gebhart/patrepeval huggingface dataset:
Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs (2016)

The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds. Antinociception was assessed using an electronic von Frey (vF) device as a mechanical/pressure model. Acetaminophen was administered at a dose of 600 mg (14.4-23.1 mg/kg) and codeine phosphate at 90 mg (2.1-3.3 mg/kg) equivalent to 67.5 mg codeine base (1.6-2.5 mg/kg). The geometric mean maximum plasma concentrations of acetaminophen, codeine, and codeine-6-glucuronide were 7.95 μg/mL, 11.0 ng/mL, and 3819 ng/mL, respectively. Morphine concentrations were <1 ng/mL. The terminal half-lives of acetaminophen, codeine, and codeine-6-glucuronide were 0.94, 1.71, and 3.12 h. There were no significant changes in vF thresholds, except at 12 h which decreased on average by 17% compared to baseline. The decrease in vF thresholds at 12 h could be due to aversion, hyperalgesia, or random variability. The lack of antinociception in this study could be due to a true lack of antinociception, lack of model sensitivity, or specificity. Further studies using different models (including clinical trials), different dog breeds, multiple dose regimens, and a range of dosages are needed prior to recommended use or concluding lack of efficacy for oral acetaminophen/codeine in dogs.
Maximum likelihood image identification and restoration based on the EM algorithm (2003)

Summary form only given. Simultaneous iterative identification and restoration have been treated. The image and the noise have been modeled as multivariate Gaussian processes. Maximum-likelihood estimation has been used to estimate the parameters that characterize the Gaussian processes, where the estimation of the conditional mean of the image represents the restored image. Likelihood functions of observed images are highly nonlinear with respect to these parameters. Therefore, it is in general very difficult to maximize them directly. The expectation-maximization (EM) algorithm has been used to find these parameters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Formation of Micrometer Scale Metal Structures on Glass by Selective Electroless Plating on Photopatterned Titanium and Copper Containing Films (2017)

A procedure for formation of catalytic SiO<sub>2</sub> substrate adhesive layer patterns and selective electrochemical metal deposition on the catalyst images was investigated. A photoreactive solution containing a diazonaphthoquinone sulfonate ester and Ti and Cu complexes was developed to deposit Cu catalyst-TiO<sub>2</sub> adhesive layer latent images on glass. Sub-micrometer/micrometer scale positive tone photoactive TiCu complex film patterns were formed using a conventional photolithography technique. The Cu ions in 40-50 nm thick Ti and Cu oxide layers formed by pyrolysis of the TiCu complex films were reduced, residual Cu displaced with Pd then the porous Ti oxide structure filled and plated with Cu by selective electroless then electrolytic plating. Annealing the Cu plating filled TiO<sub>2</sub> layers on glass resulted in formation of a smooth Ti<sup>3+</sup>/Cu<sup>1+</sup> oxide interface that enabled formation of 20 μm thick Cu deposits on glass substrate with up to 1 kN/m adhesion strength. The adhesion strength was attributed to chemical bonding of Ti<sup>3+</sup> and Cu<sup>1+</sup> oxides to the glass and Ti<sup>4+</sup> oxide to the Cu plating that was formed upon annealing the Cu filled TiO<sub>2</sub> interlayer. Furthermore, a dip coating procedure was adapted that allowed copper film deposition on the entire surface of a 300 μm thick glass substrate with 50 μm in diameter holes enabling formation of electrically conductive through glass substrate interconnects.
The NMR–Rosetta capsid model of M13 bacteriophage reveals a quadrupled hydrophobic packing epitope (2015)

