gebhart/patrepeval huggingface dataset:
MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition (2015)

CDK4 inhibitors (CDK4i) earned Breakthrough Therapy Designation from the FDA last year and are entering phase III clinical trials in several cancers. However, not all tumors respond favorably to these drugs. CDK4 activity is critical for progression through G1 phase and into the mitotic cell cycle. Inhibiting this kinase induces Rb-positive cells to exit the cell cycle into either a quiescent or senescent state. In this report, using well-differentiated and dedifferentiated liposarcoma (WD/DDLS) cell lines, we show that the proteolytic turnover of MDM2 is required for CDK4i-induced senescence. Failure to reduce MDM2 does not prevent CDK4i-induced withdrawal from the cell cycle but the cells remain in a reversible quiescent state. Reducing MDM2 in these cells drives them into the more stable senescent state. CDK4i-induced senescence associated with loss of MDM2 is also observed in some breast cancer, lung cancer and glioma cell lines indicating that this is not limited to WD/DDLS cells in which MDM2 is overexpressed or in cells that contain wild type p53. MDM2 turnover depends on its E3 ligase activity and expression of ATRX. Interestingly, in seven patients the changes in MDM2 expression were correlated with outcome. These insights identify MDM2 and ATRX as new regulators controlling geroconversion, the process by which quiescent cells become senescent, and this insight may be exploited to improve the activity of CDK4i in cancer therapy.
Thermotropic chiral nematic side-chain polymers and cyclic oligomers (1996)

For all the theoretical, experimental and computational research on chiral nematic systems over the last four decades, understanding of cholesteric mesomorphism from the molecular perspective is still rather limited at the present time. Nevertheless, the unique property of selective wavelength reflection accompanied by circular polarization has presented tremendous potential for various optical applications. Theories governing optical birefringence and selective reflection bandwidth are outlined to serve as a foundation for molecular design. Both polymeric and low molar mass glass-forming chiral nematics are surveyed in terms of chemical structure, thermotropic and optical properties. Characterized by relative ease of processing, the low molar mass approach is illustrated with our recent results in terms of design concept, materials synthesis and characterization. We also highlight outstanding issues that need to be addressed to help advance chiral nematics as a class of advanced optical materials.
Surface segmentation based on the luminance and color statistics of natural scenes (2003)

The luminance and color of surfaces in natural scenes are relatively independent under certain linear transformations, with the luminance of a surface providing little information about the color of that surface, and vice versa. However, differences in luminance between two locations in a natural scene remain strongly associated with differences in color. We used the statistics of the spatiochromatic structure of natural scenes as the priors for a Bayesian model that decides whether or not two points within an image fall on the same surface. This model provides a biologically plausible algorithm for surface segmentation that models observer segmentations well.
Cation- and Peptide-Binding Properties of Human Calmodulin-like Skin Protein (2002)

Human CLSP, a new Ca(2+)-binding protein specifically expressed in differentiated keratinocytes, is a 15.9 kDa, four EF-hand containing protein with 52% sequence identity to calmodulin (CaM). The protein binds four Ca(2+) ions at two pairs of sites with [Ca(2+)](0.5) values of 1.2 and 150 microM, respectively. Mg(2+) at millimolar concentrations strongly decreases the affinity for Ca(2+) of the two high-affinity sites, but has no effect on the low-affinity sites. The protein can also bind two Mg(2+) ([Mg(2+)](0.5) = 57 microM) at the sites of high Ca(2+) affinity. Thus, as fast skeletal muscle troponin C (TnC), CLSP possesses two high-affinity Ca(2+)-Mg(2+) mixed sites and two low-affinity Ca(2+)-specific sites. Studies on the isolated recombinant N- (N-CLSP) and C-terminal half domains of CLSP (C-CLSP) revealed that, in contrast to the case of TNC, the high-affinity Ca(2+)-Mg(2+) mixed sites reside in the N-terminal half. The binding of cations modifies the intrinsic fluorescence of the two Tyr residues. Upon Ca(2+) binding, hydrophobicity is exposed at the protein surface that can be monitored with a fluorescent probe. The Ca(2+)-dependency of the two conformational changes is biphasic in the absence of Mg(2+), but monophasic in the presence of 2 mM Mg(2+), both corresponding closely to direct binding of Ca(2+) to CLSP. In the presence of Ca(2+), human CLSP forms a high-affinity 1:1 complex with melittin, a natural peptide considered to be a model for the interaction of CaM with its targets. In the complex, CLSP binds Ca(2+) with high affinity to all four binding sites. Isolated N- and C-CLSP show only a weak interaction with melittin, which is enhanced when both halves are simultaneously presented to the model peptide.
Color Correcting JPEG Compressed Images (1997)

