gebhart/patrepeval huggingface dataset:
Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort (2012)

Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE) clinical features in a large lupus cohort. Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis. Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use.
Pilot Study of a Heptavalent Vaccine-Keyhole Limpet Hemocyanin Conjugate plus QS21 in Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer (2007)

This heptavalent-KLH conjugate plus QS21 vaccine safely induced antibody responses against five of seven antigens. Investigation in an adequately powered efficacy trial is warranted.
CD28 Costimulation Provided through a CD19-Specific Chimeric Antigen Receptor EnhancesIn vivoPersistence and Antitumor Efficacy of Adoptively Transferred T Cells (2006)

Chimeric antigen receptors (CAR) combine an antigen-binding domain with a CD3-zeta signaling motif to redirect T-cell specificity to clinically important targets. First-generation CAR, such as the CD19-specific CAR (designated CD19R), may fail to fully engage genetically modified T cells because activation is initiated by antigen-dependent signaling through chimeric CD3-zeta, independent of costimulation through accessory molecules. We show that enforced expression of the full-length costimulatory molecule CD28 in CD8(+)CD19R(+)CD28(-) T cells can restore fully competent antigen-dependent T-cell activation upon binding CD19(+) targets expressing CD80/CD86. Thus, to provide costimulation to T cells through a CD19-specific CAR, independent of binding to CD80/CD86, we developed a second-generation CAR (designated CD19RCD28), which includes a modified chimeric CD28 signaling domain fused to chimeric CD3-zeta. CD19R(+) and CD19RCD28(+) CD8(+) T cells specifically lyse CD19(+) tumor cells. However, the CD19RCD28(+) CD8(+) T cells proliferate in absence of exogenous recombinant human interleukin-2, produce interleukin-2, propagate, and up-regulate antiapoptotic Bcl-X(L) after stimulation by CD19(+) tumor cells. For the first time, we show in vivo that adoptively transferred CD19RCD28(+) T cells show an improved persistence and antitumor effect compared with CD19R(+) T cells. These data imply that modifications to the CAR can result in improved therapeutic potential of CD19-specific T cells expressing this second-generation CAR.
TLR Ligation Triggers Somatic Hypermutation in Transitional B Cells Inducing the Generation of IgM Memory B Cells (2010)

TLR9 activation by unmethylated CpG provides a homeostatic mechanism to maintain B cell memory in the absence of Ag. In this study, we demonstrate that CpG also triggers the generation of somatically mutated memory B cells from immature transitional B cells. In response to CpG, a fraction of transitional B cells proliferates and introduces somatic hypermutations in the H chain V regions. The nonproliferating pool of transitional B cells mostly maintains germline configurations. Mutations are VH specific: VH5 is the least mutated family, whereas VH1 and VH4/6 are the most mutated families. CpG stimulation also results in upregulation of VH5 transcripts in proliferating cells. Therefore, early recognition of bacterial DNA preferentially expands VH5-expressing B cells while inducing somatic hypermutations in other families. The mutation frequency, range, and type of substitutions observed in vitro are comparable to those found in memory B cells from the peripheral blood of Hyper IgM type 1 patients and the spleen of normal infants. The process triggered by TLRs may represent a first step leading to additional diversification of the germline repertoire and to the generation of memory B cells that will further refine their repertoire and specificity in the germinal centers.
Defects in heart and lung development in compound heterozygotes for two different targeted mutations at the N-myc locus (1993)

Two types of mutant allele, one leaky and one null, have been generated by gene targeting at the N-myc locus in embryonic stem cells and the phenotypes of mice homozygous for these mutations have been described. These mutations have shown that N-myc has a number of functions during development, including a role in branching morphogenesis in the lung, which manifests itself at birth in mice homozygous for the leaky allele, and roles in the development of the mesonephric tubules, the neuroepithelium, the sensory ganglia, the gut and the heart, which become evident at midgestation in embryos homozygous for the null allele. In an attempt to define roles for N-myc at other stages of development, we have combined the two types of N-myc mutant allele in a compound heterozygote that as a result contains approximately 15% of normal levels of N-Myc protein. Compound heterozygotes died during gestation at a time intermediate to the times of death of embryos homozygous for either mutation individually, and their death appeared to result from cardiac failure stemming from hypoplasia of the compact subepicardial layer of the myocardium. Investigation of the expression pattern of N-myc and various markers of differentiation in wild-type and compound heterozygote mutant hearts has suggested that N-myc may function in maintaining the proliferation and/or preventing the differentiation of compact layer myocytes. This study illustrates the importance of generating different mutations at a given locus to elucidate fully the function of a particular gene during development.
Quantitative comparison of molecular electrostatic potentials for structure‐activity studies (1991)

