gebhart/patrepeval huggingface dataset:
Pharmacodynamic Target Evaluation of a Novel Oral Glucan Synthase Inhibitor, SCY-078 (MK-3118), Using an <i>In Vivo</i> Murine Invasive Candidiasis Model (2014)

Echinocandins inhibit the synthesis of β-1,3-D-glucan in Candida and are the first-line therapy in numerous clinical settings. Their use is limited by poor oral bioavailability, and they are available only as intravenous therapies. Derivatives of enfumafungin are novel orally bioavailable glucan synthase inhibitors. We performed an in vivo pharmacodynamic (PD) evaluation with a novel enfumafungin derivative, SCY-078 (formerly MK-3118), in a well-established neutropenic murine model of invasive candidiasis against C. albicans, C. glabrata, and C. parapsilosis. The SCY-078 MICs varied 8-fold. Oral doses of 3.125 to 200 mg/kg SCY-078 salt in sterile water produced peak levels of 0.04 to 2.66 μg/ml, elimination half-lives of 5.8 to 8.5 h, areas under the concentration-time curve from 0 to 24 h (AUC0-24 h) of 0.61 to 41.10 μg·h/ml, and AUC from 0 to infinity (AUC0-∞) values of 0.68 to 40.31 μg·h/ml. The pharmacokinetics (PK) were approximately linear over the dose range studied. Maximum response (Emax) and PK/PD target identification studies were performed with 4 C. albicans, 4 C. glabrata, and 3 C. parapsilosis isolates. The PD index AUC/MIC was explored by using total (tAUC) and free (fAUC) drug concentrations. The maximum responses were 4.0, 4.0, and 4.3 log10 CFU/kidney reductions for C. albicans, C. glabrata, and C. parapsilosis, respectively. The AUC/MIC was a robust predictor of efficacy (R2, 0.53 to 0.91). The 24-h PD targets were a static dose of 63.5 mg/kg, a tAUC/MIC of 500, and an fAUC/MIC of 1.0 for C. albicans; a static dose of 58.4 mg/kg, a tAUC/MIC of 315, and an fAUC/MIC of 0.63 for C. glabrata; and a static dose of 84.4 mg/kg, a tAUC/MIC of 198, and an fAUC/MIC of 0.40 for C. parapsilosis. The mean fAUC/MIC values associated with a 1-log kill endpoint against these species were 1.42, 1.26, and 0.91 for C. albicans, C. glabrata, and C. parapsilosis, respectively. The static and 1-log kill endpoints were measured relative to the burden at the start of therapy. The static and 1-log kill doses, as well as the total and free drug AUC/MIC PD targets, were not statistically different between species but were numerically lower than those observed for echinocandins. SCY-078 is a promising novel oral glucan synthase inhibitor against Candida species, and further investigation is warranted.
Radiance and photon noise: imaging in geometrical optics, physical optics, quantum optics and radiology (2016)

The statistics of detector outputs produced by an imaging system are derived from basic radiometric concepts and definitions. We show that a fundamental way of describing a photon-limited imaging system is in terms of a Poisson random process in spatial, angular, and wavelength variables. We begin the paper by recalling the concept of radiance in geometrical optics, radiology, physical optics, and quantum optics. The propagation and conservation laws for radiance in each of these domains are reviewed. Building upon these concepts, we distinguish four categories of imaging detectors that all respond in some way to the incident radiance, including the new category of photon-processing detectors (capable of measuring radiance on a photon-by-photon basis). This allows us to rigorously show how the concept of radiance is related to the statistical properties of detector outputs and to the information content of a single detected photon. A Monte-Carlo technique, which is derived from the Boltzmann transport equation, is presented as a way to estimate probability density functions to be used in reconstruction from photon-processing data.
Physiology and Pathophysiology of Renal Aquaporinsa (1999)

The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. AQP2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated trafficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Importantly, multiple studies have now identified a critical role of AQP2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP4 are basolateral water channels located in the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.
Metal-Enhanced Fluorescence of Chlorophylls in Single Light-Harvesting Complexes (2007)

Ensemble and single-molecule spectroscopy demonstrates that both emission and absorption of peridinin-chlorophyll-protein photosynthetic antennae can be largely enhanced through plasmonic interactions. We find up to 18-fold increase of the chlorophyll fluorescence for complexes placed near a silver metal layer. This enhancement, which leaves no measurable effects on the protein structure, is observed when exciting either chlorophyll or carotenoid and is attributed predominantly to an increase of the excitation rate in the antenna. The enhancement mechanism comes from plasmon-induced amplification of electromagnetic fields inside the complex. This result is an important step toward applying plasmonic nanostructures for controlling the optical response of complex biomolecules and improving the design and functioning of artificial light-harvesting systems.
DEVELOPMENT OF HIGH VOLUME REDUCTION AND CEMENT SOLIDIFICATION TECHNIQUE FOR PWR CONCENTRATED WASTE (2001)

