gebhart/patrepeval huggingface dataset:
CDDO-Me Protects against Space Radiation-Induced Transformation of Human Colon Epithelial Cells (2010)

Radiation-induced carcinogenesis is a major concern both for astronauts on long-term space missions and for cancer patients being treated with therapeutic radiation. Exposure to radiation induces oxidative stress and chronic inflammation, which are critical initiators and promoters of carcinogenesis. Many studies have demonstrated that non-steroidal anti-inflammatory drugs and antioxidants can reduce the risk of radiation-induced cancer. In this study, we found that a synthetic triterpenoid, CDDO-Me (bardoxolone methyl), was able to protect human colon epithelial cells (HCECs) against radiation-induced transformation. HCECs that were immortalized by ectopic expression of hTERT and cdk4 and exhibit trisomy for chromosome 7 (a non-random chromosome change that occurs in 37% of premalignant colon adenomas) can be transformed experimentally with one combined exposure to 2 Gy of protons at 1 GeV/nucleon followed 24 h later by 50 cGy of (56)Fe ions at 1 GeV/nucleon. Transformed cells showed an increase in proliferation rate and in both anchorage-dependent and independent colony formation ability. A spectrum of chromosome aberrations was observed in transformed cells, with 40% showing loss of 17p (e.g. loss of one copy of p53). Pretreatment of cells with pharmacological doses of CDDO-Me, which has been shown to induce antioxidative as well as anti-inflammatory responses, prevented the heavy-ion-induced increase in proliferation rate and anchorage-dependent and independent colony formation efficiencies. Taken together, these results demonstrate that experimentally immortalized human colon epithelial cells with a non-random chromosome 7 trisomy are valuable premalignant cellular reagents that can be used to study radiation-induced colorectal carcinogenesis. The utility of premalignant HCECs to test novel compounds such as CDDO-Me that can be used to protect against radiation-induced neoplastic transformation is also demonstrated.
Cell Adhesion Mechanisms in Platelets (2008)

At sites of vascular injury, platelets come into contact with the subendothelial extracellular matrix which triggers their activation and the formation of a hemostatic plug. This process is crucial for normal hemostasis, but may also lead to pathological thrombus formation causing diseases such as myocardial infarction or stroke. The initial capture of flowing platelets is mediated by the interaction of the glycoprotein (GP) Ib-V-IX complex with von Willebrand factor (vWF) immobilized on exposed collagens. This interaction allows the binding of the collagen receptor GPVI to its ligand and to initiate cellular activation, a process that is reinforced by locally produced thrombin and soluble mediators released from platelets. These events lead to the shift of beta1 and beta3 integrins on the platelet surface from a low to a high affinity state, thereby enabling them to bind their ligands and to mediate firm adhesion, spreading, coagulant activity, and aggregation. This review summarizes the most important structural and functional properties of these adhesion receptors and briefly discusses their potential as targets for antithrombotic therapy.
Predicting residue solvent accessibility from protein sequence by considering the sequence environment (2000)

The solvent accessibility of each residue is predicted on the basis of the protein sequence. A set of 338 monomeric, non-homologous and high-resolution protein crystal structures is used as a learning set and a jackknife procedure is applied to each entry. The prediction is based on the comparison of the observed and the average values of the solvent-accessible area. It appears that the prediction accuracy is significantly improved by considering the residue types preceding and/or following the residue whose accessibility must be predicted. In contrast, the separate treatment of different secondary structural types does not improve the quality of the prediction. It is furthermore shown that the residue accessibility is much better predicted in small than in larger proteins. Such a discrepancy must be carefully considered in any algorithm for predicting residue accessibility.
Recombinant adeno-associated virus-mediated gene transfer into hematopoietic progenitor cells [published erratum appears in Blood 1995 Feb 1;85(3):862] (1994)