Abstract An approach for representing, efficiently calculating and comparing discrete three‐dimensional molecular electrostatic potentials using a quantitative similarity index (MEP‐SI) based on a Carbo‐type formalism is presented. A radial‐type (MACRA) grid representation is described that provides more efficient storage of MEP information than a cubic grid of similar range, appropriate emphasis, and a convenient means for restricting the comparison of MEP functions to a local molecule region. The MACRA based MEP‐SI formalism was used to evaluate the suitability of a variety of approximate methods for efficiently calculating the MEP for use in MEP‐SI comparison of dissimilar molecules. The Mulliken charge method was found inadequate, while the method of potential‐derived charges (PDCs), with additional charges for lone electron pairs included on sulfur, provided an efficient and sufficiently accurate representation of the MEP for this purpose. Convergence of the MEP‐SI with respect to MACRA grid extent and mesh size was demonstrated; the effect of MEP error and different grid point emphasis in the MACRA versus the cubic grid results was investigated, and MEP‐SI results were compared for different forms of the SI equation. The methodology proposed in this study provides an efficient and practical means for comparing MEP functions for two molecules and gives discriminating results for a sample series of molecular analogues consistent with expectations.
Raman Spectroscopy and Related Techniques in Biomedicine (2010)

In this review we describe label-free optical spectroscopy techniques which are able to non-invasively measure the (bio)chemistry in biological systems. Raman spectroscopy uses visible or near-infrared light to measure a spectrum of vibrational bonds in seconds. Coherent anti-Stokes Raman (CARS) microscopy and stimulated Raman loss (SRL) microscopy are orders of magnitude more efficient than Raman spectroscopy, and are able to acquire high quality chemically-specific images in seconds. We discuss the benefits and limitations of all techniques, with particular emphasis on applications in biomedicine--both in vivo (using fiber endoscopes) and in vitro (in optical microscopes).
Tumor-associated macrophages (2010)

Mononuclear phagocytes are versatile cells that can express different functional programs in response to microenvironmental signals. Fully polarized Ml and M2 macrophages are the extremes of a continuum of functional states. Macrophages that infiltrate tumor tissues are driven by tumor-derived cytokines to acquire a polarized M2 phenotype. These functionally polarized cells play a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression. It is notable that tumor-associated macrophages promote the proliferation, invasiveness and metastasis of tumor cells ,and participate in neovas-cularization, and immunosuppression of the tumor.

Key words: 
Macrophage; Tumor associated macrophages; Tumor; Angiogenesis
How to make ad-hoc polymorphism less ad hoc (1989)

This paper presents type classes, a new approach to ad-hoc polymorphism. Type classes permit overloading of arithmetic operators such as multiplication, and generalise the “eqtype variables” of Standard ML. Type classes extend the Hindley/Milner polymorphic type system, and provide a new approach to issues that arise in object-oriented programming, bounded type quantification, and abstract data types. This paper provides an informal introduction to type classes, and defines them formally by means of type inference rules.
Possible role of cyclic AMP phosphodiesterases in the actions of ibudilast on eosinophil thromboxane generation and airways smooth muscle tone (1994)