The hyper-Cement solidification technique was developed, which reduced the volume of concentrated liquid wastes from PWR plant by means of stable cement solidification. Drying the liquid wastes into powder using a wiped film evaporator and then solidifying the large amount of powdered wastes attained high volume reduction of the wastes due to the special cement paste with low viscosity. Using this technique, The volume reduction ratio of the wastes of was larger than in the case of using bitumen technique, which is conventionally employed to solidify the concentrated liquid wastes in PWR plant. This paper presents the outline of the hyper-cement technique and discusses the mechanical and chemical properties of the cement solidification. INTRODUCTION Cement materials are known to be attractive for solidifying radioactive wastes because of its low water permeability after hardening and the high absorbability of some radioactive species onto hardening materials. In view of the simplicity of the solidification process using these materials , cement solidification systems are operating at many nuclear facilities. However, its hardening is sometimes hindered by the presence of certain components such as boric acid and phosphate acid because they impair the hydration reactions of cement. These impairments are of particular concern in the case of the solidification of concentrated liquid wastes from pressurized water reactor (PWRs), since their main components is boric acid. To avoid these impairments, it is necessary to reduce the amount of these components in cement solidification, but this causes the increase of the volume of the products of waste solidification. F or this reason, the bitumen technique in which both salts of boric compounds and radioactive elements are mixed into molten asphalt is introduced to reduce the generation of the products of waste solidification in PWR power plants. But this solidification process is complicated and sometimes it is necessary to repair equipment because the activation of molten asphalt at high temperature results in the corrosion of metals. Thus, there is a need to develop a s olidification technique using cement materials that increases the borate content in products. We have already developed a new cement solidification technique that realizes high volume reduction of waste. This technique consists of two processes: a dryin g process to reduce the volume of liquid waste, and a cementation process to solidify a large amount of the dried product with a given cement. Using this technique, The volume reduction ratio of the wastes was larger than that in the case of using the bitumen technique. This paper presents the outline of a new cement solidification technique for concentrated liquid waste generated from PWR power plants and investigates the detailed properties of the products solidified by the technique.
Solubility in binary mixtures at the immiscibility critical point (1987)

Abstract It is shown that the solubility of organic solids in binary mixtures of partially miscible liquids is singular at the immiscibility critical point. The theoretically predicted maximum of solubility in the vicinity of the critical point is found experimentally. The effect is similar to the phenomenon observed near the gas‐liquid critical point. The similarity of these two critical phenomena may have interesting technical applications and may provide guidelines for identifying promising new solvents for separation processes.
Molecular Transduction in Smell and Taste (1988)

In this paper we describe recent progress in our understanding of the molecular mechanism of smell and taste. Such new insight highlights the similarity of olfaction and gustation to another molecular sensory mechanism-visual photoreception. It also underlines the homology of recognition and transduction events in smell and taste with those that take place in hormone and neurotransmitter reception (Figs. 1 and 2) (Lancet and Pace 1987). An important theme in the present paper is the possibility that although the chemosensory cells utilize a molecular transduction apparatus akin to that of other sensory and nonsensory cells, the actual molecular components involved may be unique. Other reviews on molecular chemosensory mechanisms have appeared recently (Getchell et al. 1984; Lancet 1986, 1988a,b; Anholt 1987; Lancet and Pace 1987; Pace and Lancet 1987; Snyder et al. 1988). Other theories of olfaction have been described (Davies 1971).
A survey of commercially available manipulators, end-effectors, and delivery systems for reactor decommissioning activities (1996)

Numerous nuclear facilities owned by the U.S. Department of Energy (DOE) are under consideration for decommissioning. Currently, there are no standardized, automated, remote systems designed to dismantle and thereby reduce the size of activated reactor components and vessels so that they can be packaged and shipped to disposal sites. Existing dismantling systems usually consist of customized, facility-specific tooling that has been developed to dismantle a specific reactor system. Such systems have a number of drawbacks. Generally, current systems cannot be disassembled, moved, and reused. Developing and deploying the tooling for current systems is expensive and time-consuming. In addition, the amount of manual work is significant because long-handled tools must be used; as a result, personnel are exposed to excessive radiation. A standardized, automated, remote system is therefore needed to deliver the tooling necessary to dismantle nuclear facilities at different locations. Because this system would be reusable, it would produce less waste. The system would also save money because of its universal design, and it would be more reliable than current systems.
Metabolic impact of glucagon deficiency (2011)