Filamentous phage are elongated semiflexible ssDNA viruses that infect bacteria. The M13 phage, belonging to the family inoviridae, has a length of ∼1 μm and a diameter of ∼7 nm. Here we present a structural model for the capsid of intact M13 bacteriophage using Rosetta model building guided by structure restraints obtained from magic-angle spinning solid-state NMR experimental data. The C5 subunit symmetry observed in fiber diffraction studies was enforced during model building. The structure consists of stacked pentamers with largely alpha helical subunits containing an N-terminal type II β-turn; there is a rise of 16.6-16.7 Å and a tilt of 36.1-36.6° between consecutive pentamers. The packing of the subunits is stabilized by a repeating hydrophobic stacking pocket; each subunit participates in four pockets by contributing different hydrophobic residues, which are spread along the subunit sequence. Our study provides, to our knowledge, the first magic-angle spinning NMR structure of an intact filamentous virus capsid and further demonstrates the strength of this technique as a method of choice to study noncrystalline, high-molecular-weight molecular assemblies.
Continuous Modulation of Electrode Work Function with Mixed Self-Assembled Monolayers and Its Effect in Charge Injection (2009)

Self-assembled monolayers (SAMs) of binary mixtures of n-decanethiol and the fluorinated analogue (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanethiol) were formed on silver surface. The film structure was characterized by reflection absorption IR and XPS to be a homogeneous mixture of the two components. The mixed monolayers serve to tune the work function of silver over a wide range by varying the surface composition of the mixed monolayer from 4.1 to 5.8 eV. The mixed SAM-modified Ag surfaces were used as the anode in the fabrication of hole-only devices with the device structure Ag/SAM/HTL/Ag, where HTL represents a hole-transporting layer. It is shown that depending on the HTL used and thus the HOMO level involved, the maximum current injection into the device occurred with differently modified Ag. Top-emitting organic light-emitting diodes fabricated with differently modified silver electrodes showed that the maximum current and maximum luminance efficiency occur at anodes of different modifications due to a change in the hole-electron charge balance.
Human choriocarcinomas: Placental growth factor-dependent preclinical tumor models (2011)

Choriocarcinomas are a rare form of cancer that develops in the uterus from tissue which would normally become the placenta. Choriocarcinomas are a trophoblastic gestational disease and have been studied largely to investigate conditions related to pregnancy such as preeclampsia. Choriocarcinomas are highly angiogenic and produce high levels of placental growth factor (PlGF) to promote the development of blood vessels. Upregulation of PlGF expression also occurs during the development of other human malignancies such as breast cancer and melanoma. Both tumor specimens and plasma samples have higher levels of PlGF than normal tissues. Hence, PlGF has emerged as a valid target for anti-angiogenic therapy. The cell lines BeWo, JAR and JEG-3, derived from human choriocarcinomas, were investigated in vitro and in vivo for suitability as PlGF-dependent models. BeWo, JAR and JEG-3 cells were characterized in culture and were implanted into immunodeficient mice to generate subcutaneous tumors. The PlGF and VEGF angiogenic profiles of the choriocarcinoma cells and tumors were investigated by ELISA and by immunohistochemical methods. Double immunofluorescence methods were applied to choriocarcinoma xenograft sections to characterize the cellular components of the blood vessels. sFLT01, a fusion protein that neutralizes PlGF, was assessed in cell culture experiments and xenograft studies. The novel results presented here validate the importance of human choriocarcinoma cell lines and xenografts in further exploring the role of PlGF in tumor angiogenesis, for evaluating PlGF as an anti-angiogenic target, and for developing therapies that may provide clinical benefit.
Determination of Substrate Preferences for Desaturases and Elongases for Production of Docosahexaenoic Acid from Oleic Acid in Engineered Canola (2017)

Production of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plant seed oils has been pursued to improve availability of these omega-3 fatty acids that provide important human health benefits. Canola (Brassica napus), through the introduction of 10 enzymes, can convert oleic acid (OLA) into EPA and ultimately DHA through a pathway consisting of two elongation and five desaturation steps. Herein we present an assessment of the substrate specificity of the seven desaturases and three elongases that were introduced into canola by expressing individual proteins in yeast. In vivo feeding experiments were conducted with 14 potential fatty acid intermediates in an OLA to DHA pathway to determine the fatty acid substrate profiles for each enzyme. Membrane fractions were prepared from yeast expression strains and shown to contain active enzymes. The elongases, as expected, extended acyl-CoA substrates in the presence of malonyl-CoA. To distinguish between enzymes that desaturate CoA- and phosphatidylcholine-linked fatty acid substrates, we developed a novel in vitro method. We show that a delta-12 desaturase from Phytophthora sojae, an omega-3 desaturase from Phytophthora infestans and a delta-4 desaturase from Thraustochytrium sp., all prefer phosphatidylcholine-linked acyl substrates with comparatively low use of acyl-CoA substrates. To further validate our method, a delta-9 desaturase from Saccharomyces cerevisiae was confirmed to use acyl-CoA as substrate, but could not use phosphatidylcholine-linked substrates. The results and the assay methods presented herein will be useful in efforts to improve modeling of fatty acid metabolism and production of EPA and DHA in plants.
Theoretical and experimental determination of steering mechanism for Risley prism systems (2013)

