gebhart/patrepeval huggingface dataset:
Mechanism of acute anthracycline cardiotoxicity in isolated rat hearts: carminomycin versus daunomycin. (1984)

Cardiotoxicity limits the use of anthracyclines which are potent anticancer agents. In the isolated rat heart, we investigated the mechanism of acute anthracycline cardiotoxicity and compared a new anthracycline, carminomycin, with daunomycin which is in established use. Daunomycin 1.75 X 10(-5) M produced a fall in cardiac output (36 +/- 2 versus 58 +/- 1 ml/min; p less than 0.01), left ventricular power production (9 +/- 0.7 versus 16 +/- 0.3 mJ/sec/g; p less than 0.01), and efficiency of heart work (3.3 +/- 0.2 versus 6.3 +/- 0.2 mJ/sec/ml O2; p less than 0.01; mean +/- S.E. 40 min after daunomycin). Carminomycin (1.75 X 10(-5) M) produced a greater fall in cardiac output than equimolar daunomycin (26 +/- 2 versus 36 +/- 2 ml/min; p less than 0.01). Daunomycin did not reduce coronary flow rate, heart rate, or oxygen consumption. From the preceding data, we inferred that, since afterload and preload were constant in this model, heart failure was due to a depressed inotropic state. Procedures that increased cytosolic calcium relieved heart failure namely, pretreatment with digoxin (62.4 micrograms), isoproterenol (10(-6) M), and increased perfusate Ca2+ (5 mM versus 2.5 mM) all prevented carminomycin-induced fall in cardiac output (41 +/- 1, 47 +/- 5, and 52 +/- 1, respectively, versus 26 +/- 2 ml/min; p less than 0.01). Acute anthracycline contractile failure was also associated with a fall in high-energy phosphate compounds which could also have contributed to the decreased inotropic state. We conclude that carminomycin is more cardiotoxic than daunomycin in equimolar concentrations and that a lowered cytosolic calcium and decreased energy stores might cause the contractile failure. The cytosolic calcium and high-energy phosphate compounds were lowered by separate mechanisms.
A new model for an etiology of rheumatoid arthritis: Smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullination (2005)

We identified an environmental factor, smoking, that in the context of HLA-DR SE genes may trigger RA-specific immune reactions to citrullinated proteins. These data thus suggest an etiology involving a specific genotype, an environmental provocation, and the induction of specific autoimmunity, all restricted to a distinct subset of RA.
Tissue-specific mRNA expression profiling in grape berry tissues (2007)

These results revealed novel insights into the tissue-specific expression mRNA expression patterns of an extensive repertoire of genes expressed in berry tissues. This work also establishes an extensive catalogue of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern tissue-specific expression patterns associated with tissue differentiation within berries. These results also confirmed that water-deficit stress has a profound effect on mRNA expression patterns particularly associated with the biosynthesis of aroma and color metabolites within skin and pulp tissues that ultimately impact wine quality.
Downregulation of Macrophage Activation by PPARγ Suggests a Role for Conjugated Linoleic Acid in Prevention of Alzheimer's Disease and Atherosclerosis (1998)

There is evidence that monocytes/macrophages, especially when activated, express the peroxisome proliferator-activated receptor γ(PPARγ) transcription factor and that activation of PPARγ with appropriate ligands downregulates induced macrophage production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Another report indicates that dietary conjugated linoleic acids (CLA) have a thiazolidinedione-like antidiabetic effect in Zucker fatty rats, associated with activation of PPARγ in adipocytes. This raises the prospect that CLA might exert antiinflammatory effects by suppressing macrophage cytokine production via PPARγ. Omega-3-rich fish oils likewise can downregulate production of IL-1 and TNF by macrophages, possibly because they inhibit autocrine positive feedback by thromboxane A2. Therefore, supplemental CLA (fish oil) may be protective with respect to pathologies in which IL-1 and TNF play key etiological roles. Such pathologies may include atherogenesis and Alzheimer's disease. Antiatherogenic effects of both CLA and fish oil have been observed in animal models. With regard to Alzheimer's disease, the ability of dietary oils to reach the brain implies that CLA/fish oil may have greater clinical utility than drugs that have limited blood-brain barrier penetrance. Available epidemiological data are consistent with the possibility that frequent fish ingestion may decrease the risk of Alzheimer's disease.
Microsoft Data Warehousing: Building Distributed Decision Support Systems (1999)

THE 5 ENVIRONMENTS Decision Support Architectures The Source Environment The Storage Environment The Desktop Environment The Data Warehouse Life Cycle BUILDING A MICROSOFT-BASED DECISION SUPPORT SYSTEM Design Process and Tools Development Implementation Operations and Management Analytical Applications Bibliography Index.
Cystic Fibrosis Gene and Protein Expression during Fetal Lung Development (1993)