Recombinant adeno-associated viruses (rAAV) containing only the inverted terminal repeats (ITR) from the wild-type virus are capable of stable integration into the host cell genome, and expression of inserted genes in cultured cells. We have now defined the ability of rAAV to introduce genes into primary hematopoietic progenitors. A vector was constructed containing the coding sequences for beta- galactosidase (beta-gal), including a nuclear localization signal, under the control of a strong viral promotor. Infectious vector particles were prepared by cotransfection of the vector plasmid with a second plasmid that contained the coding sequences for AAV proteins into adenovirus-infected human embryonic kidney cells. These vector preparations transferred and expressed the beta-gal gene in human K562 erythroleukemia and Detroit 6 cells. Positive immunoselection yielded a population of enriched CD34+ cells that were transduced with the rAAV beta-gal vector. Nuclear localized enzyme expression was documented in 60% to 70% of infected cells. Progenitor-derived colonies that developed after 2 weeks in clonogenic cultures were shown to have viral- associated DNA at an estimated copy number of 1 to 2 per cell using a semiquantitative polymerase chain reaction (PCR) method. Integration of AAV into hematopoietic progenitors was documented using wild-type virus, as its genome may integrate at a preferred site on chromosome 19. Our data suggest that rAAV will transfer and express genes in primitive hematopoietic progenitors with high frequency, and support the development of this vector system for therapeutic gene transfer.
Detection and Treatment of Depressive Syndromes in a Rural Island Clinic (1999)

<i>Background:</i> Major depression is a serious and often persistent problem for 5 to 10 percent of patients in primary care. The detection and treatment of depression can be a particular challenge in rural settings. This study describes patterns of care for depression at a rural primary care clinic on an island off the coast of Washington State. <i>Methods:</i> For a period of 2 months, 226 primary care patients were evaluated for depression using a two-stage screening method. Structured chart abstraction was conducted for patients meeting criteria for major depression or dysthymia. <i>Results:</i> Ten percent of the study sample met <i>Diagnostic and Statistical Manual of Medical Disorders</i>, fourth edition, criteria for major depression, 4 percent met criteria for dysthymia, and 8 percent met criteria for major depression and dysthymia. Of the patients who had a diagnosis of major depression or dysthymia by the PRIME-MD, approximately 50 percent had their condition detected by their primary care provider, and approximately 50 percent received guideline level antidepressant treatment. Less than 40 percent of patients whose depression was treated with antidepressants made more than two visits during the 8 weeks after the initial prescription. <i>Conclusions:</i> These findings are consistent with those from other primary care settings and suggest that there are many opportunities for improving the quality of care for depressed patients in rural primary care settings.
Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. (1992)

Autotaxin (ATX) is a potent human motility-stimulating protein that has been identified in the conditioned medium from A2058 melanoma cells. This protein has been purified to homogeneity utilizing a strategy involving five column steps. Homogeneity of ATX was verified by two-dimensional gel electrophoresis. The molecular size of ATX is 125 kDa, and it has an isoelectric point of 7.7 +/- 0.2. Purified ATX was digested with cyanogen bromide and trypsin, and the resulting ATX peptides were purified by reverse-phase high performance liquid chromatography. Eleven peptides were subjected to amino acid sequence analysis, and 114 residues were identified. The partial amino acid sequences and the amino acid composition obtained for ATX show that it does not exhibit any significant homology to known growth factors or previously described motility factors. At picomolar concentrations, ATX stimulates both random and directed migration of human A2058 melanoma cells. Pretreatment of the melanoma cells with pertussis toxin abolishes the response to purified ATX, indicating that ATX stimulates motility through a receptor acting via a pertussis toxin-sensitive G protein.
SAG/ROC2/Rbx2/Hrt2 , a Component of SCF E3 Ubiquitin Ligase: Genomic Structure, a Splicing Variant, and Two Family Pseudogenes (2001)