Many high end printing systems store and/or transmit compressed images to save bandwidth, memory, and disk space. Prior to printing, the system will decompress and then color correct the image to compensate for the characteristics of a particular printer. In the conventional architecture, the decompression step converts the image from some encoded format (e.g. JPEG with Huffman encoding) into the spatial domain. In this domain, the color image may be stored in some standard device independent color space such as IJG/CCIR YCrCb, SMPTE RGB or Kodak Photo Ycc. The ensuing color correction transforms colors from this space to device coordinates. Our proposed technique uses information about the JPEG compressed format to gain efficiency in the color transformation.
Heparosan-glucuronate 5-epimerase: Molecular cloning and characterization of a novel enzyme (2015)

Iduronic acid (IdoA) is a critical component of heparan sulfate in its interaction with functional proteins. Heparosan-N-sulfate-glucuronate 5-epimerase (HNSG-5epi) converts d-glucuronic acid (GlcA) residues in N-sulfated heparosan (NS-heparosan), as an intermediate in heparan sulfate biosynthesis, to IdoA. In the present study, the authors discovered a different 5-epimerase, designated HG-5epi (heparosan-glucuronate 5-epimerase), that is involved in acharan sulfate biosynthesis and possesses novel substrate specificity. A candidate cDNA of HG-5epi was cloned from the cDNA library of Achatina fulica. The cloned cDNA contained a whole coding region that predicts a type II transmembrane protein composed of 601 amino acid residues. The amino acid sequence of HG-5epi is homologous to that of HNSG-5epi. Recombinant HG-5epi was expressed in insect cells and its enzymatic properties characterized. As expected, HG-5epi epimerizes GlcA residues in heparosan, but not in NS-heparosan. Conversion of IdoA to GlcA was also catalyzed by HG-5epi when completely desulfated N-acetylated heparin was used as the substrate, indicating a reversible reaction mechanism. At equilibrium of the epimerization, the proportion of IdoA in the reaction product reached up to 30% of total hexuronic acid. To our knowledge, this is the first report to describe an enzyme that catalyzes the epimerization of non-sulfated heparosan. This new enzyme may be applied to the study of synthetic heparan sulfate-related polysaccharides having certain biological and pharmacological activities. In addition, a new method using anion-exchange HPLC connected to a post-column fluorescent labeling system was developed for analyzing hexuronic acid isomers.
Use Of Green Porphyrinsto Treat Neovasculature In The Eyes (1998)

Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions.
Avoiding Divergence in Multi-Area State Estimation (2019)

This paper is concerned about the divergence of state estimation solution for multi-area power grids. Such cases typically occur due to a single anomaly in the measurement set or network model, yet will cause failure of the state estimator to provide the solution for the entire system. The objective of our study is to develop an approach that will allow detection, identification, and isolation of the anomaly during the state estimation solution so that a large percentage of the system states can still be estimated, while isolating the anomaly that is causing the divergence of the estimator. The proposed approach is described in detail and its effective utilization for a very large utility system is illustrated by simulations.
Context-Dependent Multiple Distribution Phonetic Modeling with MLPs (1992)

A number of hybrid multilayer perceptron (MLP)/hidden Markov model (HMM) speech recognition systems have been developed in recent years (Morgan and Bourlard, 1990). In this paper, we present a new MLP architecture and training algorithm which allows the modeling of context-dependent phonetic classes in a hybrid MLP/HMM framework. The new training procedure smooths MLPs trained at different degrees of context dependence in order to obtain a robust estimate of the context-dependent probabilities. Tests with the DARPA Resource Management database have shown substantial advantages of the context-dependent MLPs over earlier context-independent MLPs, and have shown substantial advantages of this hybrid approach over a pure HMM approach.
Numerical and experimental evaluations of multilayer mirror for soft x-rays (1989)

