gebhart/patrepeval huggingface dataset:
DDIS-20. IMIPRIDONE STRUCTURE ACTIVITY RELATIONSHIP UNCOVERS ONC206 AS THE NEXT BITOPIC DRD2 ANTAGONIST FOR ONCOLOGY WITH DIFFERENTIATED RECEPTOR PHARMACOLOGY (2019)

Abstract ONC201 is the first bitopic antagonist of dopamine receptor D2 (DRD2) in oncology clinical trials, which have shown that the small molecule is well tolerated and induces durable tumor regressions in H3 K27M-mutant glioma patients. ONC201 possesses a unique tri-heterocyclic core structure that prompted a medicinal chemistry exploration following its successful clinical translation. Chemical derivatization of the ONC201 pharmacophore from an angular to a linear isomer ablated DRD2 antagonist activity and anti-cancer activity, indicating the core structure integrity is critical. A series of analogs that share the same core structure, called imipridones, were profiled for modulation of β-arrestin recruitment to GPCRs and anti-cancer efficacy. The profiled imipridones exhibited a heterogeneous spectrum of GPCR agonist/antagonist activity that was exclusive to Class A GPCRs. The addition of electron withdrawing groups to one of two peripheral benzyl rings enhanced the potency of GPCR engagement and anti-cancer effects, while derivatization of the other benzyl ring was inactivating. Among the GPCR hits identified, maximal variance in imipridone GPCR antagonism was identified for DRD2/DRD3. ONC206 emerged as the most selective and potent antagonist for DRD2/DRD3 with a Ki of ~320nM for DRD2 with complete specificity across human GPCRs and complete DRD2 antagonism. Schild analyses of ONC206 in cAMP and β-Arrestin recruitment assays revealed hallmarks of non-competitive DRD2 antagonism, unlike antipsychotics but similar to ONC201. Shotgun mutagenesis across DRD2 identified 7 residues critical for ONC206-mediated antagonism at orthosteric and allosteric sites. Six residues were critical for ONC201 and ONC206, however the impact varied between the two compounds and one allosteric residue was exclusive to ONC206. Structural mapping revealed that some ONC206-critical allosteric residue interactions are located at the interface of TM-IV and –V that mediates the DRD2 homodimer interface. Thus, ONC206 is a bitopic DRD2 antagonist that may be poised to address oncogenic DRD2 monomers or dimers.
Adaptive LDPC-coded polarization multiplexed coherent optical OFDM in optically-routed networks (2009)

We present a power-variable rate-adaptive LDPC-coded polarization multiplexed coherent OFDM scheme, suitable for use in optically-routed networks in which different lightwave paths experience different penalties due to deployment of ROADMs and WXCs. We demonstrate that channel capacity can be closely approached with proposed scheme.
Noble Gas Immobilization in Zeolites (1982)

Abstract It was discovered that the noble gases Ar, Kr and Xe can be trapped firmly in type A zeolites as well as in mordenites and chabazites when the molecular sieves are hydrothermally vitrified at temperatures between 340 and 650°C in the presence of pressurized gas. The occurrence of trapping in an amorphous nonzeolitic species was demonstrated by X‐ray diffraction, neutron scattering and electron scattering. The change in structure of loaded zeolites is also manifested by a substantial loss in sorption capacity for water as well as an almost complete disappearance of the specific surface area. – The gas release rates at temperatures below 550°C were found to be extremely low. The activation energies for the diffusion of Kr through amorphous Ca and Mg exchanged 5 A zeolite were determined to be 209 ± 15 and 187 ± 16 kJ/mol respectively. The estimated diffusion coefficients are exceedingly small. The trapped gas is neither liberated by hot water nor by liq. Rb at 150°C.
Characteristic Study of Vector-controlled Direct-driven Permanent Magnet Synchronous Generator in Wind Power Generation (2009)

