gebhart/patrepeval huggingface dataset:
Actinomycin D as a novel SH2 domain ligand inhibits Shc/Grb2 interaction in B104‐1‐1 (neu*‐transformed NIH3T3) and SAA (hEGFR‐overexpressed NIH3T3) cells (1999)

Actinomycins, a family of bicyclic chromopeptide lactones with strong antineoplastic activity, were screened as inhibitors of Shc/Grb2 interaction in in vitro assay systems. To investigate the effects of actinomycin D on Shc/Grb2 interaction in cell-based experiments, we used SAA (normal hEGFR-overexpressed NIH3T3) cells and B104-1-1 (neu*-transformed NIH3T3) cells, because a large number of the Shc/Grb2 complexes were detected. Associated protein complexes containing Shc were immunoprecipitated from actinomycin D-treated cell lysates with polyclonal anti-Shc antibody. Then the association with Grb2 was assessed by immunoblotting with monoclonal anti-Grb2 antibody. The result of the immunoblotting experiment revealed that actinomycin D inhibited Shc/Grb2 interaction in a dose-dependent manner in both B104-1-1 and EGF-stimulated SAA cells. The inhibition of Shc/Grb2 interaction by actinomycin D in B104-1-1 cells also reduced tyrosine phosphorylation of MAP kinase (Erk1/Erk2), one of the major components in the Ras-MAP kinase signaling pathway. These results suggest that actinomycin D could be a non-phosphorylated natural and cellular membrane-permeable SH2 domain antagonist.
Checkpoints: Controls That Ensure the Order of Cell Cycle Events (1989)

The events of the cell cycle of most organisms are ordered into dependent pathways in which the initiation of late events is dependent on the completion of early events. In eukaryotes, for example, mitosis is dependent on the completion of DNA synthesis. Some dependencies can be relieved by mutation (mitosis may then occur before completion of DNA synthesis), suggesting that the dependency is due to a control mechanism and not an intrinsic feature of the events themselves. Control mechanisms enforcing dependency in the cell cycle are here called checkpoints. Elimination of checkpoints may result in cell death, infidelity in the distribution of chromosomes or other organelles, or increased susceptibility to environmental perturbations such as DNA damaging agents. It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose special problems for the fidelity of embryonic cell division.
Obtaining Spectrum Matching Time Series Using a Reweighted Volterra Series Algorithm (RVSA) (2014)

In this paper, we introduce a novel algorithm for morphing any accelerogram into a spectrum matching one. First, the seed time series is re-expressed as a discrete Volterra series. The first-order Volterra kernel is estimated by amultilevel wavelet decomposition using the stationary wavelet transform. Second, the higher-order Volterra kernels are estimated using a complete multinomial mixing of the first-order kernel functions. Finally, the weighting of every term in this Volterra series is optimally adapted using a Levenberg-Marquardt algorithm such that the modified time series matches any target response spectrum. Comparisons are made using the SeismoMatch algorithm, and this reweighted Volterra series algorithm is demonstrated to be considerably more robust,matching the target spectrum more faithfully. This is achievedwhile qualitatively maintaining the original signal's nonstationary statistics, such as general envelope, time location of large pulses, and variation of frequency content with time.
Regulation of factor IXa in vitro in human and mouse plasma and in vivo in the mouse. Role of the endothelium and the plasma proteinase inhibitors. (1984)

