gebhart/patrepeval huggingface dataset:
Knowledge-based visualization of time-oriented clinical data. (1998)

We describe a domain-independent framework (KNAVE) specific to the task of interpretation, summarization, visualization, explanation, and interactive exploration in a context-sensitive manner through time-oriented raw clinical data and the multiple levels of higher-level, interval-based concepts that can be abstracted from these data. The KNAVE exploration operators, which are independent of any particular clinical domain, access a knowledge base of temporal properties of measured data and interventions that is specific to the clinical domain. Thus, domain-specific knowledge underlies the domain-independent semantics of the interpretation, visualization, and exploration processes. Initial evaluation of the KNAVE prototype by a small number of users with variable clinical and informatics training has been encouraging.
Potential neuroprotective role of astroglial exosomes against smoking-induced oxidative stress and HIV-1 replication in the central nervous system (2018)

HIV-1-infected smokers are at risk of oxidative damage to neuronal cells in the central nervous system by both HIV-1 and cigarette smoke. Since neurons have a weak antioxidant defense system, they mostly depend on glial cells, particularly astrocytes, for protection against oxidative damage and neurotoxicity. Astrocytes augment the neuronal antioxidant system by supplying cysteine-containing products for glutathione synthesis, antioxidant enzymes such as SOD and catalase, glucose for antioxidant regeneration via the pentose-phosphate pathway, and by recycling of ascorbic acid. Areas covered: The transport of antioxidants and energy substrates from astrocytes to neurons could possibly occur via extracellular nanovesicles called exosomes. This review highlights the neuroprotective potential of exosomes derived from astrocytes against smoking-induced oxidative stress, HIV-1 replication, and subsequent neurotoxicity observed in HIV-1-positive smokers. Expert opinion: During stress conditions, the antioxidants released from astrocytes either via extracellular fluid or exosomes to neurons may not be sufficient to provide neuroprotection. Therefore, we put forward a novel strategy to combat oxidative stress in the central nervous system, using synthetically developed exosomes loaded with antioxidants such as glutathione and the anti-aging protein Klotho.
An electronically addressed spatial light modulator (1989)

Coherent optical data processing is recognised to be a natural solution to certain information processing problems. Attempts to exploit the benefits of optical processing are limited by the quality of available Spatial Light Modulators. Spatial Light Modulators are devices which controllably impress information onto the amplitude or phase of an optical wavefront. They are used both to input data into an opticaI system and as modulating elements within the system (often in the Fourier plane of a Fourier transform processor). This thesis describes the successful development of an electronically addressed spatial light modulator using liquid crystal as the light modulating material and a silicon integrated circuit as the addressing medium. It is a pixelated binary spatial light modulator operating in reflection. Each pixel contains a memory element which stores the programmed logical state of the pixel. The addressing and pixel circuits were fabricated in a 1.5m nMOS technology on a 10 mm square chip. The pixels are arranged on a square array containing 50 x 50 elements. The liquid crystal was configured to modulate the light amplitude using the hybrid field effect in a nematic liquid crystal. The spatial light modulator is used as a Fourier plane filter in a coherent optical processing system. Its performance is assessed and the direction of future research into this type of spatial light modulator is discussed.
Human Tyrosyl-tRNA Synthetase Shares Amino Acid Sequence Homology with a Putative Cytokine (1997)

To test the hypothesis that tRNATyr recognition differs between bacterial and human tyrosyl-tRNA synthetases, we sequenced several clones identified as human tyrosyl-tRNA synthetase cDNAs by the Human Genome Project. We found that human tyrosyl-tRNA synthetase is composed of three domains: 1) an amino-terminal Rossmann fold domain that is responsible for formation of the activated E.Tyr-AMP intermediate and is conserved among bacteria, archeae, and eukaryotes; 2) a tRNA anticodon recognition domain that has not been conserved between bacteria and eukaryotes; and 3) a carboxyl-terminal domain that is unique to the human tyrosyl-tRNA synthetase and whose primary structure is 49% identical to the putative human cytokine endothelial monocyte-activating protein II, 50% identical to the carboxyl-terminal domain of methionyl-tRNA synthetase from Caenorhabditis elegans, and 43% identical to the carboxyl-terminal domain of Arc1p from Saccharomyces cerevisiae. The first two domains of the human tyrosyl-tRNA synthetase are 52, 36, and 16% identical to tyrosyl-tRNA synthetases from S. cerevisiae, Methanococcus jannaschii, and Bacillus stearothermophilus, respectively. Nine of fifteen amino acids known to be involved in the formation of the tyrosyl-adenylate complex in B. stearothermophilus are conserved across all of the organisms, whereas amino acids involved in the recognition of tRNATyr are not conserved. Kinetic analyses of recombinant human and B. stearothermophilus tyrosyl-tRNA synthetases expressed in Escherichia coli indicate that human tyrosyl-tRNA synthetase aminoacylates human but not B. stearothermophilus tRNATyr, and vice versa, supporting the original hypothesis. It is proposed that like endothelial monocyte-activating protein II and the carboxyl-terminal domain of Arc1p, the carboxyl-terminal domain of human tyrosyl-tRNA synthetase evolved from gene duplication of the carboxyl-terminal domain of methionyl-tRNA synthetase and may direct tRNA to the active site of the enzyme.
Nuclear RNA-seq of single neurons reveals molecular signatures of activation (2016)

Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application of single-cell techniques to study the transcriptome of activated neurons can offer insight into molecular dynamics associated with differential neuronal responses to a given experience. Through evaluation of common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully recapitulates transcriptional patterns associated with experience-driven induction of activity, including immediate early genes (IEGs) such as Fos, Arc and Egr1. SnRNA-seq of mouse dentate granule cells reveals large-scale changes in the activated neuronal transcriptome after brief novel environment exposure, including induction of MAPK pathway genes. In addition, we observe a continuum of activation states, revealing a pseudotemporal pattern of activation from gene expression alone. In summary, snRNA-seq of activated neurons enables the examination of gene expression beyond IEGs, allowing for novel insights into neuronal activation patterns in vivo.
Efficient and Accurate Anomaly Identification Using Reduced Metric Space in Utility Clouds (2012)

The online detection of anomalies is a vital element of operations in utility clouds. Detection should function for different levels of abstraction including hardware and software, and for the various metrics used in cloud computing systems. Given ever-increasing cloud sizes coupled with the complexity of system components, continuous monitoring leads to the overwhelming volume of data collected by health monitoring tools. High metric dimensionality and existence of interacting metrics compromise the detection accuracy and lead to high detection complexity. In this paper, we present a metric selection framework and propose systematic approaches to effectively identify and select the most essential metrics for online anomaly detection in utility clouds. Specifically, a mutual information based approach selects metrics with the maximized mutual relevance and the minimized redundancy. Then metric space combination and separation are explored to reduce the metric dimensionality further. Experimental results on utility cloud scenarios demonstrate the viability and efficiency of this framework. The selected metrics contribute to a high efficiency and accuracy in anomaly detection.
High-Dose Granulocyte-Macrophage Colony-Stimulating Factor-Producing Vaccines Impair the Immune Response through the Recruitment of Myeloid Suppressor Cells (2004)

Tumor vaccines have shown promise in early clinical trials. Among them, tumor cells genetically engineered to secrete biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF) can generate a systemic antitumor immune response. Although the minimal required GM-CSF dose produced by modified tumor cells to achieve a measurable antitumor effect is well known, no data examined whether an upper therapeutic limit may exist for this vaccination strategy. Because recent data demonstrate an immunosuppressive effect of GM-CSF produced by growing tumors, we thus sought to determine whether high GM-CSF doses administered in a vaccine formulation could impair antitumor immunity. Using a vaccine strategy involving a GM-CSF-producing bystander cell line (B78H1-GM) admixed with autologous tumor, we assessed the impact of varying doses of GM-CSF while maintaining a constant antigen dose. Our results defined a threshold above which a GM-CSF-based vaccine not only lost its efficacy, but more importantly for its clinical implications resulted in substantial immunosuppression in vivo. Above this threshold, GM-CSF induced Gr1+/CD11b+ myeloid suppressor cells that substantially impaired antigen-specific T-cell responses and adversely affected antitumor immune responses in vivo. The dual effects of GM-CSF are mediated by the systemic and not local concentration of this cytokine. Myeloid suppressor cell-induced immunosuppression is mediated by nitric oxide production via inducible nitric oxide synthase (iNOS) because the specific iNOS inhibitor, l-NMMA, restored antigen-specific T-cell responsiveness in vitro. Taken together, our data demonstrated the negative impact of supra-therapeutic vaccine doses of GM-CSF and underscored the importance of identifying these critical variables in an effort to increase the therapeutic efficacy of tumor vaccines.
Molecular Cloning of a Novel Lipocalin-1 Interacting Human Cell Membrane Receptor Using Phage Display (2001)