Abstract With the advance of power electronics, direct-driven permanent magnet synchronous generators have drawn increased interest to wind turbine manufacturers due to its advantages over other variable-speed wind turbines. This article studies permanent magnet synchronous generator characteristics under the general d-q control strategy in the rotor-flux-oriented frame so as to benefit the development of advanced permanent magnet synchronous generator control technology. Compared to traditional approaches, the specific features of the article are (1) a steady-state permanent magnet synchronous generator model in a d-q reference frame, (2) a simulation mechanism that reflects the general permanent magnet synchronous generator d-q control strategy, (3) an integrative study that combines generator-converted power with extracted wind power characteristics, and (4) a joint investigation incorporating both steady-state and transient evaluations. Extensive simulation-based analysis is conducted to study how permanent magnet synchronous generator characteristics are affected by different d-q control conditions and are interacted with wind power drive characteristics in power generation and speed regulation of a permanent magnet synchronous generator wind turbine.
Localization of a Substrate Specificity Domain in the Multidrug Resistance Protein (1999)

Multidrug resistance protein (MRP) confers resistance to a number of natural product chemotherapeutic agents. It is also a high affinity transporter of some physiological conjugated organic anions such as cysteinyl leukotriene C(4) and the cholestatic estrogen, 17beta-estradiol 17(beta-D-glucuronide) (E(2)17betaG). We have shown that the murine orthologue of MRP (mrp), unlike the human protein, does not confer resistance to common anthracyclines and is a relatively poor transporter of E(2)17betaG. We have taken advantage of these functional differences to identify region(s) of MRP involved in mediating anthracycline resistance and E(2)17betaG transport by generating mrp/MRP hybrid proteins. All hybrid proteins conferred resistance to the Vinca alkaloid, vincristine, when transfected into human embryonic kidney cells. However, only those in which the COOH-terminal third of mrp had been replaced with the corresponding region of MRP-conferred resistance to the anthracyclines, doxorubicin, and epirubicin. Exchange of smaller segments of the COOH-terminal third of the mouse protein by replacement of either amino acids 959-1187 or 1188-1531 with those of MRP produced proteins capable of conferring some level of resistance to the anthracyclines tested. All hybrid proteins transported cysteinyl leukotriene C(4) with similar efficiencies. In contrast, only those containing the COOH-terminal third of MRP transported E(2)17betaG with an efficiency comparable with that of the intact human protein. The results demonstrate that differences in primary structure of the highly conserved COOH-terminal third of mrp and MRP are important determinants of the inability of the murine protein to confer anthracycline resistance and its relatively poor ability to transport E(2)17betaG.
Addressing Nonlinear Relative Motion For Spacecraft Collision Probability (2006)

Linear methods for computing satellite collision probability can be extended to accommodate nonlinear relative motion in the presence of changing position and velocity uncertainties. Collision probability analysis for spherical objects exhibiting linear relative motion is accomplished by combining covariances and physical object dimensions at the point of closest approach. The resulting covariance ellipsoid and hardbody are projected onto the plane perpendicular to relative velocity by assuming linear relative motion and constant positional uncertainty throughout the brief encounter. Collision potential is determined from the object footprint on the projected, two-dimensional, covariance ellipse. For nonlinear motion, the dimension associated with relative velocity must be reintroduced. This can be simply done by breaking the collision tube into sufficiently small cylinders such that the sectional motion is nearly linear, computing the linear probability associated with each section, and then summing. The method begins with object position and velocity data at the time of closest approach. Propagation of position, velocity, and covariance is done forward/backward in time until a user limit is reached. An alternate method is presented that creates a voxel grid in Mahalanobis space, computes the probability of each affected voxel as the combined object passes through the space, and sums. These general methods are not dependent on a specific propagator or linear probability model.
<title>Clinical review of pulsed ruby laser depilation</title> (1999)

This paper is intended to outline the current thinking regarding the process involved in depilation by pulsed ruby laser. The key laser parameters of wavelength, pulse duration, energy density, spot size and spatial profile will be discussed together with their impact on the outcome of the procedure. A parallel series of clinical trials have been carried out in a number of centers on both medical complications of hair growth and the cosmetic use of the technology. The results of these trials detail the efficacy of the treatment as well as the incidence of side-effects or complications.
Computer-aided surface reconstruction of interference contours (1982)