The regulation of human Factor IXa was studied in vitro in human and mouse plasma and in vivo in the mouse. In human plasma, approximately 60% of the 125I-Factor IXa was bound to antithrombin III (ATIII) by 2 h, with no binding to alpha 2-macroglobulin or alpha 1-proteinase inhibitor, as assessed by gel electrophoresis and IgG- antiproteinase inhibitor-Sepharose beads. In the presence of heparin, virtually 100% of the 125I-Factor IXa was bound to ATIII by 1 min. The distribution of 125I-Factor IXa in mouse plasma was similar. The clearance of 125I-Factor IXa was rapid (50% clearance in 2 min) and biphasic and was inhibited by large molar excesses of ATIII-thrombin and alpha 1-proteinase inhibitor-trypsin, but not alpha 2-macro-globulin-trypsin; it was also inhibited by large molar excesses of diisopropylphosphoryl - (DIP-) Factor Xa, DIP-thrombin, and Factor IX, but not by prothrombin or Factor X. The clearance of Factor IX was also rapid (50% clearance in 2.5 min) and was inhibited by a large molar excess of Factor IX, but not by large molar excesses of Factor X, prothrombin, DIP-Factor Xa, or DIP-thrombin. Electrophoresis and IgG- antiproteinase inhibitor-Sepharose bead studies confirmed that by 2 min after injection into the murine circulation, 60% of the 125I-Factor IXa was bound to ATIII. Organ distribution studies with 125I-Factor IXa demonstrated that most of the radioactivity was in the liver. These studies suggest that Factor IXa binds to at least two classes of binding sites on endothelial cells. One site apparently recognizes both Factors IX and IXa, but not Factor X, Factor Xa, prothrombin, or thrombin. The other site recognizes thrombin, Factor Xa, and Factor IXa, but not the zymogen forms of these clotting factors. After this binding, Factor IXa is bound to ATIII and the complex is cleared from the circulation by hepatocytes.
Bottom-up approach to engineer two covalent porphyrinic frameworks as effective catalysts for selective oxidation (2014)

Two kinds of novel functional covalent organic frameworks were assembled with the porphyrin building block and terephthalaldehyde or squaric acid <italic>via</italic> bottom-up approach.
Selective thyroid hormone receptor-β activation: A strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability (2003)

Few treatments for obesity exist and, whereas efficacious therapeutics for hyperlipidemia are available, further improvements are desirable. Thyroid hormone receptors (TRs) regulate both body weight and cholesterol levels. However, thyroid hormones also have deleterious effects, particularly on the heart. The TR beta subtype is involved in cholesterol lowering and possibly elevating metabolic rate, whereas TR alpha appears to be more important for control of heart rate (HR). In the current studies, we examined the effect of TR beta activation on metabolic rate and HR with either TR alpha 1-/- mice or the selective TR beta agonist KB-141 in mice, rats, and monkeys. 3,5,3'-triiodi-l-thyronine (T3) had a greater effect on increasing HR in WT than in TR alpha-/- mice (ED15 values of 34 and 469 nmol/kg/day, respectively). T3 increased metabolic rate [whole body oxygen consumption (MVO2)] in both WT and TR alpha-/- mice, but the effect in the TR alpha 1-/- mice at the highest dose was half that of the WT mice. Thus, stimulation of MVO2 is likely due to both TR alpha and -beta. T3 had equivalent potency for cholesterol reduction in WT and TR alpha-/- mice. KB-141 increased MVO2 with selectivities of 16.5- and 11.2-fold vs. HR in WT and TR alpha 1-/- mice, respectively. KB-141 also increased MVO2 with a 10-fold selectivity and lowered cholesterol with a 27-fold selectivity vs. HR in rats. In primates, KB-141 caused significant cholesterol, lipoprotein (a), and body-weight reduction (up to 7% after 1 wk) with no effect on HR. TR beta-selective agonists may constitute a previously uncharacterized class of drugs to treat obesity, hypercholesterolemia, and elevated lipoprotein (a).
Evidence for a frizzled-mediated wnt pathway required for zebrafish dorsal mesoderm formation (1998)

We have used zebrafish as a model system for the study of vertebrate dorsoventral patterning. We isolated a maternally expressed and dorsal organizer localized member of the frizzled family of wnt receptors. Wild-type and dominant, loss-of-function molecules in misexpression studies demonstrate frizzled function is necessary and sufficient for dorsal mesoderm specification. frizzled activity is antagonized by the action of GSK-3, and we show GSK-3 is also required for zebrafish dorsal mesoderm formation. frizzled cooperatively interacts with the maternally encoded zebrafish wnt8 protein in dorsal mesodermal fate determination. This frizzled -mediated wnt pathway for dorsal mesoderm specification provides the first evidence for the requirement of a wnt-like signal in vertebrate axis determination.
A single chain Fv derived from a filamentous phage library has distinct tumour targeting advantages over one derived from a hybridoma (1995)

