gebhart/patrepeval huggingface dataset:
Polyelectrolyte multilayers fabricated from ‘charge-shifting’ anionic polymers: a new approach to controlled film disruption and the release of cationic agents from surfaces (2008)

We report an approach to the design of 'charge-shifting' anionic polymers that provides control over the disruption of ultrathin polyelectrolyte multilayers in aqueous media. We demonstrate that the addition of citraconic anhydride to poly(allylamine) yields an anionic, carboxylate-functionalized polymer (polymer 2) that can be converted readily back to cationic poly(allylamine) in acidic environments. The incorporation of polymer 2 into polyelectrolyte multilayers thus provides an approach to the fabrication of films that are stable at neutral pH but that erode over a period of several days in acidic media (e.g., pH ∼5). Experiments using a structural analog of polymer 2 with carboxylate side chains that do not hydrolyze readily provided support for the view that the disruption of these films occurred as a result of polymer side chain hydrolysis and a resulting change in the net charge of the polymers. Because this approach is based upon the use of anionic polymers to induce film instability, it provides a platform for the design of multilayers that can be used to provide control over the release of cationic film components. As proof of concept, we demonstrated that ultrathin films ∼100 nm thick fabricated using polymer 2 sustain the release of fluorescently labeled PAH for up to four days when incubated at pH 5.0. The synthetic approach used here is modular and tunable and can be used to introduce anionic 'charge-shifting' character to a broad range of other polyamines. With further development, this approach could expand significantly the range of different cationic agents (e.g., cationic proteins, peptides, polymers, nanoparticles, etc.) that can be released or delivered from surfaces using polyelectrolyte multilayers.
SPECT/CT hybrid imaging with 111In‐pentetreotide in assessment of neuroendocrine tumours (2003)

SPECT/CT affected the diagnostic interpretation of SRS in 32% of the patients and induced changes in management in 14% of the patients.
Insect immunity: molecular cloning, expression, and characterization of cDNAs and genomic DNA encoding three isoforms of insect defensin in Aedes aegypti (1999)

Aedes aegypti were immune activated by injection with bacteria, and the expression of insect defensins was measured over time. Northern analyses indicated that defensin transcriptional activity continued for at least 21 days after bacterial injection, and up to 10 days after saline inoculation. Mature defensin levels in the haemolymph reached approximately 45 microM at 24 h post inoculation. cDNAs encoding the preprodefensins of three previously described mature Ae. aegypti defensins were amplified by PCR, cloned and sequenced. Genomic clones were amplified using primers designed against the cDNA sequence. Sequence comparison indicates that there is significant inter- and intra-isoform variability in the signal peptide and prodefensin sequences of defensin genes. Preprodefensin sequences of isoforms A and B are very similar, consisting of a signal peptide region of twenty amino acids, a prodefensin region of thirty-eight amino acids and a forty amino acid mature peptide domain. The sequence encoding isoform C is significantly different, comprising a signal peptide region of twenty-three amino acids, a prodefensin region of thirty-six amino acids, and the mature protein domain of forty amino acids. Analysis of the genomic clones of each isoform revealed one intron spatially conserved in the prodefensin region of all sequences. The intron in isoforms A and B is 64 nt long, and except for a 4 nt substitution in one clone, these intron sequences are identical. The intron in isoform C is 76 nt long and does not share significant identity with the intron sequences of isoforms A or B. The defensin gene mapped to chromosome 3, between two known loci, blt and LF168.
Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription. (1991)