1. The possible role of cyclic AMP phosphodiesterase (PDE) in the inhibitory actions of ibudilast on tracheal smooth muscle contractility and eosinophil thromboxane generation was investigated. 2. Ibudilast was a non-selective inhibitor of partially purified cyclic nucleotide PDE isoenzymes from pig aorta and bovine tracheal smooth muscle, exhibiting only moderate potency against bovine tracheal PDE IV (IC50 = 12 +/- 4 microM, n = 3). Similar or slightly lower potencies were displayed against PDEs I, II, III and V. In contrast, rolipram exhibited selectivity for PDE IV (3 +/- 0.5 microM, n = 3). 3. Ibudilast (IC50 = 0.87 +/- 0.37 microM, n = 3), like rolipram (IC50 = 0.20 +/- 0.04 microM, n = 3), was a more potent inhibitor of membrane-bound PDE IV from guinea-pig eosinophils than of partially purified PDE IV from bovine tracheal smooth muscle. The potency of ibudilast increased when the eosinophil enzyme was solubilised with deoxycholate and NaCl (IC50 = 0.11 +/- 0.05 microM, n = 3) or exposed to vanadate/glutathione complex (V/GSH) (IC50 = 0.11 +/- 0.02 microM, n = 3). The potency of rolipram was also increased by solubilization (IC50 = 0.012 +/- 0.003, n = 3) or V/GSH (IC50 = 0.012 +/- 0.003, n = 3). 4. In intact eosinophils, ibudilast (0.032 microM-20 microM) potentiated isoprenaline-induced cyclic AMP accumulation in a concentration-dependent manner, being approximately 20 fold less potent than rolipram. Little or no effect on basal cyclic AMP levels was observed with either compound. The cyclicAMP-dependent protein kinase activity ratio was significantly increased following incubation of eosinophils with either ibudilast (20 MicroM) or rolipram (20 MicroM) in the absence or presence of isoprenaline.5. Leukotriene B4 (300 nM)-induced thromboxane generation from guinea-pig eosinophils was inhibited by ibudilast (IC50 = 11.3 +/- 3.7 MicroM, n = 5) and rolipram (IC50 = 0.280 +/- 0.067 MicroM, n = 5) in a concentration-dependent manner.6. Ibudilast (10 nM-1 MicroM), whilst generally less potent than rolipram (1 nM- 1 MicroM), produced concentration-dependent relaxation of spasmogen (methacholine, histamine, LTD4)-induced tone in the guinea pig isolated tracheal strip. Ibudilast was less potent in reversing the methacholine (IC50 = 1.95 +/- 0.40 JM,n =6)-induced contraction than those of histamine (IC50 = 0.18 +/- 0.70 MicroM, n =6) or leukotriene D4(LTD4, IC50 = 0.12 +/- 0.05 MicroM, n = 6). Rolipram also exhibited a similar pattern of activity, although the difference in potency against methacholine (IC50 = 0.1 +/- 0.01 MicroM, n = 6) compared with the other two spasmogens, histamine (IC50 = 0.034 +/- 0.017 MicroM, n = 7) and LTD4 (IC50 = 0.026 +/- 0.008 MicroM, n = 7), was not as great.7. These results demonstrate that ibudilast, like rolipram, has several biological actions on the eosinophil and airways smooth muscle which may be attributed to inhibition of cyclic AMP PDE. These actions may account, at least in part, for the recently reported anti-asthma effects of ibudilast.
Designed strategy to fabricate a patterned V2O5nanobelt array as a superior electrode for Li-ion batteries (2010)

A V2O5 nanobelt array has been designed and prepared on a conductive substrate for the first time. The synthesis strategy is based on the hydrogen bonding action between the functionalized surface of a Ti substrate and the earlier-formed V2O5·xH2O nanoseeds, and 1-dimensional (1-D) growth property of V2O5·xH2O. The as-prepared V2O5 nanobelt array exhibits a greatly enhanced performance in Li-ion batteries as the cathode and anode; meanwhile, the enhancement mechanism is presented, which is not only important to design functional materials in Li-ion batteries, but also extendable to other systems' design and fabrication.
Phase II clinical evaluation of doxifluridine. (1986)

Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.
The Effect of Oral Therapy with Cobaltous Chloride on the Blood of Patients Suffering with Chronic Suppurative Infection (1949)