Single-chain antibodies (scFvs) can be derived from a monoclonal antibody (MAb) or produced directly using filamentous phage technology, where antibodies with desired binding and purification characteristics can be readily selected from libraries. To test the hypothesis that the latter approach is more useful, we compared 2 anti-carcinoembryonic antigen (CEA) scFvs produced by these 2 different approaches. Our study showed that, both in the purification process and in the biodistribution pattern, MFE-23, produced by filamentous phage technology, gave favourable results compared to A5-SC, which is derived from the A5B7 MAb. This indicates the value of the filamentous phage approach for obtaining tumour-targeting scFvs.
Programming Microsoft® DirectShow® for Digital Video and Television (2003)

From desktop to television screen, deliver broadcast-ready digital video with DirectShow-the Microsoft DirectX streaming API integrated in the Windows operating system. Digital video expert and VRML creator Mark Pesce walks you through core DirectShow capabilities for capturing, editing, and rendering media-demonstrating basic to advanced techniques for producing studio-quality results. Whether you're looking to add simple playback to an application or create your own movies and features, you'll get the tools, guidance, and ready-to-use media clips you need to get started now. Learn how to: * Use the GraphEdit design tool to rapidly prototype applications * Write your own source, transform, and renderer filters * Capture audio and video from Webcams, digital video cameras, and TV tuners * Compress digital video streams onto disk * Place clips and tracks on a timeline with DirectShow Editing Services * Merge multiple video streams with the Video Mixing Renderer (VMR) * Synchronize audio and video * Create simple programs to play MP3, WAV, MIDI, AVI, and Microsoft Windows Media files * Use DirectX Media Objects (DMOs) for faster, lightweight development of effects, encoders, and decoders * Extend DirectShow with AVIs and Windows Media Format CD inside Includes reusable media and code samples CD features: * Microsoft DirectX 9.0 Software Development Kit (SDK) and documentation * Music, a movie short, and other video and audio samples * All the book's programs and code
Farnesyltransferase Inhibitors: A Detailed Chemical View on an Elusive Biological Problem (2008)

Farnesyltransferase (FTase) is a zinc enzyme that has been the subject of particular attention in anti-cancer research. This enzyme promotes the addition of a farnesyl group from farnesyl diphosphate (FPP) to a cysteine residue of a protein substrate containing a typical -CAAX motif at the carboxyl terminus. Initial interest in FTase inhibition was prompted by the finding that farnesylation was absolutely required for the oncogenic forms of ras proteins to transform cells, as ras proteins have been implicated in around 30% of all human cancers. This discovery led to frenetic search for FTase inhibitors (FTIs), with more than 400 patents registered in less than a decade. However, despite the very promising initial results, the outcome of Phase II and Phase III clinical trials was, is general, rather disappointing, with the most advanced FTIs failing to demonstrate anti-tumor activity in ras dependent cancers, presumably because K-ras, the most frequently mutated form of ras in human cancers, is able to bypass FTI blockade through cross-prenylation by the related enzyme geranylgeranyltransferase I (GGTase I). Surprisingly, several of these compounds were later shown to have anti-tumor activity against non-ras dependent cancers, launching the grounds for a new and exciting era in FTIs research and development, although the precise target for the FTIs activity of these compounds still remains unknown. This review reports the recent progress in the field, presenting a comprehensive summary of the most promising FTIs, in terms of their chemical structure and properties, taking into account the topology of the enzyme's active-site, and the most recent mechanistic results on the catalytic activity of FTase, both at the theoretical and mechanistic level. These features are presented in close linking with the available results on the biological activity of these inhibitors, and with the outcome of the most recent clinical trials.
Gamma processing technology: an alternative technology for terminal sterilization of parenterals. (1995)

This paper will outline the advantages of utilizing gamma radiation as a means for terminally sterilizing parenterals and other pharmaceutical products. The factors which must be evaluated in order to qualify a product for radiation sterilization will be detailed. It will also compare the characteristics of this method with other technologies currently available. The highest SAL can be achieved by combining a knowledge of the microbial quality of the raw materials, and the manufacturing environment with a formulation designed to promote the most radiation stable form of the product.
Intravitreal steroids versus observation for macular edema secondary to central retinal vein occlusion (2009)

