gebhart/patrepeval huggingface dataset:
The SNPlex genotyping system: a flexible and scalable platform for SNP genotyping. (2005)

We developed the SNPlex Genotyping System to address the need for accurate genotyping data, high sample throughput, study design flexibility, and cost efficiency. The system uses oligonucleotide ligation/polymerase chain reaction and capillary electrophoresis to analyze bi-allelic single nucleotide polymorphism genotypes. It is well suited for single nucleotide polymorphism genotyping efforts in which throughput and cost efficiency are essential. The SNPlex Genotyping System offers a high degree of flexibility and scalability, allowing the selection of custom-defined sets of SNPs for medium- to high-throughput genotyping projects. It is therefore suitable for a broad range of study designs. In this article we describe the principle and applications of the SNPlex Genotyping System, as well as a set of single nucleotide polymorphism selection tools and validated assay resources that accelerate the assay design process. We developed the control pool, an oligonucleotide ligation probe set for training and quality-control purposes, which interrogates 48 SNPs simultaneously. We present performance data from this control pool obtained by testing genomic DNA samples from 44 individuals. in addition, we present data from a study that analyzed 521 SNPs in 92 individuals. Combined, both studies show the SNPlex Genotyping system to have a 99.32% overall call rate, 99.95% precision, and 99.84% concordance with genotypes analyzed by TaqMan probe-based assays. The SNPlex Genotyping System is an efficient and reliable tool for a broad range of genotyping applications, supported by applications for study design, data analysis, and data management.
Paradoxical reaction to L-dopa in schizophrenic patients (1978)

The authors administered 6 g of L-dopa to 8 schizophrenic patients and 750 mg of chlorpromazine to 7 schizophrenic patients. Chlorpromazine showed only a modest advantage over L-dopa and only on some Brief Psychiatric Rating Scale factor scores, and at maximum dosage the thought disturbance factor score in the L-dopa-treated group was not worse than at baseline. The results suggest that L-dopa is associated more with toxic than with schizophreniform symptoms and that there is adaptation to its effects. The authors discuss implications of these findings for the dopamine hypothesis of schizophrenia.
Structure–Activity Relationship Studies on a Macrocyclic Agouti-Related Protein (AGRP) Scaffold Reveal Agouti Signaling Protein (ASP) Residue Substitutions Maintain Melanocortin-4 Receptor Antagonist Potency and Result in Inverse Agonist Pharmacology at the Melanocortin-5 Receptor (2017)

The melanocortin system consists of five reported receptors, agonists from the proopiomelanocortin gene transcript, and two antagonists, agouti-signaling protein (ASP) and agouti-related protein (AGRP). For both ASP and AGRP, the hypothesized Arg-Phe-Phe pharmacophores are on exposed β-hairpin loops. In this study, the Asn and Ala positions of a reported AGRP macrocyclic scaffold (c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro]) were explored with 14-compound and 8-compound libraries, respectively, to generate more potent, selective melanocortin receptor antagonists. Substituting diaminopropionic acid (Dap), DDap, and His at the Asn position yielded potent MC4R ligands, while replacing Ala with Ser maintained MC4R potency. Since these substitutions correlate to ASP loop residues, an additional Phe to Ala substitution was synthesized and observed to maintain MC4R potency. Seventeen compounds also possessed inverse agonist activity at the MC5R, the first report of this pharmacology. These findings are useful in developing molecular probes to study negative energy balance conditions and unidentified functions of the MC5R.
Scene and content analysis from multiple video streams (2002)

In this paper, we describe a framework for video analysis and a method to detect and understand the class of events we refer to as "split and merge events" from single or multiple video streams. We start with automatic detection of scene changes, including camera operations such as zoom, pan, tilts and scene cuts. For each new scene, camera calibration is performed, the scene geometry is estimated, to determine the absolute positions for each detected object. Objects in the video scenes are detected using an adaptive background subtraction method and tracked over consecutive frames. Objects are detected and tracked in a way to identify the key split and merge behaviors where one object splits into two or more objects and two or more objects merge into one object. We have identified split and merge behaviors as the key behavior components for several higher level activities such package drop-off, exchange between people, people getting out of cars or forming crowds etc. We embed the data about scenes, camera parameters, object features, positions into the video stream as metadata to correlate, compare and associate the results for several related scenes and achieve better video event understanding. This location for the detailed syntactic information allows it to be physically associated with the video itself and guarantees that analysis results will be preserved while in archival storage or when sub-clips are created for distribution to other users. We present some preliminary results over single and multiple video streams.
Using Data Postcompensation and Predistortion to Tolerate Cell-to-Cell Interference in MLC nand Flash Memory (2010)