DURING a study of prolonged suppurative infection in 91 young men, we observed reticulocytosis, which was followed by increases in hematocrit and hemoglobin values, in the blood of patients being given cobaltous chloride by mouth.1 These findings were not completely unexpected since it has long been known that cobalt is a hematopoietic agent effective in deficient2 and healthy animals.3 Therapy with cobalt apparently stimulates red-cell production in children,4 as well as in adults,5 and also protects animals from developing anemia when sterile suppuration is induced experimentally.6 As far as we are aware cobalt has not been employed in this country . . .
Selective reductions of 3-substituted hydantoins to 4-hydroxy-2-imidazolidinones and vicinal diamines (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective reductions of 3-substituted hydantoins to 4-hydroxy-2-imidazolidinones and vicinal diaminesSergio Cortes and Harold KohnCite this: J. Org. Chem. 1983, 48, 13, 2246–2254Publication Date (Print):July 1, 1983Publication History Published online1 May 2002Published inissue 1 July 1983https://pubs.acs.org/doi/10.1021/jo00161a021https://doi.org/10.1021/jo00161a021research-articleACS PublicationsRequest reuse permissionsArticle Views1453Altmetric-Citations39LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Quantitation of human immunodeficiency virus type 1 infection kinetics (1993)

Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/ti, where n is the number of infectious virions produced by one cell (about 10(2)) and ti is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle.
Rapid and Scalable Plant-based Production of a Cholera Toxin B Subunit Variant to Aid in Mass Vaccination against Cholera Outbreaks (2013)

Taken together, these results demonstrated that pCTB has robust producibility in Nicotiana plants and retains most, if not all, of major biological activities of the original protein. This rapid and easily scalable system may enable the implementation of pCTB to mass vaccination against outbreaks, thereby providing better protection of high-risk populations in developing countries.
Red Phosphorescent Iridium Complex Containing Carbazole‐Functionalized β‐Diketonate for Highly Efficient Nondoped Organic Light‐Emitting Diodes (2006)

Abstract A novel red phosphorescent iridium complex containing a carbazole‐functionalized β‐diketonate, Ir(DBQ) 2 (CBDK) (bis(dibenzo[f,h]quinoxalinato‐ N ,C 2 ) iridium (1‐(carbazol‐9‐yl)‐5,5‐dimethylhexane‐2,4‐diketonate)) is designed, synthesized, and characterized. The electrophosphorescence properties of a nondoped device using the title complex as an emitter with a device configuration of indium tin oxide (ITO)/ N , N ′‐diphenyl‐ N , N ′‐bis(1‐naphthyl)‐1,1′‐diphenyl‐4,4′‐diamine (NPB; 20 nm)/iridium complex (20 nm)/2,9‐dimethyl‐4,7‐diphenyl‐1,10‐phenanthroline (BCP; 5 nm)/tris(8‐hydroxyquinoline) (AlQ; 30 nm)/Mg 0.9 Ag 0.1 (200 nm)/Ag (80 nm) are examined. The results show that the nondoped device achieves a maximum lumen efficiency as high as 3.49 lm W –1 . To understand this excellent result observed, two reference complexes Ir(DBQ) 2 (acac), where acac is the acetyl acetonate anion, and Ir(DBQ) 2 (FBDK), [bis(dibenzo[f,h]quinoxalinato‐ N ,C 2 ) iridium (1‐(9‐methyl‐fluoren‐9‐yl)‐6,6‐dimethylheptane‐3,5‐diketonate)], have also been synthesized, and as emitters they were examined under the same device configuration. The maximum lumen efficiency of the former compound is found to be 0.26 lm W –1 while that for the latter is 0.37 lm W –1 , suggesting that the excellent performance of Ir(DBQ) 2 (CBDK) can be attributed mainly to an improved hole‐transporting property that benefits the exciton transport. In addition, a bulky diketonate group separates the emitter centers from each other, which is also important for organic light‐emitting diodes.
Interleukin‐8, a chemotactic and inflammatory cytokine (1992)

Interleukin-8 (IL-8) belongs to a family of small, structurally related cytokines similar to platelet factor 4. It is produced by phagocytes and mesenchymal cells exposed to inflammatory stimuli (e.g., interleukin-1 or tumor necrosis factor) and activates neutrophils inducing chemotaxis, exocytosis and the respiratory burst. In vivo, IL-8 elicits a massive neutrophil accumulation at the site of injection. Five neutrophil-activating cytokines similar to IL-8 in structure and function have been identified recently. IL-8 and the related cytokines are produced in several tissues upon infection, inflammation, ischemia, trauma etc., and are thought to be the main cause of local neutrophil accumulation.