Multiple bioactive peptides are produced from proglucagon encoded by glucagon gene (Gcg). Glucagon is produced in islet α-cells through processing by prohormone convertase 2 (Pcsk2) and exerts its action through the glucagon receptor (Gcgr). Although it is difficult to produce a genetic model that harbours isolated glucagon deficiency without affecting the production of other peptides derived from proglucagon, three different animal models that harbour deficiencies in glucagon signalling have been generated by gene targeting strategy. Although both Pcsk2(-/-) and Gcgr(-/-) mice display lower blood glucose levels, homozygous glucagon-GFP knock-in mice (Gcg(gfp/gfp) ) display normoglycaemia despite complete glucagon deficiency. In Gcg(gfp/gfp) mice, the metabolic impact of glucagon deficiency is probably ameliorated by lower plasma insulin levels and glucagon-independent mechanisms that maintain gluconeogenesis. As both Pcsk2(-/-) and Gcgr(-/-) mice exhibit increased production of glucagon-like peptide-1 (GLP-1), which is absent in Gcg(gfp/gfp), GLP-1 is the likely cause of the difference in metabolic impact of glucagon deficiency in these animal models. Although all the three models display islet 'α'-cell hyperplasia, the mechanisms involved remain to be elucidated. Studies using Pcsk2(-/-), Gcgr(-/-) and Gcg(gfp/gfp) mice, especially in combination with α-cell ablation models such as pancreas-specific aristaless-related homeobox (ARX) knockout mice, should further clarify the physiological and pathological roles of glucagon in the regulation of metabolism and the control of islet cell differentiation and proliferation.
Imparting Directional Dependence on Log-derived Permeability (2001)

Cost effective, efficient production of hydrocarbons depends on accurate reserves estimates, reservoir architecture, and hydrocarbon distribution. In addition, a complete reservoir description including both horizontal and vertical permeability is critical to efficient development strategy. Hydrocarbon recovery efficiency depends on many factors, but one key parameter is the ratio of vertical to horizontal permeability.There are numerous ways to estimate permeability. It is now possible to estimate permeability from continuous formation evaluation measurements. However, it remains difficult to determine directional permeability. NMR logs are used routinely to estimate permeability, but NMR-derived permeability is based on scalar properties (e.g., ϕ, T2 distributions from NMR, bulk volume irreducible water) and is inherently a scalar property.Few formation evaluation measurements provide directional information. Dip and image logs provide bed thickness and layer dip information. However, only the new multi-component induction instrument (3DEXSM) and crossed-dipole shear-wave acoustic tools provide direct measurements of macroscopic formation anisotropy.In this paper, we explore theoretically and with real data the computation of permeability anisotropy. We use laminated sand models as well as macroscopic models based on the resistivity anisotropy measurements to estimate kv:kh ratios. In addition to multi-component induction data, we explore standalone and joint interpretation of NMR property variations to predict the macroscopic reservoir permeability anisotropy.
Nitrogen and Sulfur Codoped Graphite Foam as a Self‐Supported Metal‐Free Electrocatalytic Electrode for Water Oxidation (2015)

The oxidation of water to produce oxygen gas is related to a variety of energy storage systems. Thus, the development of efficient, cheap, durable, and scalable electrocatalysts for oxygen evolution reaction (OER) is of great importance. Here, a high‐performance OER catalyst, nitrogen and sulfur codoped graphite foam (NSGF) is reported. This NSGF is prepared from commercial graphite foil and directly applied as an electrocatalytic electrode without using a current collector and a polymeric binder. It exhibits an extremely low overpotential of 0.380 V to reach a current density of 10 mA cm −2 and shows fast kinetics with a small Tafel slope of 96 mV dec −1 in 0.1 m KOH. This electrocatalytic performance is superior or comparable to those of previously reported metal‐free OER catalysts.
Early detection of acute transmural myocardial ischemia by the phasic systolic-diastolic changes of local tissue electrical impedance (2015)

Myocardial electrical impedance is influenced by the mechanical activity of the heart. Therefore, the ischemia-induced mechanical dysfunction may cause specific changes in the systolic-diastolic pattern of myocardial impedance, but this is not known. This study aimed to analyze the phasic changes of myocardial resistivity in normal and ischemic conditions. Myocardial resistivity was measured continuously during the cardiac cycle using 26 different simultaneous excitation frequencies (1 kHz-1 MHz) in 7 anesthetized open-chest pigs. Animals were submitted to 30 min regional ischemia by acute left anterior descending coronary artery occlusion. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow were recorded simultaneously. Baseline myocardial resistivity depicted a phasic pattern during the cardiac cycle with higher values at the preejection period (4.19 ± 1.09% increase above the mean, P < 0.001) and lower values during relaxation phase (5.01 ± 0.85% below the mean, P < 0.001). Acute coronary occlusion induced two effects on the phasic resistivity curve: 1) a prompt (5 min ischemia) holosystolic resistivity rise leading to a bell-shaped waveform and to a reduction of the area under the LV pressure-impedance curve (1,427 ± 335 vs. 757 ± 266 Ω·cm·mmHg, P < 0.01, 41 kHz) and 2) a subsequent (5-10 min ischemia) progressive mean resistivity rise (325 ± 23 vs. 438 ± 37 Ω·cm at 30 min, P < 0.01, 1 kHz). The structural and mechanical myocardial dysfunction induced by acute coronary occlusion can be recognized by specific changes in the systolic-diastolic myocardial resistivity curve. Therefore these changes may become a new indicator (surrogate) of evolving acute myocardial ischemia.
Optical intensity modulation to 40 GHz using a waveguide electro-optic switch (1987)