For the wavelength region from 24A to 44A, selection of materials used for the multi-layer mirror was done by computer simulation. The multilayers of Si02/Ni were produced by the ion beam sputtering method and evaluated by the C-K line, experimentally. In order to analyze scattering in the region of 0 ~ λ comparisons between the experimental results, and the solutions of Beckmann's theory and Extinction theory were done.
Local contrast enhancement (2007)

We introduce a novel algorithm for local contrast enhancement. The algorithm exploits a background image which is estimated with an edge-preserving filter. The background image controls a gain which enhances important details hidden in underexposed regions of the input image. Our designs for the gain, edge-preserving filter and chrominance recovery avoid artifacts and ensure the superior image quality of our results, as extensively validated by user evaluations. Unlike previous local contrast methods, ours is fully automatic in the sense that it can be directly applied to any input image with no parameter adjustment. This is because we exploit a trainable decision mechanism which classifies images as benefiting from enhancement or otherwise. Finally, a novel windowed TRC mechanism based on monotonic regression ensures that the algorithm takes only 0.3 s to process a 10 MPix image on a 3 GHz Pentium.
Navigation Doppler lidar sensor for precision altitude and vector velocity measurements: flight test results (2011)

An all fiber Navigation Doppler Lidar (NDL) system is under development at NASA Langley Research Center (LaRC) for precision descent and landing applications on planetary bodies. The sensor produces high-resolution line of sight range, altitude above ground, ground relative attitude, and high precision velocity vector measurements. Previous helicopter flight test results demonstrated the NDL measurement concepts, including measurement precision, accuracies, and operational range. This paper discusses the results obtained from a recent campaign to test the improved sensor hardware, and various signal processing algorithms applicable to real-time processing. The NDL was mounted in an instrumentation pod aboard an Erickson Air-Crane helicopter and flown over various terrains. The sensor was one of several sensors tested in this field test by NASA's Autonomous Landing and Hazard Avoidance Technology (ALHAT) project.
Short contact time coal liquefaction. I. Techniques and product distributions. [2 refs] (1976)

Coal liquefaction, as exemplified by the solvent refined coal process, has been studied in a short contact time stirred reactor. The design and operation of the reactor system and work-up and analysis of the products are described in detail. Contact times as short as 0.5 min. have been obtained routinely. A synthetic recycle solvent has been developed. It matches the chemical properties of the true coal-derived recycle solvents, but can be distinguished from liquefaction products. From changes in the solvent composition, H-consumption by coal can be calculated. A series of runs with West Kentucky and Wyodak coals is described. Results presented include the product distributions as functions of time, temperature, H-donor ability of the solvent, nature of the gas, H-consumption, and oxygen removal. It is shown that little hydrogen consumption is required for dissolution and removal of approximately 40 percent of the organic oxygen and sulfur. The molecular weight distribution vs conversion reveals that the initial product appears to contain a significant high molecular weight (greater than 2000) component that is rapidly destroyed. High SRC yields are obtained early in the reaction; improvement of SRC quality is accompanied by a decrease in yield and a large increase in hydrogen consumption.
RAIM-FDE Revisited: A New Breakthrough In Availability Performance With<scp><i>nio</i></scp><i>RAIM</i>(Novel Integrity-Optimized RAIM) (2006)

ABSTRACT: The major shortcoming of Receiver Autonomous Integrity Monitoring Fault Detection and Exclusion (RAIM-FDE) is widely recognized to be its occasional lack of availability. There have been recent proposals to better balance accuracy and integrity levels such that the horizontal integrity limit for all satellite measurement geometries is lowered thereby improving system availability in the process. This paper presents a specific methodology called nioRAIM for accomplishing the proper balancing of position accuracy with integrity. It also shows that, for the Non-Precision Approach (NPA) phase of flight where baro-aiding is available, 50 percent of the unavailable geometries derived using standard RAIM-FDE can be salvaged when using nioRAIM. This paper also shows the added complexity involved in computing the nioRAIM algorithm, but a design is presented that is still amenable to real-time computation.
Efficient, flexible, and scalable inter-network spectrum sharing and communications in cognitive IEEE 802.22 networks (2008)