Leukocyte adherence to endothelium is in part mediated by the transient expression of endothelial-leukocyte adhesion molecule 1 (ELAM-1) on endothelial surfaces stimulated by tumor necrosis factor alpha (TNF), interleukin (IL) 1, or bacterial lipopolysaccharide (LPS). The intracellular factors controlling induction of ELAM-1 mRNA and protein are unknown. In nuclear runoff experiments with cultured human umbilical vein endothelial cells (HUVEC), we demonstrate that transcriptional activation of the ELAM-1 gene occurs following stimulation with TNF. Sequence analysis of the 5' flanking region of the ELAM-1 gene reveals consensus DNA-binding sequences for two known transcription factors, NF-kappa B and AP-1. Gel mobility shift assays demonstrate that TNF, IL-1, or LPS (but not IL-2, IL-4, IL-6, interferon gamma, histamine, or transforming growth factor beta) induces activation of NF-kappa B-like DNA binding activity in HUVEC. In contrast, neither TNF, IL-1, nor LPS activates proteins that bind to an AP-1 consensus sequence under these experimental conditions. Phorbol 12-myristate 13-acetate, a known activator of protein kinase C (PKC), weakly induces NF-kappa B-like activity, ELAM-1 mRNA, and ELAM-1 surface expression in HUVEC. However, TNF, IL-1, and LPS do not activate PKC in HUVEC at doses that strongly induce NF-kappa B-like protein activation and ELAM-1 gene expression. PKC blockade with H7 does not inhibit activation of these NF-kappa B-like proteins but does inhibit ELAM-1 gene transcription. We conclude that PKC-independent activation of NF-kappa B in HUVEC with TNF, IL-1, or LPS is associated with, but not sufficient for, activation of ELAM-1 gene transcription.
Humoral immune-response to naturally occurring STn in metastatic breast cancer patients (MBC pts) treated with STn-KLH vaccine (2004)

2547 Background: Theratope is an investigational therapeutic cancer vaccine consisting of a synthetic form of STn conjugated to KLH. Phase III study results showed a trend for increased survival in MBC pts concurrently treated with Theratope (T) and hormone therapy (HT) (38.2mo (T) vs. 30.7mo (control, C), Cox P= 0.07). Methods: MBC pts with no evidence of disease or non-progressive disease following any first-line chemotherapy were eligible for a randomized, controlled, double-blind, multicenter study. Study arms were adjuvant plus T or adjuvant plus KLH (C). All pts received a single IV dose of cyclophosphamide (300mg/m2) 72 hr before vaccine. Primary endpoints were overall survival (OS) and time to progression. Secondary endpoints were humoral (IgG) responses to the KLH (carrier), STn (synthetic monomeric form), and OSM (naturally occurring clustered STn) antigens in MBC pts +/- HT treated with T. IgG was measured using ELISA assays for STn, OSM, and KLH at week-12 of vaccine therapy. Median OS was prospectively assessed as a function of IgG titers. Results: Of a planned accrual of 950 pts, 1030 were enrolled and 1028 randomized to recive adjuvant + T(n=523) or C (n=505). As of September 2003, median duration of follow-up was 22.2 mo. Median titer of anti-OSM IgG was 320 in the T group and 0 in the C group. Median OS was significantly greater in T treated pts who received concurrent HT and who had IgG titers of anti-OSM equal to or higher than the median titer (41.1 vs. 25.4 mo, log-rank p=0.01) (see Table). OS was not influenced by anti-STn or anti-KLH titers, indicating that only titers of the naturally occurring clustered STn antigen are predictive of increased OS. Conclusions: Experimental vaccine trials suggest that the ability to mount an immune response is associated with favorable clinical outcomes. Our data from this large, prospective trial indicate that the magnitude of the immune response to the relevant and specific antigen is most predictive of a favorable clinical outcome. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biomira, Inc.; EMD Pharmaceuticals Biomira, Inc. Biomira, Inc.; EMD Pharmaceuticals Biomira, Inc.; Merck KGaA
Crystallization and Ionic Associations in Semicrystalline Ionomers (1998)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTCrystallization and Ionic Associations in Semicrystalline IonomersDaniel J. Quiram, Richard A. Register, and Anthony J. RyanView Author Information Department of Chemical Engineering, Princeton University, Princeton, New Jersey 08544-5263 Manchester Materials Science Centre, University of Manchester Institute of Science and Technology, Manchester M1 7HS, United Kingdom Cite this: Macromolecules 1998, 31, 4, 1432–1435Publication Date (Web):January 31, 1998Publication History Received15 July 1997Revised17 November 1997Published online31 January 1998Published inissue 1 February 1998https://pubs.acs.org/doi/10.1021/ma9710491https://doi.org/10.1021/ma9710491brief-reportACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views596Altmetric-Citations47LEARN 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 SUBJECTS:Crystallization,Crystals,Ionomers,Polymers,X-ray scattering Get e-Alerts
Exceedingly small iron oxide nanoparticles as positive MRI contrast agents (2017)

Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T<sub>1</sub> contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.
Highly Luminescent and Stable Hydroxypyridinonate Complexes: A Step Towards New Curium Decontamination Strategies (2014)

The photophysical properties, solution thermodynamics, and in vivo complex stabilities of Cm(III) complexes formed with multidentate hydroxypyridinonate ligands, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), are reported. Both chelators were investigated for their ability to act as antenna chromophores for Cm(III), leading to highly sensitized luminescence emission of the metal upon complexation, with long lifetimes (383 and 196 μs for 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), respectively) and remarkable quantum yields (45 % and 16 %, respectively) in aqueous solution. The bright emission peaks were used to probe the electronic structure of the 5f complexes and gain insight into ligand field effects; they were also exploited to determine the high (and proton-independent) stabilities of the corresponding Cm(III) complexes (log β110 = 21.8(4) for 3,4,3-LI(1,2-HOPO) and log β120 = 24.5(5) for 5-LIO(Me-3,2-HOPO)). The in vivo complex stability for both ligands was assessed by using (248) Cm as a tracer in a rodent model, which provided a direct comparison with the in vitro thermodynamic results and demonstrated the great potential of 3,4,3-LI(1,2-HOPO) as a therapeutic Cm(III) decontamination agent.
Effects of teleocidin and the phorbol ester tumor promoters on cell transformation, differentiation, and phospholipid metabolism. (1982)

The potent tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) and related diterpene phorbol esters have been shown to enhance viral transformation and anchorage-independent growth, inhibit differentiation, and stimulate phosphatidylcholine turnover in various cell culture systems. In the present study, we report that teleocidin, and indole alkaloid isolated from Streptomyces, induces several biological effects similar to those of TPA in cell culture. Both TPA and teleocidin enhanced transformation of a clone of Fischer rat embryo cells (CREF) by a temperature-sensitive mutant of adenovirus type 5 (H5ts125); enhanced the cloning efficiency in agar of E11 cells, a clone of H5ts125-transformed Sprague-Dawley rat embryo cells; inhibited melanogenesis in murine B-16 melanoma cells; inhibited myogenesis in myoblast cultures established from normal human skeletal muscle; and stimulated choline release from prelabeled phospholipids of C3H10T 1/2 mouse cells. In general, TPA and teleocidin were equipotent in inducing these biological effects and were most active in the 3- to 10-ng/ml range, i.e., approximately 10(-8) to 10(-9) M. These studies provide further evidence that teleocidin represents a new class of tumor-promoting agents with properties similar to, if not identical with, those of the phorbol ester tumor promoters. These findings also suggest that cell culture systems can be used to identify new types of tumor-promoting agents in addition to the diterpene phorbol esters.
Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptor-mediated transcription in vitro. (1992)

Metabolism of retinoic acid to a less active metabolite, 4-hydroxyretinoic acid, occurs via cytochrome P-450 isozyme(s). Effect of a pharmacological dose of retinoic acid on the level of retinoic acid in skin and on cytochrome P-450 activity was investigated. A cream containing 0.1% retinoic acid or cream alone was applied topically to adult human skin for four days under occlusion. Treated areas were removed by a keratome and a microsomal fraction was isolated from each biopsy. In vitro incubation of 3H-retinoic acid with microsomes from in vivo retinoic acid treated sites resulted in a 4.5-fold increase (P = 0.0001, n = 13) in its transformation to 4-hydroxyretinoic acid in comparison to in vitro incubations with microsomes from in vivo cream alone treated sites. This cytochrome P-450 mediated activity was oxygen- and NADPH-dependent and was inhibited 68% by 5 microM ketoconazole (P = 0.0035, n = 8) and 51% by carbon monoxide (P = 0.02, n = 6). Cotransfection of individual retinoic acid receptors (RARs) or retinoid X receptor-alpha (RXR-alpha) and a chloramphenicol acetyl transferase (CAT) reporter plasmid containing a retinoic acid responsive element into CV-1 cells was used to determine the ED50 values for stimulation of CAT activity by retinoic acid and its metabolites. Levels of all trans and 13-cis RA in RA-treated tissues were greater than the ED50 values determined for all three RARs with these compounds. Furthermore, the level of all trans RA was greater than the ED50 for RXR-alpha whereas the 4-OH RA level was greater than the ED50 for RAR-beta and RAR-gamma but less than for RAR-alpha and RXR-alpha. These data suggest that there are sufficient amounts of retinoic acid in treated skin to activate gene transcription over both RARs and RXR-alpha.
Evaluation of cancer therapy using diffusion magnetic resonance imaging. (2003)

