuel vapor in a confined environment

Results To present the new method developed here, a sample grid was generated around theNationalAerospace Laboratory- (NLR-)7301 airfoil as shown in Fig. 3. For this grid, the surface clustering was applied by using s1/ C = 0.01 and e = 0.1. The applications of the grid control for the interior domain are also presented. In Fig. 3, the additionally clustered lines in the g direction, the clustered lines in the n direction above the front-half of the airfoil, and the raree ed lines in the n direction above the trailing edge can all be easily observed. In Fig. 4, two grids developed around a cavity are compared. The grid at the left side of the symmetry line (X = 0.0) was obtained without using the marching distance functions. For this grid, grid lines crossed after the 19th g level. The grid at the right side of the symmetry line was produced by using multiple controls in the n direction. The grid line crossings were eliminated, and a controlled interior point distribution was obtained. For both grids, allof the other parameters were exactly the same. For these cavity cases, some local imperfections were removed by applying a simple algebraic smoothing procedure after completion of the hyperbolic grids.
Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling

The cell surface protein Trop2 is expressed on immature stem/progenitor-like cells and is overexpressed in many epithelial cancers. However the biological function of Trop2 in tissue maintenance and tumorigenesis remains unclear. In this study, we demonstrate that Trop2 is a regulator of self-renewal, proliferation, and transformation. Trop2 controls these processes through a mechanism of regulated intramembrane proteolysis that leads to cleavage of Trop2, creating two products: the extracellular domain and the intracellular domain. The intracellular domain of Trop2 is released from the membrane and accumulates in the nucleus. Heightened expression of the Trop2 intracellular domain promotes stem/progenitor self-renewal through signaling via β-catenin and is sufficient to initiate precursor lesions to prostate cancer in vivo. Importantly, we demonstrate that loss of β-catenin or Trop2 loss-of-function cleavage mutants abrogates Trop2-driven self-renewal and hyperplasia in the prostate. These findings suggest that heightened expression of Trop2 is selected for in epithelial cancers to enhance the stem-like properties of self-renewal and proliferation. Defining the mechanism of Trop2 function in self-renewal and transformation is essential to identify new therapeutic strategies to block Trop2 activation in cancer.
Multichannel analyzer featuring ultrahigh stability photometry: application to enzyme determination.

An instrument system has been developed for the simultaneous photometric monitoring of multiple sample channels. Salient features of the system include ultrahigh photometric stability, random access to individual channels, electronic channel selection, wavelength selectivity among the different channels, and either manual or computercontrolled operation. The system implemented in this work consists of 10 sample channels arranged radially around a single stabilized source. It has been evaluated for the kinetic determination of alkaline phosphatase in reconstituted sera. The drift of the photometer averages less than 0.03% T (1.3 x 10-4 A ) per hour. Assay values for alkaline phosphatase exhibit standard deviations of 2% or less in most cases.
Comparison between 1-compartmental and 2-compartmental model in calculation of myocardium blood flow in 82Rb PET imaging

Objective: To the best of our knowledge, no comparison between 1-compartmental (1cm) and 2-compartmental (2cm) models in calculation of myocardium blood flow (MBF) and coronary flow reserve (CFR) in 82 Rb PET imaging has been performed. We present our results of comparing 1cm and 2CM in 82 Rb myocardial PET imaging. Methods: Twenty nine patients, mean age 58±9.5 years (mean±standard deviation), were imaged at rest and pharmaco- logical stress, following an i.v. injection of 1850 MBq of 82 Rb each. A GE DLS PET-CT+16 scanner was used in this study. All images were acquired in 2D mode. For each study, 50 frames were acquired. The time per frame was 5sec between 0-3 min, 15sec between 3-5 min and 30 sec between 5-8 min. MBF was calculated by using 1cm and 2cm. The results for global and regional left circumflex artery (LCX), left anterior artery (LAD) and right coronary artery (RCA), rest and stress MBF, and CFR values obtained by 1cm and 2cm were compared by using Bland and Altman method. The reproducibility coefficient was calculated as 1.96 times the standard deviation (SD) of the differences between 1cm and 2cm values. Results: The global rest MBF values, expressed as mean± SD, for both 1cm and 2cm were very similar (0.74 ± 0.17 vs. 0.73 ± 0.17 mL/min/g), and reproducibility was good, 0.12 mL/min/g (16.3% of the mean). The same held true for the 1CM and 2CM stress global MBF values (1.71 ± 0.54 and 1.73 ± 0.50 mL/min/g) with good reproducibility of 0.25 mL/min/g (14.4% of the mean). The regional, LCX, LAD and RCA rest and stress MBF values, obtained by 1cm and 2cm, were marginally reproducible, i.e., 50% or more of the mean. The global CFR values for both 1cm and 2cm were very similar (2.44 ± 0.84 vs. 0.2.44 ± 0.89), and reproducibility was good 0.34 (14.1% of the mean). Conclusions: The MBF and CFR global rest and stress values obtained by 1cm and 2cm were close and reproducible. However, the regional LAD, RCA and LCX rest and stress MBF values showed marginal reproducibility. Limited regional MBF reproducibility may be caused by sampling error and/or cardiac and breathing motion. We believe that the reproducibility of regional values can be improved by data smoothing and motion gating.
Carbon‐13 NMR spectra of all the isomeric methyl hydroxy‐ and acetoxyoctadecanoates. Determination of chemical shifts by deuterium isotope effects