Although avoiding harmful interference to licensed incumbents is the prime concern of the system design for the emerging IEEE 802.22 standard, another key design challenge to cognitive radio based 802.22 systems is how to dynamically share the scarce spectrum among the collocated 802.22 network cells so that performance degradation, due to mutual co-channel interference, is effectively mitigated. This paper describes a distributed, cooperative, and real-time spectrum sharing protocol called On-Demand Spectrum Contention (ODSC) that employs interactive MAC messaging on an inter-network communication channel to provide efficient, scalable, and fair inter-network spectrum sharing among the coexisting 802.22 cells. Additionally, in order to support ODSC and other inter-network coordination functions in 802.22, we introduce a beacon-based inter-network communication protocol called the Beacon Period Framing (BPF) protocol that realizes a reliable, efficient, and scalable over-theair inter-network communication channel utilizing the occupied RF channels of the network cells.
A Monoclonal Antibody Based Capture ELISA for Botulinum Neurotoxin Serotype B: Toxin Detection in Food (2013)

Botulism is a serious foodborne neuroparalytic disease, caused by botulinum neurotoxin (BoNT), produced by the anaerobic bacterium Clostridium botulinum. Seven toxin serotypes (A-H) have been described. The majority of human cases of botulism are caused by serotypes A and B followed by E and F. We report here a group of serotype B specific monoclonal antibodies (mAbs) capable of binding toxin under physiological conditions. Thus, they serve as capture antibodies for a sandwich (capture) ELISA. The antibodies were generated using recombinant peptide fragments corresponding to the receptor-binding domain of the toxin heavy chain as immunogen. Their binding properties suggest that they bind a complex epitope with dissociation constants (KD's) for individual antibodies ranging from 10 to 48 × 10-11 M. Assay performance for all possible combinations of capture-detector antibody pairs was evaluated and the antibody pair resulting in the lowest level of detection (L.O.D.), ~20 pg/mL was determined. Toxin was detected in spiked dairy samples with good recoveries at concentrations as low as 0.5 pg/mL and in ground beef samples at levels as low as 2 ng/g. Thus, the sandwich ELISA described here uses mAb for both the capture and detector antibodies (binding different epitopes on the toxin molecule) and readily detects toxin in those food samples tested.
Absolute calibration of ultrasonic fields using a submersible electrostatic acoustic transducer. (1991)

The development of a liquid-immersible, megahertz-range, electrostatic acoustic transducer (ESAT) was previously reported [Cantrell etal., Rev. Sci. Instrum. 50, 31–33 (1979)]. The transducer basically consists of a thin conductive membrane stretched over an electrically isolated cylindrical electrode recessed approximately 10 μm from the membrane inner surface. A model recently developed to explain the frequency roll-off characteristics of the ESAT resulting from liquid-membrane coupling [J. H. Cantrell and W. T. Yost, Rev. Sci. Instrum. 60, 487–488 (1989)] together with a Thevenin equivalent substitutional circuit scheme permits absolute measurement of ultrasonic displacement amplitudes in the submicron range to be made with the ESAT. The geometry of the system allows straightforward correction for diffraction effects. ESAT calibration of ultrasonic tone bursts generated by broadband piezoelectric transducers immersed in water is reported. A fast Fourier transform-based technique using short unipolar voltage excitation for piezoelectric transducer calibration is discussed. [Work supported by NASA Office of Technology Utilization.]
Identification of Neisseria gonorrhoeae from primary cultures by a slide agglutination test (1978)

Hen antigonococcal lipopolysaccharide hen serum was used in a simple slide agglutination test for the identification of Neisseria gonorrhoeae from primary isolates.
Zebrafish intestinal fatty acid binding protein (I‐FABP) gene promoter drives gut‐specific expression in stable transgenic fish (2003)