With the appealing storage-density advantage, multilevel-per-cell (MLC) NAND Flash memory that stores more than 1 bit in each memory cell now largely dominates the global Flash memory market. However, due to the inherent smaller noise margin, the MLC NAND Flash memory is more subject to various device/circuit variability and noise, particularly as the industry is pushing the limit of technology scaling and a more aggressive use of MLC storage. Cell-to-cell interference has been well recognized as a major noise source responsible for raw-memory-storage reliability degradation. Leveraging the fact that cell-to-cell interference is a deterministic data-dependent process and can be mathematically described with a simple formula, we present two simple yet effective data-processing techniques that can well tolerate significant cell-to-cell interference at the system level. These two techniques essentially originate from two signal-processing techniques being widely used in digital communication systems to compensate communication-channel intersymbol interference. The effectiveness of these two techniques have been well demonstrated through computer simulations and analysis under an information theoretical framework, and the involved design tradeoffs are discussed in detail.
Source of heterogeneity in secreted interferon-<i>γ</i>. A study on products of translation <i>in vitro</i> (1990)

A cDNA clone coding for human interferon-gamma (IFN-gamma) was subcloned into a transcription-translation vector. When the mRNA transcribed in vitro was added to a rabbit reticulocyte-lysate system, two polypeptides were synthesized: one corresponding in Mr to pre-IFN-gamma (18,000) and one with a lower Mr (12,000) which corresponds to a polypeptide arising from incorrect initiation of translation. When microsomal vesicles isolated from dog pancreas or Chinese-hamster ovary (CHO) cells were added to the translation system, translocation of the pre-IFN-gamma occurred, as judged by protection from exogenous proteinases. The resultant changes in the Mr of the translation products were indicative of signal-peptide cleavage and heterogeneous core glycosylation. When translation products were treated with N-glycanase, the higher-Mr products were no longer observed, consistent with removal of all oligosaccharide side chains, leaving a single core polypeptide. Glycosylation of the synthesized protein yielded both singly and doubly glycosylated products compatible with the glycosylation variants seen in secreted IFN-gamma. Quantitative differences were seen in the relative amounts of singly and doubly glycosylated products synthesized by dog pancreatic compared with CHO-derived microsomes. These data indicate that the relative amounts of IFN-gamma glycosylation variants are determined at an early stage in protein synthesis and that product variants may occur when IFN-gamma is expressed in cells derived from different tissues.
Multiple (α-NH-ubiquitin)Protein Endoproteases in Cells (1989)

Ubiquitin is encoded as a variable, spacerless repeat of the gene terminating with an additional amino acid or as a gene coding for a single ubiquitin with a carboxyl-terminal extension of 52 to 80 amino acids. We report the identification and partial purification of enzymes that specifically hydrolyze the peptide bond between ubiquitin-ubiquitin conjugate (Ub-Ubase) or ubiquitin fusion proteins (Ub-Xase). The Ub-Ubase was separated from the Ub-Xase by dye-ligand-Sepharose chromatography. The Ub-Xase was purified further by affinity chromatography on ubiquitin-Sepharose. The fidelity of the endoprotease reaction was assessed by measuring the ability of the released ubiquitin to be activated by ubiquitin-activating enzyme (E1) which requires intact ubiquitin and by sequence analysis of the released carboxyl extension protein with 52 amino acids after endoproteolysis of human ubiquitin with 52-amino acid carboxyl extension. The failure of both Ub-Ubase and Ub-Xase to cleave a mutant ubiquitin-Gly-76----Ala-metallothionein showed that the endoproteases distinguish Gly-X from an Ala-X peptide bonds.
Activation of mammalian retinoid X receptors by the insect growth regulator methoprene. (1995)