We have recently cloned and characterized an evolutionarily conserved gene, Sensitive to Apoptosis Gene (SAG), which encodes a redox-sensitive antioxidant protein that protects cells from apoptosis induced by redox agents. The SAG protein was later found to be the second family member of ROC/Rbx/Hrt, a component of the Skp1-cullin-F box protein (SCF) E3 ubiquitin ligase, being required for yeast growth and capable of promoting cell growth during serum starvation. Here, we report the genomic structure of the SAG gene that consists of four exons and three introns. We also report the characterization of a SAG splicing variant (SAG-v), that contains an additional exon (exon 2; 264 bp) not present in wildtype SAG. The inclusion of exon 2 disrupts the SAG ORF and gives rise to a protein of 108 amino acids that contains the first 59 amino acids identical to SAG and a 49-amino acid novel sequence at the C terminus. The entire RING-finger domain of SAG was not translated because of several inframe stop codons within the exon 2. The SAG-v protein was expressed in multiple human tissues as well as cell lines, but at a much lower level than wildtype SAG. Unlike SAG, SAG-v was not able to rescue yeast cells from lethality in a ySAG knockout, nor did it bind to cullin-1 or have ligase activity, probably because of the lack of the RING-finger domain. Finally, we report the identification of two SAG family pseudogenes, SAGP1 and SAGP2, that share 36% or 47% sequence identity with ROC1/Rbx1/Hrt1 and 30% or 88% with SAG, respectively. Both genes are intronless with two inframe stop codons.
Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus (2010)

Percentages of IL-17 expressing T-cells correlate with disease activity. Further, these cells show increased expression of costimulatory markers such as CD134 and CD80. The presence of CD134+ T-cells in renal biopsies of lupus nephritis patients suggest that these cells migrate to the kidney and might contribute to inflammatory processes through IL-17 secretion.
Insulin Receptor Substrate and p55 Orthologous Adaptor Proteins Function in the Caenorhabditis elegans daf-2/Insulin-like Signaling Pathway (2002)

An insulin-like signaling pathway regulates development and lifespan in Caenorhabditis elegans. Genetic screens that identified many components of the C. elegans insulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for signaling by mammalian insulin/insulin-like growth factor I pathways. The C. elegans genome contains one homolog of each protein. The C. elegans versions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate and Drosophila counterparts. Genetic experiments show that ist-1 and aap-1 potentiate C. elegans insulin-like signaling, although they are not required for signaling in the pathway under most conditions. Worms lacking AAP-1 activity because of the mutation aap-1(m889) constitutively arrest development at the dauer larval stage when raised at high temperatures. aap-1 mutants also live longer than wild-type animals, a phenotype observed in other C. elegans mutants with defects in DAF-2 signaling. Interestingly, IST-1 appears to be required for signaling through a pathway that may act in parallel to AGE-1/PI3K.
The K-fgf/hst oncogene induces transformation through an autocrine mechanism that requires extracellular stimulation of the mitogenic pathway. (1991)

The K-fgf/hst oncogene encodes a secreted growth factor of the fibroblast growth factor (FGF) family. The ability of K-fgf-transformed cells to grow in soft agar and in serum-free medium is inhibited by anti-K-FGF neutralizing antibodies, consistent with an autocrine mechanism of transformation. The transformed properties of clones that express high levels of K-FGF are, however, only partially affected. To better define the autocrine mechanism of transformation by K-fgf and to determine whether receptor activation could occur intracellularly, we constructed two mutants of the K-fgf cDNA. Deletion of the sequences encoding the signal peptide suppressed K-fgf ability to induce foci in NIH 3T3 cells. A few morphologically transformed colonies were observed in cotransfection experiments, and they were found to express high levels of cytoplasmic K-FGF. However, their ability to grow in serum-free medium and in soft agar was inhibited by anti-K-FGF antibodies. Addition of a sequence encoding the KDEL endoplasmic reticulum and Golgi retention signal to the K-fgf cDNA led to accumulation of the growth factor in intracellular compartments. The ability of the KDEL mutant to induce foci in NIH 3T3 cells was much lower than that of the wild-type cDNA, and also in this case the transformed phenotype was reverted by anti-K-FGF antibodies. These and other findings indicate that the transformed phenotype of cells expressing a nonsecretory K-FGF is due to the extracellular activation of the receptor by the small amounts of growth factor that these cells still release. Thus, transformation by K-fgf appears to be due to an autocrine growth mechanisms that requires activation of the mitogenic pathway at the cell surface.
Collection of liquid propellants in zero gravity with electric fields (1965)