Mammalian intestinal fatty acid-binding protein (I-FABP) is a small cytosolic protein and is thought to play a crucial role of intracellular fatty acid trafficking and metabolism in gut. To establish an in vivo system for investigating its tissue-specific regulation during zebrafish intestinal development, we isolated 5'-flanking sequences of the zebrafish L-FABP gene and used a transgenic strategy to generate gut-specific transgenic zebrafish with green/red fluorescent intestine. The 4.5-kb 5'-flanking sequence of zebrafish I-FABP gene was sufficient to direct fluorescent expression in intestinal tube, first observed in 3 dpf embryos and then continuously to the adult stage. This pattern of transgenic expression is consistent with the expression pattern of the endogenous gene. In all five transgenic lines 45-52% of the F2 inheritance rates were consistent with the ratio of Mendelian segregation. These fish can also provide a valuable resource of labeled adult intestinal cells for in vivo or in vitro studies. Finally, it is possible to establish an in vivo system using these fish for screening genes required for gut development. genesis 38:26-31, 2004.
DT‐01‐05: High Dose Donepezil with Solifenacin (CPC‐201) Improves Safety and Initial Efficacy in Alzheimer’s Disease (2016)

Cholinesterase inhibitors (ChEIs) remain the therapeutic mainstay for dementia of the Alzheimer’s type (DAT) despite dose-limiting adverse events (AEs) and modest efficacy. Nevertheless, PET studies indicate that ChEIs, at maximum tolerable dose (MTD), inhibit the target CNS enzyme by only about 30%, while non-clinical and clinical results suggest higher ChEI doses confer greater cognitive benefit. Moreover, Phase I studies supported hypothesis that co-administration of a peripheral anticholinergic reduces dose-limiting AEs, enabling the safe/tolerable use of higher ChEI doses and thus potentially improving antidementia efficacy. A phase IIa single-blind, crossover trial was conducted to further evaluate this hypothesis in 41 moderate (MMSE 10-20) DAT patients being successfully treated with 10 mg/day donepezil. The anticholinergic solifenacin was first titrated to 15 mg/day and then donepezil escalated to each patient’s MTD or protocol limit (40 mg/day). Patients continued at their MTD for 3 additional months. At the end of dose titration (week 14), the median MTD of donepezil (primary endpoint), given orally with solifenacin as CPC-201, increased to 40 mg/day (p <.0001; n = 33 in ITT population); 88% of patients reached this maximum allowable dose, which did not change significantly during following 3 months. Cognitive function, measured by the ADAS-cog scale at end of dose titration and during dose maintenance (weeks 18, 22 and 26 in n = 23 per protocol population) was consistently improved compared with baseline; adjustment for natural disease progression and the previously realized response to 10 mg donepezil (approximated from published RCT results) yielded a mean (± SEM) benefit of 5.4 ± .84 points (p < .05) compared to historic placebo (trial not powered for secondary efficacy measures). Combined Clinical Global Impression (CGI-I) scores from investigators and caregivers at 26 weeks averaged 3.1 ± .20 points, thus improving by .94 ± .20 points (p < .001; n = 16). At MTD, the frequency of gastrointestinal AEs declined by over 80% of that reported in trials of 10 and 23 mg donepezil. No drug-related drop-outs or SAEs, and no new AEs or evidence of solifenacin toxicity occurred. Attenuating donepezil AEs with soifenacin enables the safe/tolerable administration of higher ChEI doses that could improve antidementia efficacy.
Discovery of Iodinated Somatostatin Analogues Selective for hsst2 and hsst5 with Excellent Inhibition of Growth Hormone and Prolactin Release from Rat Pituitary Cells (2005)

Inhibition of growth hormone (GH) and prolactin (PRL) release from the anterior pituitary gland is mediated through somatostatin receptor subtypes sst2 and sst5. It has been found that somatostatin (SS) analogues that are selective for both receptor subtypes are more effective at inhibiting GH and PRL release than monospecific analogues alone. We synthesized several disulfide-bridged octapeptide SS analogues. Iodinated compounds 7, (4-amino-3-iodo)-d-Phe-c[Cys-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2, and 9, (4-amino-3-iodo)-d-Phe-c[Cys-(3-iodo)-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2, were as potent as somatostatin in binding at receptors hsst2 and hsst5 and inhibited GH and PRL release from rat pituitary cells as potently as somatostatin.