We report the intensity modulation of an optical carrier at frequencies as high as 40 GHz using a Ti:LiNbO3 optical waveguide switch. The device is shown to exhibit a small-signal electrical 3 dB bandwidth of &gt;22 GHz and −8 dB response at 40 GHz. A high-speed self-electro-optic-sampling arrangement based on a mode-locked injection laser is used to observe the modulation in the time domain.
Induction by cyclophosphamide administration of two distinct anti-tumor effector cells at tumor site and spleen of mice transplanted with MOPC-104E plasmacytoma. (1989)

BALB/c mice were inoculated intraperitoneally (i.p.) with MOPC-104E syngeneic plasmacytoma cells and seven days later the mice were treated with i.p. cyclophosphamide (CY). All mice exhibited a complete regression of MOPC-104E, and in addition acquired the resistance to second challenge of MOPC-104E, but not to syngeneic Meth-A fibrosarcoma. Following CY treatment, a large number of viable MOPC-104E cells were seen in the peritoneal cavity of the mice on day 7, and then they decreased and disappeared on day 14. By contrast, athymic BALB/c nude mice with MOPC-104E did not respond to CY and died. Only a transient decrease in the number of tumor cells was observed in the peritoneal cavity of nude mice. Following CY treatment, whole peritoneal cells (tumor cells and peritoneal exudate cells) was not transplanted to conventional mice, while transplantation was possible following treatment of whole peritoneal cells with anti-Thy1, anti-Lyt 1 or anti-Lyt 2 plus complement (C). The in vivo anti-tumor activity of spleen cells of mice in regression was nullified by treatment with anti-Thy 1 and anti-Lyt 1 plus C, but not anti-Lyt 2 plus C. These results indicate that CY administration results in only a transient decrease of tumor cell number and that an induction of Lyt 1 +, Lyt 2 + T cells in the peritoneal cavity and Lyt 1 + T cells in spleen may be responsible for a complete disappearance of tumor cells.
Influence of Grown-in Hydrogen on Thermal Donor Formation and Oxygen Precipitation in Czochralski Silicon Crystals (1994)

Using hydrogen-enhanced thermal donor formation and hydrogen-enhanced oxygen precipitate nuclei formation, we confirmed the presence of hydrogen in as-grown Czochralski (CZ) silicon (Si) ingots. Hydrogen concentrations in as-grown ingots were very low at 2.5×10 11 cm -3 . We found that even such a small amount of hydrogen influences the quality of as-grown CZ Si crystals due to hydrogen-enhanced oxygen precipitate nuclei formation caused by in situ annealing during crystal growth. Reducing hydrogen contamination during crystal growth is important in obtaining high-quality CZ Si crystals.
The Thermodynamic Behavior of the Si‐H System and Its Role in Si‐CVD from SiH4 (1992)

Thermodynamic calculations of the Si‐H system were performed at typical chemical vapor deposition conditions of total pressure, partial pressure of , ambient, and temperature. Effects of the conditions on the equilibria of the system were examined, and homogeneous reaction mechanisms in the system were qualitatively discussed. The main conclusions include that Si deposition at low temperatures is due to alone and high‐temperature film deposition is dominated by gaseous silane intermediates produced through homogeneous reactions of . As the homogeneous reactions develop, homogeneous nucleation of occurs. Both inert ambient and low pressure promote the homogeneous reactions.
Sensor assisted wireless communication (2010)

The nature of human mobility demands that mobile devices become agile to diverse operating environments. Coping with such diversity requires the device to assess its environment, and trigger appropriate responses to each of them. While existing communication subsystems rely on in-band wireless signals for context-assessment and response, we explore a lateral approach of using out-of-band sensor information. We propose a relatively novel framework that synthesizes in-band and out-of-band information, facilitating more informed communication decisions. We believe that further research in this direction could enable a new kind of device agility, deficient in today's communication systems. Since such a framework is located at the boundaries of mobile sensing and wireless communication, we call it sensor assisted wireless communication.