Covers advancements in spacecraft and tactical and strategic missile systems, including subsystem design and application, mission design and analysis, materials and structures, developments in space sciences, space processing and manufacturing, space operations, and applications of space technologies to other fields.
Phosphorothioate analogs of nucleotides (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphorothioate analogs of nucleotidesFritz EcksteinCite this: Acc. Chem. Res. 1979, 12, 6, 204–210Publication Date (Print):June 1, 1979Publication History Published online1 May 2002Published inissue 1 June 1979https://pubs.acs.org/doi/10.1021/ar50138a003https://doi.org/10.1021/ar50138a003research-articleACS PublicationsRequest reuse permissionsArticle Views461Altmetric-Citations101LEARN 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
The Chemistry of Isatoic Anhydride (1980)

A survey of the methods of preparation and reactions of isatoic anhydride is given. The reactions are classified into three major classes: substitution on nitrogen, substitution on the aromatic ring, and nucleophilic reactions. 1. Introduction 2. Synthesis of Isatoic Anhydrides 2.1. Ring Closure of Anthranilic Acids 2.2. Oxidation of Isatins 2.3. Reaction of Phthalic Anhydride with Azides 2.4. From Phthalimides 2.5. Oxidation of Phthalamic Acids 2.6. Oxidation of Indigo 2.7. Miscellaneous Preparations of Isatoic Anhydrides 2.8. Saturated Anhydrides 2.9. Hetero Anhydrides 2.10. Diisatoic Anhydrides 2.11. Polycyclic Anhydrides 3. Reactions of Isatoic Anhydrides 3.1. Substitution on Nitrogen 3.2. Substitution on the Aromatic Ring 3.3. Reaction with Water, Alcohols, and Thiols 3.4. Reaction with Amines 3.5. Reaction with Amides 3.6. Reaction with Ureas, Thioureas, and Thiopseudoureas 3.7. Reaction with Amidines and Related Compounds 3.8. Reaction with Carbanions 3.9. Miscellaneous Reactions 4. Addenda
A Stochastic Service Composition Model for Business Integration (2006)

One of the key challenges for contemporary enterprises is how to integrate business functions and IT systems within and across the enterprises. Among other approaches, the service-oriented architecture (SOA) has emerged as a prominent candidate to ensure the resulting business integration in a flexible, simple and technology-agnostic manor. A service is defined as a particular business unit of work or IT unit of system that is accessible by independent users and systems through a standardized interface. Therefore, business functions and IT systems are refactored to meet the requirements of SOA. As a result, business integration is modeled as a composition of atomic or composite business services and IT services. However, with their very nature, the results of using a business or IT service can be non-deterministic, i.e., one can't predict ahead of time the outcomes of invoking a business or IT service. For instance, a business service might provide a result short of the original expectation, which would require the use of another business service to compensate for the shortfalls. Consequently, the service composition model should also take the stochastic aspect into consideration. In this paper, we are going to propose a stochastic service composition model for business integration. This model extends the existing service composition model to take the stochastic aspect of the services into explicit consideration. We discuss the structure and potential usage of such a model. We then provide an example to illustrate how a stochastic service composition model can be utilized in a real-world setting for business integration.
Visual content layer for scalable object recognition in urban image databases (2009)