We report that methoprene and its derivatives can stimulate gene transcription in vertebrates by acting through the retinoic acid-responsive transcription factors, the retinoid X receptors (RXRs). Methoprene is an insect growth regulator in domestic and agricultural use as a pesticide. At least one metabolite of methoprene, methoprene acid, directly binds to RXR and is a transcriptional activator in both insect and mammalian cells. Unlike the endogenous RXR ligand, 9-cis-retinoic acid, this activity is RXR-specific; the methoprene derivatives do not activate the retinoic acid receptor pathway. Methoprene is a juvenile hormone analog that acts to retain juvenile characteristics during insect growth, preventing metamorphosis into an adult, and it has been shown to have ovicidal properties in some insects. Thus, a pesticide that mimics the action of juvenile hormone in insects can also activate a mammalian retinoid-responsive pathway. This finding provides a basis through which the potential bioactivity of substances exposed to the environment may be reexamined and points the way for discovery of new receptor ligands in both insects and vertebrates.
Lipases and lipolysis in the human digestive tract: where do we stand? (2007)

A better knowledge of lipase structure and mode of action will help the development of new natural inhibitors with fewer secondary effects. More intensive research in protein engineering for recombinant lipase production and in clinical nutrition, together with careful evaluation of patients' individual needs is necessary.
Comparisons of LIPOXYGENASE3- and JASMONATE-RESISTANT4/6-Silenced Plants Reveal That Jasmonic Acid and Jasmonic Acid-Amino Acid Conjugates Play Different Roles in Herbivore Resistance of<i>Nicotiana attenuata</i>    (2007)

Whereas jasmonic acid (JA) and its amino acid conjugates, particularly JA-isoleucine (Ile), are known to play important roles in plant-herbivore interactions, whether other compounds also function as signals independently of JA-Ile and whether conjugates elicit systemic responses are unknown. To answer these questions, we simultaneously silenced JASMONATE-RESISTANT4 (JAR4) and JAR6, two functionally redundant enzymes in Nicotiana attenuata that conjugate JA to amino acids to produce plants (irjar4/6) with low levels of JA-Ile, JA-leucine (Leu), and JA-valine (Val; <16% of wild type). As expected, irjar4/6 plants are more vulnerable to herbivore attack, but only JA-Ile -- not JA-Leu or JA-Val -- applications restored the resistance of irjar4/6 plants, suggesting that JA-Leu and JA-Val do not mediate herbivore defense responses. Interestingly, the direct defense traits of irjar4/6 plants are significantly higher than those in LIPOXYGENASE3 (LOX3)-silenced (aslox3) plants, which are impaired in JA biosynthesis, and JA-Ile treatment could not fully restore the resistance of aslox3 plants. We thus conclude that JA, its precursors, or other metabolites complement the function of JA-Ile by eliciting a panoply of induced defenses. Similarly, transcriptional profiling of wild-type, irjar4/6, and aslox3 plants with microarrays demonstrated that JA-Ile and JA play overlapping yet distinct roles in herbivore defense. Analysis of transcripts in distal tissues demonstrated that JAR activity is essential in eliciting systemic responses. However, attempts to recover JA-(13)C(6)-Ile in systemic leaves and roots after feeding wounded leaves with (13)C(6)-Ile were unsuccessful, suggesting that JA-Ile is not a long-distance signal, but is rather synthesized after the arrival of an unknown mobile signal to systemic tissues.
Widespread skeletal metastatic potential of human lung cancer revealed by green fluorescent protein expression. (1998)

To understand the skeletal metastatic pattern of non-small cell lung cancer, we developed a stable high-expression green fluorescent protein (GFP) transductant of human lung cancer cell line H460 (H460-GFP). The GFP-expressing lung cancer was visualized to metastasize widely throughout the skeleton when implanted orthotopically in nude mice. H460 was transduced with the pLEIN retroviral expression vector containing the enhanced GFP and the neomycin (G418) resistance gene. A stable high GFP-expressing clone was selected in vitro using 800 microg/ml G418. Stable high-level expression of GFP was maintained in s.c.-growing tumors formed after injecting H460-GFP cells in nude mice. To use H460-GFP for visualization of metastasis, fragments of s.c.-growing H460-GFP tumors were implanted by surgical orthotopic implantation in the left lung of nude mice. Subsequent micrometastases were visualized by GFP fluorescence in the contralateral lung, plural membrane, and widely throughout the skeletal system including the skull, vertebra, femur, tibia, pelvis, and bone marrow of the femur and tibia. The use of GFP-expressing H460 cells transplanted by surgical orthotopic implantation revealed the extensive metastatic potential of lung cancer in particular to widely disseminated sites throughout the skeleton. This new metastatic model can play a critical role in the study of the mechanism of skeletal and other metastasis in lung cancer and in screening of therapeutics that prevent or reverse this process.
Didaktische Dichtung (1998)