A computer-aided system for reconstruction of the surface of an object from optically generated interferometric fringes is described conceptually, and the parts of the system are demonstrated. Fringe patterns of macroscopic objects were produced with moire contouring, while a reflection interference microscope was used to examine minute surface features. Three-dimensional shaded images of the surface were generated using techniques of image processing and computer graphics. An algorithm for obtaining wire frame surface representations from TV images of fringes is described, and the limitations of the proposed system are discussed.
Epidemiological features of BLV infection in Japan from 2012 to 2013 (2015)

Bovine leukemia virus (BLV) is causative virus of enzootic bovine leukosis (EBL) that is malignant B lymphoma. BLV infected cattle to be asymptomatic carrier, persistent lymphocytosis (PL), and bovine leukosis. BLV is spreading over the world and causes serious problems. After infection, BLV genome integrated and can be amplified during latency periods. We designed degenerated primers by Coordination of Common Motifs (CoCoMo) algorism to establish a new quantitative real-time PCR method (BLV-CoCoMo-qPCR) that measure the proviral load of known and novel BLV variants. In present study, to analyze correlation between proviral load and risk factors such as breeds, numbers of lymphocytes, age and reproductive history, we collected blood and serum from 1,010 cattle in 44 BLV positive farms of the 22 prefectures in Japan, and measured BLV proviral load and detected anti-BLV antibody. The 682 of 1,010 samples (67.5%) were positive by BLV-CoCoMo-qPCR and ELISA, 22 of 1,010 samples (2.2%) were positive by only BLV-CoCoMo-qPCR, and 13 of 1,010 samples (1.3%) were positive by only ELISA. We detected BLV provirus from 22 samples that showed BLV negative by serological test, and average of proviral load was 31,533 copies. Therefore, BLV-CoCoMo-qPCR seems useful methods to determine BLV infection. It was not correlation between age and proviral load. Meanwhile, positive correlation showed between lymphocytes and proviral load. Therefore, we classified BLV provirus positive samples in three groups by disease progression of lymphocytosis (asymptomatic carrier, false positive and lymphocytosis) by age and numbers of lymphocytes, and compared proviral load between these groups. In fact, proviral load were increased according disease progression of lymphocytosis. Thus, the measurement of proviral load seems to be available for pathologic diagnosis of lymphocytosis.
ChemInform Abstract: THE 6‐ AND 7‐ARYL‐1,2,4‐TRIAZOLO(4,3‐B)(1,2,4)TRIAZINES. SYNTHESIS AND CHARACTERIZATION (1980)

Abstract Phenylglyoxalmonoxim (I) reagiert mit dem Diamino‐triazol (II) bei längerem Erhitzen unter Umlagerung zu einem Triazolotriazin (III), das unabhängig aus dem Hydrazin (IV) hergestellt werden kann.
Predicting bilirubin neurotoxicity in jaundiced newborns (2010)

Overcoming these misconceptions and integrating Bf and BT into the management of neonatal jaundice may help move clinical practice from its tradition-based approach centered primarily on BT toward an evidence-based approach that will substantially improve our ability to predict bilirubin neurotoxicity and improve the clinical management of this generally benign, but potentially catastrophic, newborn condition.
Proxy cache coherency and replacement-towards a more complete picture (2003)

This work studies the interaction of Web proxy cache coherency and replacement policies using trace-driven simulations. We specifically examine the relative importance of each type of policy in affecting the overall costs, the potential of incorporating coherency issues in cache replacement and the inclusion of additional factors such as frequency of resource use in replacement and coherency policies. The results show that the cache replacement policy in use is the primary cost determinant for relatively small caches, while the cache coherency policy is the determinant for larger caches. Incorporating cache coherency issues in cache replacement policies yields little improvement in overall performance. The use of access frequency in cache replacement, along with temporal locality and size information, results in a simple and better performing policy than found in previously published work. Combining this new replacement policy with the best piggyback-based cache coherency policy results in a 4.5% decrease in costs and 89% reduction in staleness ratio when compared to policy combinations in current use. Preliminary work indicates that cache replacement and coherency policies continue to affect costs in the presence of HTTP protocol enhancements such as persistent connections.
A general synthesis of 2′‐deoxy‐2′‐[<sup>18</sup>F]fluoro‐1‐<i>β</i>‐D‐arabinofuranosyluracil and its 5‐substituted nucleosides (2003)