Carbon-13 NMR spectra of the 17 isomeric methyl hydroxyoctadecanoates and the corresponding acetate derivatives have been measured and chemical shifts assigned to most carbons. Sixteen specifically deuterated hydroxy esters, and their acetates, were employed to make unambiguous assignments from the deuterium isotope effects on the spectra. When substituents are separated from the ends of the chain by 2–3 methylene groups their effects are largely additive. Long range effects of the hydroxyl group were γ, +0.01; δ, −0.09; e, −0.11; ζ, −0.06; η, −0.05; and θ, −0.04 ppm, and of the acetate group were γ, −0.20; δ, −0.20; e, −0.16; ζ, −0.11; η, −0.08 and θ, −0.07 ppm, showing that they extend across seven methylene groups.
Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma.

BACKGROUND: Anti-angiogenesis agents have shown effectiveness in treatment of hepatocellular carcinoma (HCC). It is important to investigate more effective and safe systemic treatment options for patients with advanced HCC. This phase 2 study was designed to determine the efficacy and toxicity of the combination of bevacizumab, capecitabine, and oxaliplatin in patients with advanced unresectable and untransplantable HCC. METHODS: Chemotherapy-naive patients with advanced unresectable and untransplantable HCC were treated with bevacizumab 5 mg/kg and oxaliplatin 130 mg/m2 on day 1 of each cycle, and capecitabine 825 mg/m2 orally twice a day from days 1 to 14 of a 21-day cycle. RESULTS: Forty patients were enrolled to the study, in which 40% had Child-Pugh B disease. Forty percent had an Eastern Cooperative Oncology Group performance status (PS) of 0, 55% had PS of 1, and 5% had PS of 2. Forty percent of patients had hepatitis B virus infection. The median progression-free survival was 6.8 months (95% CI, 3.4-9.1 months), and the median overall survival was 9.8 months (95% CI, 5.2-12.1 months). Eight patients (20%) achieved partial response; 23 patients had stable disease with overall 77.5% disease control rate. The combination was tolerable with limited grade 3/4 toxicity, mainly peripheral neurotoxicity and fatigue. CONCLUSIONS: The combination appeared effective and safe, and the results were encouraging. Further investigation should be considered. Cancer 2011. © 2011 American Cancer Society.
AN ANALYSIS OF ARRHYTHMIAS INDUCED BY OUABAIN IN INTACT DOGS.