Rich online map interaction represents a useful tool to get multimedia information related to physical places. With this type of systems, users can automatically compute the optimal route for a trip or to look for entertainment places or hotels near their actual position. Standard maps are defined as a fusion of layers, where each one contains specific data such height, streets, or a particular business location. In this paper we propose the construction of a visual content layer which describes the visual appearance of geographic locations in a city. We captured, by means of a mobile mapping system, a huge set of georeferenced images (> 500 K) which cover the whole city of Barcelona. For each image, hundreds of region descriptions are computed off-line and described as a hash code. This allows an efficient and scalable way of accessing maps by visual content.
Organic Light Emitting Diodes with Reduced Spectral and Spacial Halfwidths (1998)

Organic light emitting diodes (OLEDs) with reduced spectral and spacial halfwidths for full-color imaging applications are investigated. The electroluminescence behaviour of the lanthanide complexes Eu(TTFA) 3 Phen and Tb(ACAC) 3 Phen having sharp emission lines in the red and green spectrum, respectively, is examined for different OLED structures. Device optimization criteria with respect to multilayer design and material choice for this type of device are given. A Fabry-Pérot microcavity OLED is investigated to narrow the spectral width of commonly used organic materials ( e.g. Alq 3 ) from 100 nm to only 13 nm, demonstrating blue and green emission. In addition, the forward emission at the resonance wavelength is 8 times higher in intensity accompanied by a reduced spacial halfwidth. The directivity is further improved using materials with inherent narrow spectral widths. A spacial full-width at half maximum (FWHM) of 12° is demonstrated if the europium complex Eu(TTFA) 3 Phen is embedded into a microcavity structure. Compared to a non-cavity device as a reference, the emission intensity in this direction is significantly enhanced by a factor of about 8.
Dual Inhibition of Tumor Energy Pathway by 2-Deoxyglucose and Metformin Is Effective against a Broad Spectrum of Preclinical Cancer Models (2011)

Tumor cell proliferation requires both growth signals and sufficient cellular bioenergetics. The AMP-activated protein kinase (AMPK) pathway seems dominant over the oncogenic signaling pathway suppressing cell proliferation. This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxyglucose (2DG) and AMPK agonists, AICAR and metformin. We evaluated the in vitro antitumor activity of 2DG, metformin or AICAR alone, and 2DG in combination either with metformin or AICAR. We examined in vivo efficacy using xenograft mouse models. 2DG alone was not sufficient to promote tumor cell death, reflecting the limited efficacy showed in clinical trials. A combined use of 2DG and AICAR also failed to induce cell death. However, 2DG and metformin led to significant cell death associated with decrease in cellular ATP, prolonged activation of AMPK, and sustained autophagy. Gene expression analysis and functional assays revealed that the selective AMPK agonist AICAR augments mitochondrial energy transduction (OXPHOS) whereas metformin compromises OXPHOS. Importantly, forced energy restoration with methyl pyruvate reversed the cell death induced by 2DG and metformin, suggesting a critical role of energetic deprivation in the underlying mechanism of cell death. The combination of 2DG and metformin inhibited tumor growth in mouse xenograft models. Deprivation of tumor bioenergetics by dual inhibition of energy pathways might be an effective novel therapeutic approach for a broad spectrum of human tumors.
Solution-Processed Naphthalene Diimide Derivatives as n-Type Semiconductor Materials (2008)

Two soluble 1,4,5,8-naphthalenetetracarboxylic diimide (NTCDI) derivatives with phenylmethyl and (trifluoro-methyl)benzyl groups (NTCDI-P and NTCDI-F, respectively) were synthesized and used as semiconductor layers in organic thin-film transistors (OTFTs) by a spin-coating process in air. These two synthesized materials were characterized by 1H NMR and UV−vis spectra as well as mass analysis. The morphology and crystallinity of spin-coated NTCDI-P and NTCDI-F films have been inspected using atomic force microscopy (AFM) and X-ray diffraction (XRD), respectively. The channel mobilities of these two NTCDI derivatives were calculated to be about 1.2 × 10-3 cm2 V-1 s-1 in air, which degraded slightly while stabilized for NTCDI-F OTFTs after exposure in air for 1 month.