Human lipocalin-1 (Lcn-1, also called tear lipocalin), a member of the lipocalin structural superfamily, is produced by a number of glands and tissues and is known to bind an unusually large array of hydrophobic ligands. Apart from its specific function in stabilizing the lipid film of human tear fluid, it is suggested to act as a physiological scavenger of potentially harmful lipophilic compounds, in general. To characterize proteins involved in the reception, detoxification, or degradation of these ligands, a cDNA phage-display library from human pituitary gland was constructed and screened for proteins interacting with Lcn-1. Using this method an Lcn-1 interacting phage was isolated that expressed a novel human protein. Molecular cloning and analysis of the entire cDNA indicated that it encodes a 55-kDa protein, lipocalin-1 interacting membrane receptor (LIMR), with nine putative transmembrane domains. The cell membrane location of this protein was confirmed by immunocytochemistry and Western blot analysis of membrane fractions of human NT2 cells. Independent biochemical investigations using a recombinant N-terminal fragment of LIMR also demonstrated a specific interaction with Lcn-1 in vitro. Based on these data, we suggest LIMR to be a receptor of Lcn-1 ligands. These findings constitute the first report of cloning of a lipocalin interacting, plasma membrane-located receptor, in general. In addition, a sequence comparison supports the biological relevance of this novel membrane protein, because genes with significant nucleotide sequence similarity are present in Takifugu rubripes, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, Bos taurus, and Sus scrofa. According to data derived from the human genome sequencing project, the LIMR-encoding gene has to be mapped on human chromosome 12, and its intron/exon organization could be established. The entire LIMR-encoding gene consists of about 13.7 kilobases in length and contains 16 introns with a length between 91 and 3438 base pairs.
ChemInform Abstract: 4‐[(8‐Alkyl‐8‐azabicyclo [3.2.1]octyl‐3‐yl)‐3‐arylanilino]‐N,N‐diethylbenzamides: High Affinity, Selective Ligands for the Delta Opioid Receptor Illustrate Factors Important to Antagonist Activity. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair of minor groove DNA interstrand crosslinks in mammalian cells produced by the pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136 (2005)

SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136 crosslinks form rapidly and persist compared to those produced by conventional crosslinking agents such as nitrogen mustard, melphalan or cisplatin which bind in the DNA major groove. A panel of Chinese hamster ovary (CHO) cells with defined defects in specific DNA repair pathways were exposed to the bi-functional agents SJG-136 and melphalan, and to their mono-functional analogues mmy-SJG and mono-functional melphalan. SJG-136 was >100 times more cytotoxic than melphalan, and the bi-functional agents were much more cytotoxic than their respective mono-functional analogues. Cellular sensitivity of both SJG-136 and melphalan was dependent on the XPF-ERCC1 heterodimer, and homologous recombination repair factors XRCC2 and XRCC3. The relative level of sensitivity of these repair mutant cell lines to SJG-136 was, however, significantly less than with major groove crosslinking agents. In contrast to melphalan, there was no clear correlation between sensitivity to SJG-136 and crosslink unhooking capacity measured using a modified comet assay. Furthermore, repair of SJG-136 crosslinks did not involve the formation of DNA double-strand breaks. SJG-136 cytotoxicity is likely to result from the poor recognition of DNA damage by repair proteins resulting in the slow repair of both mono-adducts and more importantly crosslinks in the minor groove.
Genetic analysis of epidermal growth factor action: assignment of human epidermal growth factor receptor gene to chromosome 7. (1980)

Purified murine epidermal growth factor (EGF) binds to mouse and human cells. Two mouse transformed cell lines of different origins, PG19 and B82, were found to lack EGF receptors (EGFR). The defect in each of these two cell lines seems to be identical because they fail to complement each other. Somatic cell hybrids between these EGFR-deficient mouse cells and human cells expressing EGFR were produced. Several of these hybrids bound labeled EGF. Detailed cytogenetic analysis of these cell hybrids, followed by correlation of EGFR expression with human chromosomes revealed that EGFR presence correlated with human chromosome 7. The results suggest that the structural gene or a gene necessary for expression of the human EGF receptor is located on human chromosome 7.
TIMP‐1 expression in human colorectal cancer is associated with TGF‐B1, LOXL2, INHBA1, TNF‐AIP6 and TIMP‐2 transcript profiles (2008)

The balance of activity between the endogenous enzyme inhibitors known as tissue inhibitors of metalloproteinases and their targets, the matrix metalloproteinases, in the extracellular matrix is thought to play an important role in tumour cell invasion. Supporting this notion, we have shown that colorectal cancer patients have increased plasma levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1), and that high plasma TIMP-1 levels are associated with short colorectal cancer patient survival. However, although TIMP-1 has been extensively studied in cancer, very little is known about how it is regulated. To further elucidate potential mechanisms of regulation of this protein, we did a number of experiments to look at associations between the transcript profile of TIMP-1 with known matrix metalloproteinases (MMPs) as well as with expression profiles of other genes differentially regulated in human colorectal cancer (CRC) and the other TIMPs 2-4, which have also been associated with the progression of colorectal cancer. Genome-wide expression profiling of 172 CRC and normal mucosa samples was used to identify transcript changes for the genes under investigation. We found that TIMP-1 was up-regulated in CRC samples compared with normal tissue, while TIMP-2 was down-regulated. Eight MMPs were up-regulated in CRC compared with normal tissue. Correlating up-regulated genes with the TIMP-1 transcript, we identified 13 that were also up-regulated in cancerous tissue. Among these were genes associated with the synthesis of extracellullar matrix, genes involved in the TGF-beta signalling pathway, and genes that are likely transcribed by the tumour cells. These insights add to the complex picture emerging about the regulation of TIMPs in colorectal cancer.
Antihypercholesterolemic Effect of Undigested Fraction of Soybean Protein in Young Female Volunteers. (1995)