The results of this study show that ouabain administration quite often causes idioventricular automaticity to undergo an initial depression and a subsequent enhancement. When the electrocardiogram shows normal sinus rhythm these changes in ventricular automaticity can be unmasked by vagal stimulation which causes either sinus arrest or atrioventricular block. On occasion, the depression of idioventricular automaticity is permanent; if ouabain produces complete atrioventricular block at this time, ventricular arrest ensues. When, on the contrary, the automaticity of Purkinje fibers is progressively enhanced, a stage is reached in which the idioventricular rhythm becomes faster than the sinus rhythm. Eventually the basic ventricular rhythm exhibits pauses during which electrocardio-graphic complexes of different form become apparent. The second class of arrhythmias comprises extrasystoles which may or may not show a constant coupling to sinus beats but which are characterized by a dependence on an initiating beat. It was demonstrated in this investigation that these extra beats appear during slow intravenous administration of ouabain and that they disappear not only on suppression but also on slowing of the sinus rhythm. Furthermore, it was shown that bigeminal rhythm may be transformed into extrasystoles occurring after every second sinus beat by means of vagal stimulation which slows the sinus rate. If, however, the heart was driven at faster rate, several extrasystoles followed one atrial beat. At a more advanced stage of ouabain intoxication these extrasystoles lose their fixed relationship with the sinus beat and runs of self-sustaining tachycardia appear. Such runs of ventricular tachycardia are unaffected by vagal stimulation but have a tendency to subside, spontaneously, and start anew after another initiating sinus beat. If vagal stimulation inhibits the initiating beat, the run of tachycardia also is suppressed. At an advanced stage of intoxication, however, when polymorphic ventricular complexes are present, vagal stimulation no longer produces any apparent effects. Finally, this investigation has shown that, during vagal stimulation which produces sinus arrest or A-V block, atrial fibrillation can be initiated by retrograde transmission of ventricular escape beats even though atrial escape beats are ineffective in eliciting the same phenomenon.
Spatially correlated recruitment of a marine predator and its prey shapes the large‐scale pattern of density‐dependent prey mortality

Patterns of predator dispersal can be critical to the dynamics of prey metapopulations. In marine systems, oceanic currents may shape the dispersal of planktonic larvae of both predators and prey, producing spatial correlations in the recruitment of both species and distinctive geographic patterns of prey mortality. I examined the potential for this phenomenon in two fishes, a wrasse and its grouper predator, at a Caribbean island where the near-shore oceanographic regime produces a temporally consistent spatial pattern of fish recruitment. I found that recruitment and adult abundance of groupers were spatially correlated with recruitment of wrasse prey. Furthermore, the local abundance of predators strongly affected the nature of density-dependent prey mortality. At sites with few predators, wrasse mortality was inversely density-dependent, while mortality was positively density-dependent at sites with higher predator densities. This phenomenon could be important to the dynamics of any metacommunity in which physical forces produce correlated dispersal.
Sparse gamma rhythms arising through clustering in adapting neuronal networks.

Gamma rhythms (30–100 Hz) are an extensively studied synchronous brain state responsible for a number of sensory, memory, and motor processes. Experimental evidence suggests that fast-spiking interneurons are responsible for carrying the high frequency components of the rhythm, while regular-spiking pyramidal neurons fire sparsely. We propose that a combination of spike frequency adaptation and global inhibition may be responsible for this behavior. Excitatory neurons form several clusters that fire every few cycles of the fast oscillation. This is first shown in a detailed biophysical network model and then analyzed thoroughly in an idealized model. We exploit the fact that the timescale of adaptation is much slower than that of the other variables. Singular perturbation theory is used to derive an approximate periodic solution for a single spiking unit. This is then used to predict the relationship between the number of clusters arising spontaneously in the network as it relates to the adaptation time constant. We compare this to a complementary analysis that employs a weak coupling assumption to predict the first Fourier mode to destabilize from the incoherent state of an associated phase model as the external noise is reduced. Both approaches predict the same scaling of cluster number with respect to the adaptation time constant, which is corroborated in numerical simulations of the full system. Thus, we develop several testable predictions regarding the formation and characteristics of gamma rhythms with sparsely firing excitatory neurons.
Evaluating the ability of Bayesian clustering methods to detect hybridization and introgression using an empirical red wolf data set