Two different analytical methods, the first-order paraxial approximation method and the nonparaxial ray tracing method, are applied to determine the steering mechanism of the Risley prism system, including the pointing prediction and the complete and exact inverse orientation solutions. The analytical results obtained with the two different methods are investigated in detail about the pointing prediction and the two groups of inverse orientation solutions, respectively. Risley prism equipment for wide angular range beam scanning is assembled and the experimental setup is built to test the steering mechanism of the Risley prism system. Experimental results validate the availability of the nonparaxial ray tracing method to discuss the beam steering mechanism for the Risley prism system.
Effects of Inhaled Lidocaine on Exercise-Induced Asthma (1987)

Experiments were performed to determine if stimulation of afferent nerve endings in the respiratory mucosa plays a major role in the initiation of exercise-induced asthma. Five asthmatic subjects were studied in two sessions of 10 min treadmill exercise using an identical workload. In the control session the subjects were exercised without treatment; in the other session aerosol lidocaine (1.5 mg/kg) was inhaled from residual volume to total lung capacity before exercise was started. Pulmonary function tests were measured (1) to obtain baseline values before the aerosol inhalation or exercise was commenced, (2) 2-3 min after completion of lidocaine inhalation, and (3) 4 min after termination of exercise. In the control session the mean postexercise forced expiratory volume in 1 s (FEV1) and the mean forced expiratory flow during the middle half of forced vital capacity (FEF25-75%) were decreased to 61 and 44% of the baseline values, respectively. Similarly, with the lidocaine treatment the post-exercise FEV1 and FEF25-75% were decreased to 54 and 44% of the baseline values, respectively. These data indicate that the afferent nerves in the respiratory mucosa may not play a critical role in the development of exercise-induced asthma.
Enantiodivergent Synthesis of Both Enantiomers of Gypsy Moth Pheromone Disparlure (2007)

Enantiodivergent synthesis of both (-)- and (+)-disparlure, a bioactive pheromone, possessing a cis-epoxide has been accomplished. The key step involves the cross metathesis of a chiral homoallylic alcohol derived from l-(+)-tartaric acid.
Antibody Conjugation Approach Enhances Breadth and Potency of Neutralization of Anti-HIV-1 Antibodies and CD4-IgG (2013)

Broadly neutralizing antibodies PG9 and PG16 effectively neutralize 70 to 80% of circulating HIV-1 isolates. In this study, the neutralization abilities of PG9 and PG16 were further enhanced by bioconjugation with aplaviroc, a small-molecule inhibitor of virus entry into host cells. A novel air-stable diazonium hexafluorophosphate reagent that allows for rapid, tyrosine-selective functionalization of proteins and antibodies under mild conditions was used to prepare a series of aplaviroc-conjugated antibodies, including b12, 2G12, PG9, PG16, and CD4-IgG. The conjugated antibodies blocked HIV-1 entry through two mechanisms: by binding to the virus itself and by blocking the CCR5 receptor on host cells. Chemical modification did not significantly alter the potency of the parent antibodies against nonresistant HIV-1 strains. Conjugation did not alter the pharmacokinetics of a model IgG in blood. The PG9-aplaviroc conjugate was tested against a panel of 117 HIV-1 strains and was found to neutralize 100% of the viruses. PG9-aplaviroc conjugate IC50s were lower than those of PG9 in neutralization studies of 36 of the 117 HIV-1 strains. These results support this new approach to bispecific antibodies and offer a potential new strategy for combining HIV-1 therapies.
Development of a new method for the determination of thyroxine in serum based on isotope dilution gas chromatography mass spectrometry (1994)