Abstract Several 2′‐deoxy‐2′‐[ 18 F]fluoro‐1‐ β ‐D‐arabinofuranosyluracil derivatives have been synthesized. Coupling of 1‐bromo‐2‐deoxy‐2‐[ 18 F]fluoro‐3,5‐di‐O‐benzoyl‐ α ‐D‐arabinofuranose 2 with protected uracil derivatives 3a–e followed by hydrolysis and high‐performance liquid chromatography purification produced the radiolabeled nucleosides 4a–e in 15–30% yield (d. c.), >99% radiochemical purity and 55.5–103.6 GBq/µmol specific activities. Copyright © 2003 John Wiley & Sons, Ltd.
Rapid Three-Dimensional Printing in Water Using Semiconductor–Metal Hybrid Nanoparticles as Photoinitiators (2017)

Additive manufacturing processes enable fabrication of complex and functional three-dimensional (3D) objects ranging from engine parts to artificial organs. Photopolymerization, which is the most versatile technology enabling such processes through 3D printing, utilizes photoinitiators that break into radicals upon light absorption. We report on a new family of photoinitiators for 3D printing based on hybrid semiconductor-metal nanoparticles. Unlike conventional photoinitiators that are consumed upon irradiation, these particles form radicals through a photocatalytic process. Light absorption by the semiconductor nanorod is followed by charge separation and electron transfer to the metal tip, enabling redox reactions to form radicals in aerobic conditions. In particular, we demonstrate their use in 3D printing in water, where they simultaneously form hydroxyl radicals for the polymerization and consume dissolved oxygen that is a known inhibitor. We also demonstrate their potential for two-photon polymerization due to their giant two-photon absorption cross section.
Ordinal UNLOC: Target Localization With Noisy and Incomplete Distance Measures (2021)

A main challenge in target localization arises from the lack of reliable distance measures. This issue is especially pronounced in indoor settings due to the presence of walls, floors, furniture, and other dynamically changing conditions, such as the movement of people and goods, varying temperature and air flows. Here, we develop a new computational framework to estimate the location of a target without the need for reliable distance measures. The method, which we term Ordinal UNLOC, uses only ordinal data obtained from comparing the signal strength from anchor pairs at known locations to the target. Our estimation technique utilizes rank aggregation, function learning as well as proximity-based unfolding optimization. As a result, it yields accurate target localization for common transmission models with unknown parameters and noisy observations that are reminiscent of practical settings. Our results are validated by both numerical simulations and hardware experiments.
miR-409-3p/-5p Promotes Tumorigenesis, Epithelial-to-Mesenchymal Transition, and Bone Metastasis of Human Prostate Cancer (2014)

miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding bears particular translational importance as miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bone metastatic prostate cancer.
Binarization of Gray-Scaled Digital Images Via Fuzzy Reasoning (2002)

A new fast-computational technique based on fuzzy entropy measure has been developed to find an optimal binary image threshold. In this method, the image pixel membership functions are dependent on the threshold value and reflect the distribution of pixel values in two classes; thus, this technique minimizes the classification error. This new method is compared with two of the best-known threshold selection techniques, Otsu and Huang-Wang. The performance of the proposed method supersedes the performance of Huang- Wang and Otsu methods when the image consists of textured background and poor printing quality. The three methods perform well but yield different binarization approaches if the background and foreground of the image have well-separated gray-level ranges.
Remote Sensing of Atmospheric Methane with Simultaneous Ranging Using Chirped Laser Dispersion Spectroscopy (2016)

We present a new sensing technology that allows for simultaneous sensing and ranging using chirped laser dispersion spectroscopy (CLaDS). In conjunction with previous works demonstrating the effectiveness of CLaDS for remote sensing, this new configuration yields spectroscopic and ranging information from a single measurement, and is implemented for continuous, multi-path detection of atmospheric methane.
Cell-Seeding Techniques in Vascular Tissue Engineering (2010)