There is inadequate evidence for the use of intravitreal steroids for CRVO-ME due to a paucity of RCTs and well-designed observational studies on the topic; therefore, it is still an experimental procedure.
Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation (2013)

Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all. Distribution of the hypermethylation among cancer samples was non-random, which implied existence of a subset of preferentially methylated papillary thyroid cancer. Among 25 frequently methylated genes, methylation status of six genes (HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, HOXA7) was validated quantitatively by pyrosequencing. Epigenetic silencing of these genes in methylated papillary thyroid cancer cell lines was confirmed by gene re-expression following treatment with 5-aza-2'-deoxycytidine and trichostatin A, and detected by real-time RT-PCR. Methylation of these six genes was validated by analysis of additional 20 papillary thyroid cancer and 10 normal samples. Among the 34 cancer samples in total, 26 cancer samples with preferential methylation were significantly associated with mutation of BRAF/RAS oncogene (P = 0.04, Fisher's exact test). Thus, we identified new genes with frequent epigenetic hypermethylation in papillary thyroid cancer, two subsets of either preferentially methylated or hardly methylated papillary thyroid cancer, with a concomitant occurrence of oncogene mutation and gene methylation. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer.
Accuracy of Portable Blood Glucose Monitoring: Effect of Glucose Level and Prandial State (1991)

Glucose was determined on capillary and venous blood samples from 274 adult diabetics by three different methodologies: the Glucoscan 2000 and Accu-Check II portable glucose meters (capillary) and the Kodak Ektachem 700 analyzer (venous). Both glucose meters correlated significantly with the Ektachem results. A significant positive bias was found for the Glucoscan compared with Ektachem, not found with the Accu-Check II. The Accu-Check performed better than the Glucoscan at venous plasma glucose levels less than 1 g/L. The mean error of Glucoscan determinations was significantly greater and biased positive when the measurement was performed within 4 hours of eating, whereas no such effect was seen with Accu-Check error. Multiple regression analysis revealed that the Glucoscan measurement was independently influenced by both venous plasma glucose and prandial state, whereas the Accu-Check II measurement was not dependent on either variable. The within-run precision for both glucose meters were comparable.
Structure-Activity Relationships for Inhibition of Type 1 and 2 Human 5.alpha.-Reductase and Human Adrenal 3.beta.-Hydroxy-.DELTA.5-steroid Dehydrogenase/3-Keto-.DELTA.5-steroid Isomerase by 6-Azaandrost-4-en-3-ones: Optimization of the C17 Substituent (1995)

A variety of C17 amide-substituted 6-azaandrost-4-en-3-ones were prepared and tested versus human type 1 and 2 steroid 5 alpha-reductase (5AR) and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase (3BHSD) in order to optimize potency versus both isozymes of 5AR and selectivity versus 3BHSD. Two series of potent and selective C17 amides were discovered, 2,5-disubstituted anilides and (arylcycloalkyl)amides. Compounds from each series with picomolar IC50's versus human type 2 5AR and low nanomolar to picomolar IC50's versus human type 1 5AR possessing 100-500-fold selectivity versus 3BHSD were identified. A conformational model to predict 3BHSD potency was developed which could rationalize 3BHSD potency within three different series of compounds. Evaluation of some optimal compounds from this series in a chronic castrated rat model of 5AR inhibitor induced prostate involution, and pharmacokinetic measurements identified compounds (9, 12, 16, and 29) with good in vivo efficacy and half-life in the dog. An intact rat model of in vivo selectivity for 5AR versus 3BHSD inhibition was also developed. Dual inhibitors of both human 5AR's may show advantages over type 2 selective 5AR inhibitors, such as finasteride (1), in the treatment of disease states which depend upon dihydrotestosterone.
Discriminative prediction of mammalian enhancers from DNA sequence (2011)