A new gas chromatographic/mass spectrometric method in combination with isotope dilution for the determination of thyroxine in serum is described. Special attention was paid to the methylation step of thyroxine, which was investigated using methanolic HCl, dimethylformamide/dimethylacetal and diazomethane, the latter giving the best results in terms of reproducible isotope ratios. For internal standardization, (13C6)-thyroxine was dissolved in fraction V human albumin solution (70 g l-1). The internal standard-in-albumin solution was mixed with known amounts of thyroxine standard, dissolved in 0.05 M Na2HPO4 buffer at pH 11.6, to give isotope ratios of 0.75, 1.00 and 1.25. The same internal standard solution was also used for isotope dilution of the unknown serum samples. The volume of serum was adapted to give a 1:1 isotope ratio. Sample pretreatment consisted of protein precipitation and a two-step liquid/liquid extraction procedure. After methylation of unlabelled and labelled thyroxine with diazomethane and perfluoroacylation with pentafluoropropionic anhydride and heptafluorobutyric anhydride, respectively, mass spectrometric monitoring was done at m/z 951/957 and 1001/1007. Quantitative determination of thyroxine in five serum samples in duplicate, during three consecutive days, showed a mean overall imprecision of 1.0% and a deviation of +0.4% from the target value as determined by a definitive method.
Targeting PI3K/Akt/mTOR Signaling in Cancer (2014)

The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways are two pathways crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions (e.g., cancer). Indeed, they are so interconnected that, in a certain sense, they could be regarded as a single, unique pathway. In this paper, after a general overview of the biological significance and the main components of these pathways, we address the present status of the development of specific PI3K, Akt, and mTOR inhibitors, from already registered medicines to novel compounds that are just leaving the laboratory bench.
Impact of Group-II Acceptors on the Electrical and Optical Properties of GaN (2013)

We explore the properties of group-II acceptors in GaN by performing hybrid density functional calculations. We find that Mg Ga gives rise to hole localization in zinc-blende GaN, similar to the behavior in the wurtzite phase. Alternative acceptor impurities, such as Zn and Be, also lead to localized holes in wurtzite GaN, and their ionization energies are larger than that of Mg. All these group-II acceptors also cause large lattice distortions in their neutral charge state, which in turn lead to deep and broad luminescence signals. We explore the consequences of these results for p-type doping.
Comparison of two‐dimensional and three‐dimensional simulations of dense nonaqueous phase liquids (DNAPLs): Migration and entrapment in a nonuniform permeability field (2005)

The influence of reduced dimensionality (two‐dimensional (2‐D) versus 3‐D) on predictions of dense nonaqueous phase liquid (DNAPL) infiltration and entrapment in statistically homogeneous, nonuniform permeability fields was investigated using the University of Texas Chemical Compositional Simulator (UTCHEM), a 3‐D numerical multiphase simulator. Hysteretic capillary pressure–saturation and relative permeability relationships implemented in UTCHEM were benchmarked against those of another lab‐tested simulator, the Michigan‐Vertical and Lateral Organic Redistribution (M‐VALOR). Simulation of a tetrachloroethene spill in 16 field‐scale aquifer realizations generated DNAPL saturation distributions with approximately equivalent distribution metrics in two and three dimensions, with 2‐D simulations generally resulting in slightly higher maximum saturations and increased vertical spreading. Variability in 2‐D and 3‐D distribution metrics across the set of realizations was shown to be correlated at a significance level of 95–99%. Neither spill volume nor release rate appeared to affect these conclusions. Variability in the permeability field did affect spreading metrics by increasing the horizontal spreading in 3‐D more than in 2‐D in more heterogeneous media simulations. The assumption of isotropic horizontal spatial statistics resulted, on average, in symmetric 3‐D saturation distribution metrics in the horizontal directions. The practical implication of this study is that for statistically homogeneous, nonuniform aquifers, 2‐D simulations of saturation distributions are good approximations to those obtained in 3‐D. However, additional work will be needed to explore the influence of dimensionality on simulated DNAPL dissolution.
Optical properties of zinc-blende CdSe and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Zn</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="italic">x</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Cd</mml:mi></mml:mrow><mml:mrow><mml:mn>1</mml:mn><mml:mi mathvariant="normal">−</mml:mi><mml:mi mathvariant="italic">x</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math>Se films grown on GaAs (1994)