Previous studies have demonstrated the benefits of cell seeding in the construction of tissue-engineered vascular grafts (TEVG). However, seeding methods are diverse and no method is clearly superior in either promoting seeding efficiency or improving long-term graft function. As we head into an era during which a variety of different TEVG are under investigation in clinical trials around the world, it is important to consider the regulatory issues surrounding the translation of these technologies. In this review, we summarize important advances in the field of vascular tissue engineering, with particular attention on cell-seeding techniques for TEVG development and special emphasis placed on regulatory issues concerning the clinical translation of these various methods.
A Camera Calibration Method using Concentric Circles for Vision Applications (2002)

In this paper, we present a new method for camera calibration using concentric circles. We demonstrate that camera calibration is possible using two views of a concentric circle with known size. A new method to determine the position of the projected center of the circle is introduced. Based on the accurate estimation of the projected circle center of two sets of 3-D concentric circles, the proposed calibration method estimates the intrinsic camera parameters using two sets of 3-D concentric circles obtained from the same viewpoint. We validate the performance of the method using both synthetic and real images. Our method shows a comparable performance with respect to similar calibration methods using a plane. The use of concentric circles, however, greatly simplifies the calibration problem. We also demonstrate the feasibility of the proposed calibration method through the recovery of 3-D structure of an object, placed on a turntable, using a sequence of images taken from the static cameras.
Development of GABA<sub>A</sub> Receptor Subtype-Selective Imidazobenzodiazepines as Novel Asthma Treatments (2016)

Recent studies have demonstrated that subtype-selective GABAA receptor modulators are able to relax precontracted human airway smooth muscle ex vivo and reduce airway hyper-responsiveness in mice upon aerosol administration. Our goal in this study was to investigate systemic administration of subtype-selective GABAA receptor modulators to alleviate bronchoconstriction in a mouse model of asthma. Expression of GABAA receptor subunits was identified in mouse lungs, and the effects of α4-subunit-selective GABAAR modulators, XHE-III-74EE and its metabolite XHE-III-74A, were investigated in a murine model of asthma (ovalbumin sensitized and challenged BALB/c mice). We observed that chronic treatment with XHE-III-74EE significantly reduced airway hyper-responsiveness. In addition, acute treatment with XHE-III-74A but not XHE-III-74EE decreased airway eosinophilia. Immune suppressive activity was also shown in activated human T-cells with a reduction in IL-2 expression and intracellular calcium concentrations [Ca2+]i in the presence of GABA or XHE-III-74A, whereas XHE-III-74EE showed only partial reduction of [Ca2+]i and no inhibition of IL-2 secretion. However, both compounds significantly relaxed precontracted tracheal rings ex vivo. Overall, we conclude that the systemic delivery of a α4-subunit-selective GABAAR modulator shows good potential for a novel asthma therapy; however, the pharmacokinetic properties of this class of drug candidates have to be improved to enable better beneficial systemic pharmacodynamic effects.
Simultaneous, single-detector fluorescence detection of multiple fluorescent dyes (2010)

Microfluidics has made great progress in integrating many aspects of biological analysis and testing into the microscale. One aspect which has proven challenging to miniaturize has been fluorescence testing, as a complete fluorescence system requires an integrated light source, detector and filters to filter out the excitation light (from the light source) from the detector. Here we demonstrate that with polarization filtering of the excitation light and multiple dye sources modulated at different frequencies, a high-sensitivity, multi-dye system with one detector can be realized. Simultaneous detection and quantition of a mixture of two different dyes is demonstrated with no physical change in the measurement setup. The degree of interaction of the dyes is measured. This system is readily adaptable to integrated lab-on-a-chip microfluorescence.
Electrospinning of fluorescent fibers from CdSe/ZnS quantum dots in cellulose triacetate (2010)

Abstract Fluorescent cellulose triacetate (CTA) fibers were prepared by electrospinning solutions of CTA dissolved in an 8 : 2 v/v cosolvent system of methylene chloride (MC) and methanol (MeOH) which contained CdSe/ZnS quantum dots (QDs). The relatively low loading of colloidal nanoparticles was sufficient to impart fluorescence to the fibers but did not significantly alter fiber morphologies, which tended toward smooth surfaces with the occasional longitudinal feature. The fibers were birefringent due to the alignment of the polymer chains which occurred during electrospinning and had widths on the order of a hundred nanometers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011