The significant antihypercholesterolemic effect of the undigested high molecular fraction (HMF) of soybean protein is known in rats, but such an effect has not been shown in humans. The present two experiments were designed to elucidate it in humans. Subjects were female university students who had relatively high serum cholesterol levels for their age. In Experiment 1, subjects took 8% of their total energy from casein, soybean protein isolate (SPI), or HMF daily for 14 days. Five basic menus and snacks were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. The HMF group showed decreased low-density lipoprotein cholesterol (LDL-C) as compared to other groups. In Experiment 2, subjects took 4% of total energy from casein or HMF daily for a menstruation period. Five basic menus and snacks which contained two egg yolks (about 500 mg cholesterol) were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. A decrease in LDL-C and an increase in high-density lipoprotein cholesterol (HDL-C) were observed in the HMF group as compared to the casein group. Fecal acidic steroid excretion was greater in the HMF group than in the casein group (p < 0.05). The results confirmed that HMF increases fecal steroid excretion and reduces serum cholesterol levels in humans.
A One-Way Quantum Computer (2001)

We present a scheme of quantum computation that consists entirely of one-qubit measurements on a particular class of entangled states, the cluster states. The measurements are used to imprint a quantum logic circuit on the state, thereby destroying its entanglement at the same time. Cluster states are thus one-way quantum computers and the measurements form the program.
Fabrication and Manipulation of Ionotropic Hydrogels Cross-Linked by Paramagnetic Ions (2007)

This manuscript describes the fabrication and manipulation of millimeter-scale spheres fabricated from ionotropic hydrogels that are crosslinked with paramagnetic metal ions (e.g., Ho(3+)). These ionotropic hydrogels experience a force in a magnetic field gradient that correlates with the concentration of the paramagnetic cations crosslinking the polymer. In an externally applied magnetic field, the paramagnetic hydrogel spheres assemble into ordered arrays or confined geometrical structures in the regions of highest magnetic field. These spheres can be separated from heterogeneous mixtures of diamagnetic materials using a simple bar magnet. Two applications using these recoverable hydrogel spheres were demonstrated: i) When prepared with embedded indicator dyes bound to paper, the spheres were used as colorimetric sensors for pH. ii) When prepared with embedded activated carbon powder, they were used to remove organic materials from aqueous solutions.
Synthesis of 1,3-diazepin-2-one nucleosides as transition-state inhibitors of cytidine deaminase (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 1,3-diazepin-2-one nucleosides as transition-state inhibitors of cytidine deaminaseVictor E. Marquez, Paul S. Liu, James A. Kelley, John S. Driscoll, and John J. McCormackCite this: J. Med. Chem. 1980, 23, 7, 713–715Publication Date (Print):July 1, 1980Publication History Published online1 May 2002Published inissue 1 July 1980https://pubs.acs.org/doi/10.1021/jm00181a001https://doi.org/10.1021/jm00181a001research-articleACS PublicationsRequest reuse permissionsArticle Views200Altmetric-Citations31LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Differential Induction of Pyruvate Decarboxylase Subunits and Transcripts in Anoxic Rice Seedlings (1997)

In 2-d-old rice (Oryza sativa L.) seedlings subjected to anoxic stress, pyruvate decarboxylase (PDC) activity increased 9-fold during a 168-h period. A polyclonal PDC antiserum that recognized alpha- and beta-subunits was used to quantify PDC protein by an enzyme-linked immunosorbant assay and showed a 5.6-fold increase, suggesting that the anoxically induced enzyme has a higher specific activity than the PDC isoform present under normoxia. Immunoblot analysis showed that levels of both PDC subunits were induced by anoxia. Immunoprecipitation of proteins labeled in vivo during anoxic treatment demonstrated that the alpha-subunit was preferentially synthesized at the onset of anoxia. Two partial cDNAs, including a novel sequence, were cloned from a cDNA library made from seedlings subjected to anoxia for 6 h. Gene-specific probes used to quantify northern blots showed that two or three PDC mRNAs are differentially induced by anoxia in rice seedlings. Immunoprecipitation of in vitro translation products of mRNAs isolated a different times of anoxic treatment confirmed this findings Our results suggest that anoxic induction of rice PDC involves transcriptional and posttranscriptional regulation of gene expression as well as differences in enzyme characteristics.