We present room-temperature ellipsometric measurements of the dielectric function of ${\mathrm{Zn}}_{\mathit{x}}$${\mathrm{Cd}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$Se single-crystal films grown on (001)GaAs in the 1.5--6.0-eV energy region x ranging from 0 to 1. We identify the ${\mathit{E}}_{0}$, ${\mathit{E}}_{0}$+${\mathrm{\ensuremath{\Delta}}}_{0}$, ${\mathit{E}}_{1}$, ${\mathit{E}}_{1}$+${\mathrm{\ensuremath{\Delta}}}_{1}$, and ${\mathit{E}}_{2}$ threshold energies using the CdSe band structure calculated with a nonlocal empirical pseudopotential method. We find that the contact exciton effect has to be included in the calculated dielectric function of CdSe in order to obtain good agreement with our measurements. A compositon-dependent critical-point analysis of the ${\mathit{E}}_{1}$ and ${\mathit{E}}_{1}$+${\mathrm{\ensuremath{\Delta}}}_{1}$ structures has been performed. We also find that the spin-orbit-splitting band gap ${\mathrm{\ensuremath{\Delta}}}_{1}$(x), the linewidths, and the excitonic angles are about maximum at x=0.5, which we attribute to the statistical fluctuation of the alloy composition. Finally, the ${\mathit{E}}_{1}$ and ${\mathit{E}}_{1}$+${\mathrm{\ensuremath{\Delta}}}_{1}$ critical-point amplitudes cannot be understood by the one-electron approximation, confirming the existence of strong excitonic effects.
Forecasting time series with complex seasonal patterns using exponential smoothing (2022)

A new innovations state space modeling framework, incorporating Box-Cox transformations, Fourier series with time varying coefficients and ARMA error correction, is introduced for forecasting complex seasonal time series that cannot be handled using existing forecasting models. Such complex time series include time series with multiple seasonal periods, high frequency seasonality, non-integer seasonality and dual-calendar effects. Our new modelling framework provides an alternative to existing exponential smoothing models, and is shown to have many advantages. The methods for initialization and estimation, including likelihood evaluation, are presented, and analytical expressions for point forecasts and interval predictions under the assumption of Gaussian errors are derived, leading to a simple, comprehensible approach to forecasting complex seasonal time series. Our trigonometric formulation is also presented as a means of decomposing complex seasonal time series, which cannot be decomposed using any of the existing decomposition methods. The approach is useful in a broad range of applications, and we illustrate its versatility in three empirical studies where it demonstrates excellent forecasting performance over a range of prediction horizons. In addition, we show that our trigonometric decomposition leads to the identification and extraction of seasonal components, which are otherwise not apparent in the time series plot itself.
Gravity gradiometer survey errors (1988)

Abstract Gradiometer system noise, sampling effects, downward continuation, and limited data extent are the important contributors to moving-base gravity gradiometer survey error. We apply a two-dimensional frequency-domain approach in simulations of several sets of airborne survey conditions to assess the significance of the first two sources. A special error allocation technique is used to account for the downward continuation and limited extent effects. These two sources cannot be modeled adequately as measurement noise in a linear error estimation algorithm.For a typical characterization of the Earth's gravity field, our modeling indicates that limited data extent generally contributes about one-half of the total error variance associated with recovery of the gravity disturbance vector at the Earth's surface; gradiometer system noise typically contributes about one-third. However, sampling effects are also very important (and are controlled through the survey track spacing). A 5 km track spacing provides a reasonable tradeoff between survey cost and errors due to track spacing. Furthermore, our results indicate that a moving-base gravity gradiometer system can recover each component of the gravity disturbance vector with an rms accuracy better than 1.0 mGal.
High precision subsurface photodisruption in human sclera (2002)

High precision, subsurface scleral photodisruption can be achieved in vitro for a variety of intrascleral incisions. Further studies are required to determine if this technique is applicable in vivo for actual surgical applications.