Bayesian clustering methods have emerged as a popular tool for assessing hybridization using genetic markers. Simulation studies have shown these methods perform well under certain conditions; however, these methods have not been evaluated using empirical data sets with individuals of known ancestry. We evaluated the performance of two clustering programs, baps and structure, with genetic data from a reintroduced red wolf (Canis rufus) population in North Carolina, USA. Red wolves hybridize with coyotes (C. latrans), and a single hybridization event resulted in introgression of coyote genes into the red wolf population. A detailed pedigree has been reconstructed for the wild red wolf population that includes individuals of 50-100% red wolf ancestry, providing an ideal case study for evaluating the ability of these methods to estimate admixture. Using 17 microsatellite loci, we tested the programs using different training set compositions and varying numbers of loci. structure was more likely than baps to detect an admixed genotype and correctly estimate an individual's true ancestry composition. However, structure was more likely to misclassify a pure individual as a hybrid. Both programs were outperformed by a maximum-likelihood-based test designed specifically for this system, which never misclassified a hybrid (50-75% red wolf) as a red wolf or vice versa. Training set composition and the number of loci both had an impact on accuracy but their relative importance varied depending on the program. Our findings demonstrate the importance of evaluating methods used for detecting admixture in the context of endangered species management.
The Effect of Photoresist Outgassing on Boron Clustering and Diffusion in Low Energy BF2+ Ion Implantation

During high current ion implantation into photoresist-covered substrates, evolution of gaseous by-products of photoresist breakdown occurs that can affect the dose control of the process as well as diffusion and activation of the implanted dopants in silicon. The dosimetry effects are well understood and accounted for in modern ion implanter design. In this work, we report on the effect of photoresist outgassing on the distribution of boron concentration in silicon during the subsequent annealing process, boron electrical activation and sheet resistance measurements. Experiments were performed on mono- crystalline and pre-amorphized silicon and oxide covered wafers that help elucidate the mechanism of boron accumulation and diffusion. Higher carbon concentration on the wafer surface due to photoresist outgassing results in boron clustering and reduction of transient enhanced diffusion, leading to higher sheet resistance at low anneal temperature. Implantation through a thin oxide layer can be used to reduce carbon surface contamination and minimize the effects on the boron profiles and sheet resistance.
Impact of spinal cord injury on sexuality: Broad-based clinical practice intervention and practical application

This study focuses on the impact a spinal cord injury may have on achieving physical and emotional intimacy, and potential to maximize sexual ability and quality of life. Spinal cord injury is a traumatic, life-altering event that is usually associated with loss of motor and sensory function, as well as sexual impairment. At the time of injury, the individual is faced with devastating loss and an abundance of new information in a setting of extreme stress and challenge. In the acute rehabilitation setting, there is often a considerable void in providing education and resources regarding sexual concerns and needs. There is a positive relationship between sexual education and sexual activity. The impact of inadequate sexual counseling and education as a part of rehabilitation can be deleterious.
Solution-State (17)O Quadrupole Central-Transition NMR Spectroscopy in the Active Site of Tryptophan Synthase.

Oxygen is an essential participant in the acid-base chemistry that takes place within many enzyme active sites, yet has remained virtually silent as a probe in NMR spectroscopy. Here, we demonstrate the first use of solution-state 17O quadrupole central transition NMR spectroscopy to characterize enzymatic intermediates under conditions of active catalysis. In the 143 kDa pyridoxal-5’-phosphate-dependent enzyme tryptophan synthase, reactions of the α-aminoacrylate intermediate with the nucleophiles indoline and 2-aminophenol correlate with an upfield shift of the substrate carboxylate oxygen resonances. First principles calculations suggest that the increased shieldings for these quinonoid intermediates result from the net increase in the charge density of the substrate-cofactor π bonding network, particularly at the adjacent alpha-carbon site.
Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages

Salmonella enterica serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication of the bacteria depend upon infection of and replication within macrophages, but replication in human macrophages is not widely reported or well studied. In order to assess the ability of Salmonella Typhimurium to replicate in human macrophages, we infected primary monocyte-derived macrophages (MDM) that had been differentiated under conditions known to generate different phenotypes. We found that replication in MDM depends greatly upon the phenotype of the cells, as M1-skewed macrophages did not allow replication, while M2a macrophages and macrophages differentiated with macrophage colony-stimulating factor (M-CSF) alone (termed M0) did. We describe how additional conditions that alter the macrophage phenotype or the gene expression of the bacteria affect the outcome of infection. In M0 MDM, the temporal expression of representative genes from Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2) and the importance of the PhoP/Q two-component regulatory system are similar to what has been shown in mouse macrophages. However, in contrast to mouse macrophages, where replication is SPI2 dependent, we observed early SPI2-independent replication in addition to later SPI2-dependent replication in M0 macrophages. Only SPI2-dependent replication was associated with death of the host cell at later time points. Altogether, our results reveal a very nuanced interaction between Salmonella and human macrophages.
GhostWriter: Using an LSTM for Automatic Rap Lyric Generation