Zusammenhängend und öffentlich hat sich G. erst im hohen Alter zur didaktischen Poesie geäußert: in einem kurzen Aufsatz mit dem Titel Über das Lehrgedicht, der 1827 im 6. Band der Zeitschrift lieber Kunst und Alteration erschien (WA 1,41.2, S. 225-227). Voraus und nebenher gingen gelegentliche Bemerkungen: »Lehrgedichte oder beschreibende« seien nicht gut zu vertonen (JA 35, S.314); Verse, die zu »Tugend, Tauglichkeit, […], Sittlichkeit« ermunterten, sollten »nicht didactisch, sondern gemüthlich und herzerregend« sein (WA I, 42.2, S.415); Schriftsteller aus dem Volk, sog. »Naturpoeten«, hätten eine Neigung in Richtung auf das »Didaktische, Belehrende, Sittenverbessernde« (WA I, 42.1, S. 97). Anlaß zu G.s eingangs erwähntem Aufsatz bot Friedrich Konrad Griepenkerls Lehrbuch der Ästhetik von 1827, worin nach traditioneller Art neben anderen Dichtungsgattungen auch der Lehrdichtung ihr Recht eingeräumt wurde.
High‐speed gas chromatography using an on‐column thermal desorption modulator (1989)

Abstract A short, narrow‐bore (50 μm) column with an on‐column thermal desorp‐ tion modulator provides a technically simple and reliable method to generate high‐ speed gas chromatograms. A thermal desorption modulator prepared on the column but operated at a lower temperature functions as a sample introduction device. The modulator portion of the column extends outside of the oven and is at room temperature. A sample stream flows continuously into the modulator and through it into the column. Retained sample is released from the modulator by an electricaliy generated temperature pulse and carried into the column as a concentration pulse analogous to a sharp injecfion. Because the modulator is part of the column, no external injector is needed, and the volume of the concentration pulse is automatically appropriate for the column diameter. A series of chromatograms can be generated from a continuously flowing sample stream by applying a series of temperature pulses to the modulator. The narrow‐bore column is highly efficient and generates chromatograms with total retention times as short as 1 s. Chromatographic efficiency reaches the column's the oretical limit at very high carrier gas linear velocity. Measured terminal band lengths are shorter than the length of the modulator because the thermal gradient between modulator and column focuses bands as they enter the column. Band durations are less than the modulator thermal pulse duration because sample substances are released from the modulator stationary phase and carried onto the column during a small part of the temperature ramp.
Detailed description of four YAC contigs representing 17 Mb of chromosome 4 of <i>Arabidopsis thaliana</i> ecotype Columbia (1996)

The detailed arrangement of 563 YAC clones comprising four contigs covering approximately 17 Mbp of chromosome 4 is presented. YAC clones were positioned relative to each other and to markers by taking into account marker and end fragment hybridization data and the sizes of all YAC clones. This analysis made it possible to estimate physical distances between the majority of chromosome 4 markers. It also identified a relatively large number of YAC clones containing chimaeric inserts. The YAC contig map of the Columbia ecotype presents an important resource for map-based cloning experiments, rapid mapping of DNA sequences and large-scale genomic sequencing programs.
Topical butyrate improves efficacy of 5‐ASA in refractory distal ulcerative colitis: results of a multicentre trial (2003)

The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.
<i>Salmonella</i> effectors within a single pathogenicity island are differentially expressed and translocated by separate type III secretion systems (2002)