The cystic fibrosis transmembrane conductance regulator (CFTR) transports Cl- in the apical membrane of secretory epithelial cells. Normal lung development is critically dependent on active Cl- secretion by developing airway epithelia. In this study, the polymerase chain reaction (PCR) was used to detect CFTR mRNA expression in rabbit lung at different stages of development. Using nested amplification in exons 7 and 11, a 494-bp fragment was isolated from cDNA prepared from lungs obtained at gestational days 22 (pseudoglandular) and 29 (terminal sac). Nucleotide sequencing verified the identification of rabbit CFTR sequences. At day 22 of gestation, CFTR was detected in fetal liver, kidney, heart, intestine, and brain. CFTR could not be amplified from adult rabbit brain. CFTR protein was detected using a polyclonal antibody raised in chickens against a synthetic peptide from the R domain conjugated to thyroglobulin. Rabbit CFTR migrated as a 165-kD protein on 5% sodium dodecyl sulfate polyacrylamide gels when detected either by chicken anti-R IgG or a previously characterized rabbit anti-R antibody. In frozen sections of fetal rabbit lung at day 22 of gestation, CFTR was localized to the membrane regions of primitive tubular epithelial cells and absent from surrounding connective tissue. At day 29, CFTR was concentrated in the apical region of bronchiolar epithelial cells and absent from alveoli and vessels. These results suggest that CFTR gene expression begins very early in lung development and, with differentiation of the airways, becomes confined to differentiated bronchiolar epithelium, the presumed site for cAMP-mediated Cl- secretion.
Sequence-specific interaction with the viral AL1 protein identifies a geminivirus DNA replication origin. (1992)

The bipartite geminiviruses such as tomato golden mosaic virus (TGMV) and squash leaf curl virus (SqLCV) have two single-stranded circular genomic DNAs, the A and B components, thought to be replicated from double-stranded circular DNA intermediates. Although it has been presumed that the origin sequences for viral replication are located in the highly conserved 200-nucleotide common region (CR) present in both genomic components and that the viral-encoded AL1 protein interacts with these sequences to effect replication, there has been no evidence that this is in fact so. We have investigated these questions, demonstrating selectivity and sequence specificity in this protein-DNA interaction. Simple component switching between the DNAs of TGMV and SqLCV and analysis of replication in leaf discs showed that whereas the A components of both TGMV and SqLCV promote their own replication and that of their cognate B component, neither replicates the noncognate B component. Furthermore, using an in vivo functional replication assay, we found that cloned viral CR sequences function as a replication origin and direct the replication of nonviral sequences in the presence of AL1, with both circular single-stranded and double-stranded DNA being synthesized. Finally, by the creation of chimeric viral CRs and specific subfragments of the viral CR, we demonstrated sequence-specific recognition of the replication origin by the AL1 protein, thereby localizing the origin to an approximately 90-nucleotide segment in the AL1 proximal side of the CR that includes the conserved geminiviral stem-loop structure and approximately 60 nucleotides of 5' upstream sequence. By deletional analysis, we further demonstrated that the conserved stem-loop structure is essential for replication. These studies identify the functional viral origin of replication within the CR, demonstrating that sequence-specific recognition of this origin by the AL1 protein is required for replication.
Sentient Ascend: AI-Based Massively Multivariate Conversion Rate Optimization (2018)

Conversion rate optimization (CRO) means designing an e-commerce web interface so that as many users as possible take a desired action such as registering for an account, requesting a contact, or making a purchase. Such design is usually done by hand, evaluating one change at a time through A/B testing, or evaluating all combinations of two or three variables through multivariate testing. Traditional CRO is thus limited to a small fraction of the design space only. This paper describes Sentient Ascend, an automatic CRO system that uses evolutionary search to discover effective web interfaces given a human-designed search space. Design candidates are evaluated in parallel on line with real users, making it possible to discover and utilize interactions between the design elements that are difficult to identify otherwise. A commercial product since September 2016, Ascend has been applied to numerous web interfaces across industries and search space sizes, with up to four-fold improvements over human design. Ascend can therefore be seen as massively multivariate CRO made possible by AI.
A Semi-Parallel Successive-Cancellation Decoder for Polar Codes (2012)