This paper demonstrates the effectiveness of a Long Short-Term Memory language model in our initial efforts to generate unconstrained rap lyrics. The goal of this model is to generate lyrics that are similar in style to that of a given rapper, but not identical to existing lyrics: this is the task of ghostwriting. Unlike previous work, which defines explicit templates for lyric generation, our model defines its own rhyme scheme, line length, and verse length. Our experiments show that a Long Short-Term Memory language model produces better “ghostwritten” lyrics than a baseline model.
Recent Journal and Trade Publication Treatments of Globalization in Mass Media Marketing and Social Change

International marketing strategies, made possible by technological innovation and forced by economic reality, must be supported and refined by empirical study of their successes and failures. This ...
The Norm___ and the Pathological

In this paper, I read The Normal and the Pathological by French philosopher Georges Canguilhem for what it can offer disability theory. I examine how the field has already taken up the text but further, I argue for The Normal and the Pathological as a keystone of disability theory (currently taken up with curiously reserved energy). I start with a precis on the text before offering a condensed citation analysis of the book. In the latter part of the paper, I suggest how the monograph might inform current conversations and I offer possibilities for it to deepen and complicate core notions about disability, including the social model, norms, normalcy, and the normate. I conclude by suggesting that Canguilhem’s philosophical intervention can be understood as "propulsive atavism" – an excavation of medical epistemology in order to map and reconfigure its legacies – and I propose this as one methodological template for disability scholarship.
Understanding and Managing Erectile Dysfunction in Patients Treated for Cancer

Cancer can cause sexual adverse effects by direct and indirect pathways. It can involve sexual organs, indirectly affect body image, or cause fatigue or depression with subsequent effects on libido. Erectile dysfunction (ED), the inability to obtain or maintain an erection firm enough for sexual intercourse, can also result from adverse effects of cancer treatment, such as fatigue, pain, or anxiety about therapy. In addition, depressed feelings about having cancer can affect sexuality, causing a range of signs and symptoms that can lead to ED. Chemotherapy, hormone therapy, surgery, and radiation can all cause sexual adverse effects. Additional factors that play a role include patient age and degree of ED before starting cancer treatment. In this article, we discuss how chemotherapy, hormone therapy, surgery, and radiation affect erectile function as well as possible treatment options for ED.
Assessing Emotional Suffering in Palliative Care: Use of a Structured Note Template to Improve Documentation

Abstract Context Documentation of the emotional or psychological needs of seriously ill patients receiving specialty palliative care is endorsed by the "Measuring What Matters" project as a quality performance metric and recommended for use by hospice and palliative care programs for program improvement. Objectives The aim of this study was to increase the proportion of inpatient palliative care team encounters in which emotional or psychological needs of patients and family members were documented and to qualitatively enrich the nature of this documentation. Methods This is a mixed-methods retrospective study of 200 patient charts reviewed before and after implementation of a structured note template (SmartPhrase) for palliative care encounters. Patterns of documentation of emotional needs pre- and post-implementation were assessed quantitatively and qualitatively using thematic analysis. Results A total of 158 of 200 pre-intervention charts and 185 of 200 post-intervention charts included at least one note from the palliative care team. Documentation of emotional assessment increased after SmartPhrase implementation (63.9% [101 of 158] vs. 74.6% [138 of 185]; P Conclusion A structured note template with a prompt for emotional assessment increases the overall quantity and richness of documentation related to patient and family emotions. However, this documentation remains mostly descriptive. Additional prompting for documentation of recommendations to address identified emotional needs, and the use of screening tools for depression and anxiety, when appropriate, may be necessary for clinically meaningful quality improvements in patient care.
Abstract IA31: Mechanisms of resistance to EGFR inhibitors in lung cancer