Accurately predicting regulatory sequences and enhancers in entire genomes is an important but difficult problem, especially in large vertebrate genomes. With the advent of ChIP-seq technology, experimental detection of genome-wide EP300/CREBBP bound regions provides a powerful platform to develop predictive tools for regulatory sequences and to study their sequence properties. Here, we develop a support vector machine (SVM) framework which can accurately identify EP300-bound enhancers using only genomic sequence and an unbiased set of general sequence features. Moreover, we find that the predictive sequence features identified by the SVM classifier reveal biologically relevant sequence elements enriched in the enhancers, but we also identify other features that are significantly depleted in enhancers. The predictive sequence features are evolutionarily conserved and spatially clustered, providing further support of their functional significance. Although our SVM is trained on experimental data, we also predict novel enhancers and show that these putative enhancers are significantly enriched in both ChIP-seq signal and DNase I hypersensitivity signal in the mouse brain and are located near relevant genes. Finally, we present results of comparisons between other EP300/CREBBP data sets using our SVM and uncover sequence elements enriched and/or depleted in the different classes of enhancers. Many of these sequence features play a role in specifying tissue-specific or developmental-stage-specific enhancer activity, but our results indicate that some features operate in a general or tissue-independent manner. In addition to providing a high confidence list of enhancer targets for subsequent experimental investigation, these results contribute to our understanding of the general sequence structure of vertebrate enhancers.
<title>Modeling video temporal relationships in an object database management system</title> (1997)

One of the key aspects of videos is the temporal relationship between video frames. In this paper we propose a tree-based model for specifying the temporal semantics of video data. We present a unique way of integrating our video model into an object database management system which has rich multimedia temporal operations. We further show how temporal histories are used to model video data, explore the video object base using object-oriented techniques. Such a seamless integration gives a uniform interface to end users. The integrated video object base management systems supports a broad range of temporal queries.
Preparation and properties of pure alkyl glucosides, maltosides and maltotriosides (1984)

Abstract Alkyl β ‐D‐glycopyranosides composed of glucose, maltose or maltotriose attached to alkyl groups having from 4 to 18 carbon atoms were synthesized and tested for their physical and functional properties. Values are given for melting points, optical rotations, detergencies, critical micelle concentrations, surface tensions, interfacial surface tensions, Draves wetting tests and Ross Miles foam tests. Results show that maximum cleaning was obtained with maltosides attached to straight chain alkyl groups having from 12 to 15 carbon atoms.
3-TFT active pixel sensor with correlated double sampling readout circuit for real-time medical x-ray imaging (2006)

This paper presents a current-programmed, current-output active pixel sensor (APS) suitable for real time X-ray imaging (e.g., fluoroscopy) using hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) technology and an appropriate CMOS readout circuit. The proposed pixel circuit can successfully compensate for characteristic variations such as mobility and threshold voltage shift in a-Si:H TFTs. The proposed readout circuit exploits correlated double sampling (CDS) technique not only for reducing the offset current and low frequency noise, but also to reduce the effect of fixed-pattern noise (FPN) on the array operation. The on-pixel amplification reduces the input referred noise to levels that can satisfy the strict requirements for low noise digital fluoroscopy
An estrogen receptor‐based transactivator XVE mediates highly inducible gene expression in transgenic plants (2000)

We have developed an estrogen receptor-based chemical-inducible system for use in transgenic plants. A chimeric transcription activator, XVE, was assembled by fusion of the DNA-binding domain of the bacterial repressor LexA (X), the acidic transactivating domain of VP16 (V) and the regulatory region of the human estrogen receptor (E; ER). The transactivating activity of the chimeric XVE factor, whose expression was controlled by the strong constitutive promoter G10-90, was strictly regulated by estrogens. In transgenic Arabidopsis and tobacco plants, estradiol-activated XVE can stimulate expression of a GFP reporter gene controlled by the target promoter, which consists of eight copies of the LexA operator fused upstream of the -46 35S minimal promoter. Upon induction by estradiol, GFP expression levels can be eightfold higher than that transcribed from a 35S promoter, whereas the uninduced controls have no detectable GFP transcripts, as monitored by Northern blot analysis. Neither toxic nor adverse physiological effects of the XVE system have been observed in transgenic Arabidopsis plants under all the conditions tested. The XVE system thus appears to be a reliable and efficient chemical-inducible system for regulating transgene expression in plants.