Pathogenicity islands (PAIs) are large DNA segments in the genomes of bacterial pathogens that encode virulence factors. Five PAIs have been identified in the Gram-negative bacterium Salmonella enterica. Two of these PAIs, Salmonella pathogenicity island (SPI)-1 and SPI-2, encode type III secretion systems (TTSS), which are essential virulence determinants. These 'molecular syringes' inject effectors directly into the host cell, whereupon they manipulate host cell functions. These effectors are either encoded with their respective TTSS or scattered elsewhere on the Salmonella chromosome. Importantly, SPI-1 and SPI-2 are expressed under distinct environmental conditions: SPI-1 is induced upon initial contact with the host cell, whereas SPI-2 is induced intracellularly. Here, we demonstrate that a single PAI, in this case SPI-5, can encode effectors that are induced by distinct regulatory cues and targeted to different TTSS. SPI-5 encodes the SPI-1 TTSS translocated effector, SigD/SopB. In contrast, we report that the adjacently encoded effector PipB is part of the SPI-2 regulon. PipB is translocated by the SPI-2 TTSS to the Salmonella-containing vacuole and Salmonella-induced filaments. We also show that regions of SPI-5 are not conserved in all Salmonella spp. Although sigD/sopB is present in all Salmonella spp., pipB is not found in Salmonella bongori, which also lacks a functional SPI-2 TTSS. Thus, we demonstrate a functional and regulatory cross-talk between three chromosomal PAIs, SPI-1, SPI-2 and SPI-5, which has significant implications for the evolution and role of PAIs in bacterial pathogenesis.
FGF21 Is Not a Major Mediator for Bone Homeostasis or Metabolic Actions of PPARα and PPARγ Agonists (2016)

Results of prior studies suggest that fibroblast growth factor 21 (FGF21) may be involved in bone turnover and in the actions of peroxisome proliferator-activated receptor (PPAR) α and γ in mice. We have conducted independent studies to examine the effects of FGF21 on bone homeostasis and the role of FGF21 in PPARα and γ actions. High-fat-diet-induced obesity (DIO) mice were administered vehicle or recombinant human FGF21 (rhFGF21) intraperitoneally at 0 (vehicle), 0.1, 1, and 3 mg/kg daily for 2 weeks. Additional groups of DIO mice received water or 10 mg/kg rosiglitazone daily. Mice treated with rhFGF21 or rosiglitazone showed expected metabolic improvements in glucose, insulin, and lipid levels. However, bone loss was not detected in rhFGF21-treated mice by dual-energy X-ray absorptiometry (DXA), micro-CT, and histomorphometric analyses. Mineral apposition rate, a key bone formation parameter, was unchanged by rhFGF21, while significantly decreased by rosiglitazone in DIO mice. Bone resorption markers, OPG/RANKL mRNA expression, and histological bone resorption indices were unchanged by rhFGF21 or rosiglitazone. Bone marrow fat was unchanged by rhFGF21, while increased by rosiglitazone. Furthermore, FGF21 knockout mice did not show high bone mass phenotype. Treatment with PPARα or PPARγ agonists caused similar metabolic effects in FGF21 knockout and wild-type mice. These results contrast with previous findings and suggest that FGF21 is not critical for bone homeostasis or actions of PPARα and PPARγ. © 2016 American Society for Bone and Mineral Research.
Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog (1995)

We have studied the three-dimensional arrangement of ventricular muscle cells and the associated extracellular connective tissue matrix in dog hearts. Four hearts were potassium-arrested, excised, and perfusion-fixed at zero transmural pressure. Full-thickness segments were cut from the right and left ventricular walls at a series of precisely located sites. Morphology was visualized macroscopically and with scanning electron microscopy in 1) transmural planes of section and 2) planes tangential to the epicardial surface. The appearance of all specimens was consistent with an ordered laminar arrangement of myocytes with extensive cleavage planes between muscle layers. These planes ran radially from endocardium toward epicardium in transmural section and coincided with the local muscle fiber orientation in tangential section. Stereological techniques were used to quantify aspects of this organization. There was no consistent variation in the cellular organization of muscle layers (48.4 +/- 20.4 microns thick and 4 +/- 2 myocytes across) transmurally or in different ventricular regions (23 sites in 6 segments), but there was significant transmural variation in the coupling between adjacent layers. The number of branches between layers decreased twofold from subepicardium to midwall, whereas the length distribution of perimysial collagen fibers connecting muscle layers was greatest in the midwall. We conclude that ventricular myocardium is not a uniformly branching continuum but a laminar hierarchy in which it is possible to identify three axes of material symmetry at any point.