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs), including geftinib, erlotinib and afatinib are the standard of care for patients with advanced EGFR mutant non-small cell lung cancer. Treatment with an EGFR TKI leads to a response rate of ~60% and a median progression free survival ranging from 9 to 11 months. Acquired drug resistance inevitably develops in most of not all EGFR mutant lung cancer patients treated with EGFR inhibitors. The most common mechanism of acquired resistance is the development of a secondary EGFR T790M mutation. Other mechanism of resistance include activation of bypass signaling pathways (such as MET or HER2) and histological transformation. Over the last few years a series of new structurally distinct EGFR inhibitors have been identified and entered the clinic that are capable of inhibiting EGFR T790M. This class of mutant selective EGFR TKIs are effective both against the activating EGFR mutation and the drug resistant T790M but spare inhibition of wild type (WT) EGFR. This has enormous potential therapeutic implications as the side effects of all approved EGFR inhibitors is derived from inhibition of WT EGFR. Several of these agents, including AZD9291 and rociletinib (CO-1686) are in advanced stage clinical development. Both agents have been granted FDA’s breakthrough designation. In EGFR inhibitor resistant patients who have developed resistance to current clinical EGFR inhibitors through T790M, the response rates to either AZD9291 or rociletinib is over 60% with median progression free survivals of ~ 10 months. Current research efforts and clinical studies are focusing on a.) understanding mechanisms of drug resistance to this new class of EGFR inhibitors, b.) the development of rationale combination therapies and c.) use of these agents as initial treatment (instead of currently approved EGFR inhibitors) for patients with advanced EGFR mutant NSCLC. Citation Format: Pasi Janne. Mechanisms of resistance to EGFR inhibitors in lung cancer. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA31.
Antibody–Antigen Recognition and Conformational Changes

Publisher Summary Antibodies are malleable molecules that can vary in both their sequence and structure in order to recognize an infinite number of potential antigens. Structural studies of these molecules have led to a better understanding of their mechanism of action, and allowed for improvements on their natural design so as to produce antibodies that are useful in many fields such as catalytic antibodies, and as human therapeutics. The antigens recognized by these antibodies include small haptens, peptides, DNA, carbohydrate, protein, and viruses. Some of the antibodies are of chemical or medical importance, such as those that catalyze chemical reactions Approved therapeutic antibodies are also available to treat diseases, such as cancer, arthritis, asthma, and psoriasis, and to address problems with transplant rejection and blood clotting. In addition, studies of rare, broadly neutralizing HIV-1 antibodies with unique methods of antigen recognition have uncovered new strategies for viral neutralization, thus leading to novel ideas for future vaccine design. This wealth of structural information has proven invaluable in the fields of antibody engineering and catalytic antibody generation, and in the development of effective antibody-based drug therapies.
On the effects of boundary-layer transition on a cylindrical afterbody at incidence in low-speed flow

The experimentally observed changes in the location of boundary layer separation on the cylindrical afterbody of a tangent-ogive-cylinder, placed at incidence in a uniform flow, are related to the phenomenon of laminar-turbulent transition. Existing knowledge of the transition mechanisms which operate in general, three-dimensional; boundary layers, is described and simple prediction criteria are derived for this configuration. These criteria are compared with the currently available empirical methods for the prediction of critical Reynolds numbers for such flows. It is demonstrated that the methods which have been published to date are incomplete and the accompanying analyses are based upon superficial and erroneous physical arguments. The implications of boundary layer transition on the normal forces generated by a cylindrical afterbody are also discussed. Finally, the possibility of using transition fixing to establish ‘high Reynolds number’ separated flows in ‘low Reynolds number’ wind-tunnel facilities is briefly considered.
Fall motion detection using combined range and Doppler features

Feature selection based on combined Doppler and range information improves fall detection and enables better discrimination against similar high Doppler non-rhythmic motions, such as sitting. A fall is typically characterized by an extension in range beyond that associated with sitting, which is determined by the seat horizontal depth. In this paper, we demonstrate, using time-frequency (TF) spectrograms, that range-Doppler radar plays a fundamental and important role in motion classification for assisted living applications. It reduces false alarms along with the associated cost in the unnecessary deployment of the first responders. This reduction is considered vital for the development of in-home radar monitoring and for casting it as a viable technology for aging-in-place.
Physics in 2116: Physicists Create Closed Time-like Curves

This is an entry for Physics Today's recent essay contest, written as a "Search and Discovery" news story, imagining what major breakthroughs might be shaking the physics world one hundred years from now.
Signaling Lymphocytic Activation Molecule Family Member 7 Engagement Restores Defective Effector CD8+ T Cell Function in Systemic Lupus Erythematosus