Polar codes are a recently discovered family of capacity-achieving codes that are seen as a major breakthrough in coding theory. Motivated by the recent rapid progress in the theory of polar codes, we propose a semi-parallel architecture for the implementation of successive cancellation decoding. We take advantage of the recursive structure of polar codes to make efficient use of processing resources. The derived architecture has a very low processing complexity while the memory complexity remains similar to that of previous architectures. This drastic reduction in processing complexity allows very large polar code decoders to be implemented in hardware. An <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$N=2^{17}$</tex> </formula> polar code successive cancellation decoder is implemented in an FPGA. We also report synthesis results for ASIC.
Glucose-induced insulin secretion from purified beta-cells. A role for modulation of Ca2+ influx by cAMP- and protein kinase C-dependent signal transduction pathways. (1993)

The effects of activation of cAMP- and protein kinase C-dependent signal transduction pathways were investigated on intracellular Ca2+ concentration ([Ca2+]i), cAMP content and insulin secretion from beta-cells purified by fluorescence-activated cell sorting from normal rat islets. The secretion of insulin from suspensions of purified beta-cells was dependent on glucose concentration and hormonal signals, including cAMP and activators of protein kinase C. Microfluorimetric measurement of [Ca2+]i with the fluorescent Ca2+ indicator fura-2 indicated that beta-cells differed immensely in their individual responsiveness to glucose stimulation. An increase in [Ca2+]i occurred in approximately 70% of beta-cells, whereas approximately 30% of beta-cells were nonresponsive to a glucose stimulus. Elevation of cAMP levels by theophylline or glucagon transformed nonresponsive beta-cells into cells which displayed marked increases in [Ca2+]i, and beta-cells which exhibited glucose-induced changes in [Ca2+]i showed further increases in [Ca2+]i and in the amplitude of Ca2+ oscillations. Carbachol and 12-O-tetradecanoylphorbol-13-acetate, activators of protein kinase C, did not induce any alterations in intracellular cAMP levels; nonetheless, these agents increased both the number of beta-cells which exhibited glucose-induced changes in [Ca2+]i and the amplitude of oscillations. The ability of cAMP or activators of protein kinase C to increase [Ca2+]i in single beta-cells was directly correlated with the ability of beta-cell suspensions to secrete insulin in response to a glucose stimulus. These results suggest that both cAMP- and protein kinase C-dependent pathways may regulate Ca2+ entry into beta-cells, possibly via voltage-dependent Ca2+ channels. Thus, this may represent a common mechanism whereby these different signal transduction pathways potentiate glucose-induced insulin secretion from beta-cells.
Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc (2004)

Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio) in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.
Structure-activity relation of chloramphenicols (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure-activity relation of chloramphenicolsCorwin Hansch, Kenneth Nakamoto, Michael Gorin, Peter Denisevich, Edward R. Garrett, S. M. Heman-Ackah, and C. H. WonCite this: J. Med. Chem. 1973, 16, 8, 917–922Publication Date (Print):August 1, 1973Publication History Published online1 May 2002Published inissue 1 August 1973https://pubs.acs.org/doi/10.1021/jm00266a011https://doi.org/10.1021/jm00266a011research-articleACS PublicationsRequest reuse permissionsArticle Views314Altmetric-Citations37LEARN 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
Development of a Trispecific Antibody Designed to Simultaneously and Efficiently Target Three Different Antigens on Tumor Cells (2015)

Targeting Eph (erythropoietin producing hepatoma) receptors with monoclonal antibodies is being explored as therapy for several types of cancer. To test whether simultaneous targeting of EphA2, EphA4, and EphB4 would be an effective approach to cancer therapy, we generated a recombinant trispecific antibody using the variable domain genes of anti-EphA2, anti-EphA4, and anti-EphB4 monoclonal antibodies. A multidisciplinary approach combining biochemical, biophysical, and cellular-based assays was used to characterize the trispecific antibody in vitro and in vivo. Here we demonstrate that the trispecific antibody is expressed at high levels by mammalian cells, monodispersed in solution, thermostable, capable of simultaneously binding the three receptors, and able to activate the three targets effectively as evidenced by receptor internalization and degradation both in vitro and in vivo. Furthermore, pharmacokinetic analysis using tumor-bearing nude mice showed that the trispecific antibody remains in the circulation similarly to its respective parental antibodies. These results indicate that simultaneous blockade of EphA2, EphA4, and EphB4 could be an attractive approach to cancer therapy.
Differential Regulation of the Cell Wall Integrity Mitogen-Activated Protein Kinase Pathway in Budding Yeast by the Protein Tyrosine Phosphatases Ptp2 and Ptp3 (1999)

Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity and protein tyrosine phosphatases (PTPs) in yeasts. In Saccharomyces cerevisiae, two PTPs, Ptp2 and Ptp3, inactivate the MAPKs, Hog1 and Fus3, with different specificities. To further examine the functions and substrate specificities of Ptp2 and Ptp3, we tested whether they could inactivate a third MAPK, Mpk1, in the cell wall integrity pathway. In vivo and in vitro evidence indicates that both PTPs inactivate Mpk1, but Ptp2 is the more effective negative regulator. Multicopy expression of PTP2, but not PTP3, suppressed growth defects due to the MEK kinase mutation, BCK1-20, and the MEK mutation, MKK1-386, that hyperactivate this pathway. In addition, deletion of PTP2, but not PTP3, exacerbated growth defects due to MKK1-386. Other evidence supported a role for Ptp3 in this pathway. Expression of MKK1-386 was lethal in the ptp2Delta ptp3Delta strain but not in either single PTP deletion strain. In addition, the ptp2Delta ptp3Delta strain showed higher levels of heat stress-induced Mpk1-phosphotyrosine than the wild-type strain or strains lacking either PTP. The PTPs also showed differences in vitro. Ptp2 was more efficient than Ptp3 at binding and dephosphorylating Mpk1. Another factor that may contribute to the greater effectiveness of Ptp2 is its subcellular localization. Ptp2 is predominantly nuclear whereas Ptp3 is cytoplasmic, suggesting that active Mpk1 is present in the nucleus. Last, PTP2 but not PTP3 transcript increased in response to heat shock in a Mpk1-dependent manner, suggesting that Ptp2 acts in a negative feedback loop to inactivate Mpk1.
The use of fetal tissue for therapeutic applications (1993)

In recent years, dramatic progress has been made through research using dead human fetal tissue. Cellular transplantation is an attractive alternative to organ grafting when only a discrete function of the organ is impaired. Early fetal donor cells have an advantage because they engraft readily and do not cause graft-versus-host disease. Similarly, the fetus is an ideal recipient of allogenic fetal cells as it is incapable of rejecting them early in gestation. Recent research advances have led to its use in endocrine, neurologic and immune system disorders as well as in hematologic and hepatic deficiencies. Concurrently, this research has led to controversy over the ethics of using human fetal tissue, particularly tissue from induced abortions. Although legalized abortion remains a hotly debated controversial issue in the USA and some other countries, a consensus has been forming, in the scientific community, on the ethical use of fetal tissue in research and clinical transplantation. This review presents the theoretical background and recent research and clinical advances in fetal tissue transplantation, in the light of the current debate on its ethical and moral implications.
Eliciting T Cell Immunity Against Poorly Immunogenic Tumors by Immunization with Dendritic Cell-Tumor Fusion Vaccines (1998)

Dendritic cells (DCs) are the most effective APCs and are being studied as natural adjuvants or Ag delivery vehicles to elicit T cell-mediated antitumor immunity. This study examined whether inoculation of DCs fused with poorly immunogenic tumor cells elicited tumor-reactive T cells for adoptive immunotherapy. DCs derived from bone marrow of C57BL/6 (B6) mice were fused with syngeneic B16 melanoma or RMA-S lymphoma cells by polyethylene glycol. The B16/DC and RMA-S/DC fusion hybrids expressed MHC class I, class II Ags, costimulatory molecules, as well as DC-specific and tumor-derived surface markers. The tumor/DC hybrids were capable of processing and presenting tumor-derived Ags, and immunization of B6 mice with irradiated B16/DC or RMA-S/DC vaccine elicited tumor-specific CTL activities. Vaccination of B6 mice with irradiated B16/DC fusion preparations induced partial host protective immunity against B16 tumor challenge. Reduced tumor incidence and prolonged survival time were observed. Adoptive transfer of T cells derived from B16/DC vaccine-primed lymph nodes into B16 tumor-bearing mice greatly reduced the number of established pulmonary metastases with or without in vivo administration of IL-2. Moreover, adoptive transfer of RMA-S/DC vaccine-primed, cultured lymph node T cells eradicated disseminated FBL-3 tumor. The results demonstrate that tumor/DC fusion products are effective cellular vaccines for eliciting T cell-mediated antitumor immunity.
Transmissive properties of Ag/MgF2 photonic band gaps (1998)

We present results of transmittance measurements on periodic layers of Ag/MgF2 at optical and microwave frequencies. These one-dimensional, photonic band gap materials exhibit transparency bands at optical frequencies and a huge stop band that extends throughout the near-IR to microwave frequencies and beyond. A unique feature of these metal/dielectric photonic band gap (MD–PBG) materials is that the overall transmittance in the pass band may increase as more periods are deposited. The center frequency, width, and sharpness of the pass bands are adjustable and generally depend on the thickness of the layers and the number of Ag/MgF2 periods. These simple periodic structures have applications as sensor and eye protection devices, heat reflecting windows, ultraviolet blocking films, and transparent electrodes for light emitting diodes and liquid crystal displays.