Objective: Effector CD8+ T cell function is impaired in SLE and associated with compromised ability to fight infections. SLAMF7 engagement has been shown to enhance NK cell degranulation. Thus, we characterized the expression and function of SLAMF7 on CD8+ T cells subsets isolated from peripheral blood of SLE patients and healthy subjects. Methods: CD8+ T cell subset distribution, SLAMF7 expression and cytolytic enzyme expression (perforin, GzmA, GzmB) were monitored on cells isolated from SLE patients and healthy controls by flow cytometry. CD107a expression and IFNγ production in response to viral antigenic stimulation were assessed by flow cytometry in the presence or absence of an anti-SLAMF7 antibody. The antiviral cytotoxic activity in response to SLAMF7 engagement was determined using a flow cytometry-based assay. Results: The distribution of CD8+ T cell subsets is altered in the peripheral blood of SLE patients with decreased effector cell subpopulation. Memory CD8+ T cells from SLE patients display decreased amounts of SLAMF7, a surface receptor that characterizes effector CD8+ T cells. Ligation of SLAMF7 increases CD8+ T cell degranulation capacity and the percentage of IFNγ-producing cell in response to antigen challenge in SLE and healthy controls. Moreover, SLAMF7 engagement promotes cytotoxic lysis of target cells in response to viral antigenic stimulation. Conclusion: Activation of SLAMF7 through a specific mAb restores defective SLE effector CD8+ T cells function in response to viral antigens and represents a potential therapeutic option in SLE. This article is protected by copyright. All rights reserved.
Consumer intentions to falsify personal information online: unethical or justifiable?

ABSTRACTCompanies routinely analyse the online activities of consumers to understand shopping habits and buying patterns. As the amount of personal information available online has grown, so has the potential for its misuse. When consumers believe that their personal information is being used for an unstated purpose, they may consider the firm to be acting unethically. They may then falsify their personal information online as a reaction to apparent ethical violations by companies or as an opportunistic unethical act of their own. The purpose of the present research is to propose a framework that could be used to understand consumer intentions to falsify personal information online. The research is important from both a theoretical and business perspective. From a theoretical standpoint, they add to the literature on the dark side of marketing by examining ethically questionable behaviour by consumers. The research is relevant for firms because when consumers falsify personal information their ability to ...
MicroRNA-Related Genetic Variants Associated with Survival of Head and Neck Squamous Cell Carcinoma

Background: Head and neck squamous cell carcinoma (HNSCC) is commonly diagnosed at an advanced stage, and prognosis for such patients is poor. There remains a gap in our understanding of genetic variants related with HNSCC prognosis. miRNA-related single nucleotide polymorphisms (miR-SNPs) are a class of genetic variants with gene-regulatory potential. Methods: We used a genome-scale approach and independent patient populations in a two-stage approach to test 40,286 common miR-SNPs for association with HNSCC survival in the discovery population (n = 847), and selected the strongest associations for replication in validation phase cases (n = 1,236). Furthermore, we leveraged miRNA interaction databases and miRNA expression data from The Cancer Genome Atlas, to provide functional insight for the identified and replicated associations. Results: Joint population analyses identified novel miR-SNPs associated with overall survival in oral and laryngeal cancers. rs1816158, located within long noncoding RNA MIR100HG, was associated with overall survival in oral cavity cancer (HR, 1.56; 95% confidence interval (CI), 1.21–2.00). In addition, expression of MIR100HG-embedded miRNA, miR-100, was significantly associated with overall survival in an independent cohort of HNSCC cases (HR, 1.25; 95% CI, 1.06–1.49). A SNP in the 3′UTR of SH3BP4 (rs56161233) that overlaps predicted miRNA-binding sites and is predicted to disrupt several miRNA–mRNA interactions was associated with overall survival of laryngeal cancer (HR, 2.57; 95% CI, 1.71–3.86). Conclusions: This work reveals novel miR-SNPs associated with HNSCC survival, and utilizes miRNA-mRNA interaction and expression data to provide functional support for these associations. Impact: These findings extend our understanding of how genetic variation contributes to HNSCC survival, and may contribute to future prognostic models for improved risk stratification.