Assessment of the effectiveness of cancer therapy traditionally relies on comparison of tumor images acquired before and after therapeutic intervention by inspection of gross anatomical images to evaluate changes in tumor size. The potential for imaging to provide additional insights related to the therapeutic impact would be enhanced if a specific parameter or combination of parameters could be identified that reflect tissue changes at the cellular or physiological level. This information could also provide a more sensitive and earlier indicator of treatment response in an individual animal or patient. Diffusion magnetic resonance imaging can detect relatively small changes in tissue structure at the cellular level and thus provides an opportunity to quantitatively and serially follow therapeutic-induced changes in solid tumors. This article provides an overview of the use of diffusion magnetic resonance imaging as a surrogate marker for quantitating treatment responsiveness in both preclinical and clinical studies.
Genetics of Rheumatoid Arthritis (1991)

Genetics of Rheumatoid Arthritis Get access J. S. S. LANCHBURY, J. S. S. LANCHBURY Rheumatology and Molecular Immunogenetics Units, Division of Medicine, UMDS, Guy's HospitalLondon SE1 9RT Search for other works by this author on: Oxford Academic PubMed Google Scholar L. I. SAKKAS, L. I. SAKKAS Rheumatology and Molecular Immunogenetics Units, Division of Medicine, UMDS, Guy's HospitalLondon SE1 9RT Search for other works by this author on: Oxford Academic PubMed Google Scholar K. I. WELSH, K. I. WELSH Rheumatology and Molecular Immunogenetics Units, Division of Medicine, UMDS, Guy's HospitalLondon SE1 9RT Search for other works by this author on: Oxford Academic PubMed Google Scholar G. S. PANAYI G. S. PANAYI Rheumatology and Molecular Immunogenetics Units, Division of Medicine, UMDS, Guy's HospitalLondon SE1 9RT Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 30, Issue 4, August 1991, Pages 319–320, https://doi.org/10.1093/rheumatology/30.4.319-a Published: 01 August 1991 Article history Accepted: 29 April 1991 Published: 01 August 1991
Potassium tert‐Butoxide‐Catalyzed Dehydrogenative SiO Coupling: Reactivity Pattern and Mechanism of an Underappreciated Alcohol Protection (2009)

A remarkable tert-butoxide-catalyzed coupling of alcohols and silanes is reported. Dihydrogen and not hydrochloric acid (generated in the prevalent, related coupling of alcohols and chlorosilanes) is formed as the sole by-product. A comprehensive survey of common silanes provides a reliable tool for the predictability of their reactivity under defined reaction conditions. The debated mechanism of this transformation is investigated monitoring the stereochemical course at the silicon atom by means of a silicon-stereogenic silane. On this basis, a transition state for the enantiospecific Si-O coupling step is suggested rationalizing the observed frontside attack and thus retention at the silicon atom.
Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v‐Ha‐ras oncogene (1993)

The regulatory elements of the human keratin K1 gene have been used to target expression of the v-Ha-ras oncogene exclusively in the epidermis of transgenic mice. We developed 12 transgenic mouse lines that express the HK1.ras transgene, producing epidermal hyperplasia in neonates and hyperkeratosis in juveniles. Eventually this skin phenotype diminished but with time adult animals developed papillomas that could persist or regress. The rate and frequency of tumorigenesis appeared to be limited, which suggests that v-Ha-ras requires a second or even third event to elicit and maintain a benign phenotype in transgenic mice. Since in certain transgenic lines papillomas appeared at wound sites, it appears that the promotion stimulus from wounding may be a second event. We envision that such transgenic mice that express v-Ha-ras in the epidermis will become a powerful model for assessing how environmental and molecular factors affect the process of multistage skin carcinogenesis in vivo, as well as a model for evaluating novel therapeutic protocols.
VariantASGR1Associated with a Reduced Risk of Coronary Artery Disease (2016)

ASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health and others.).
A New Medicago truncatula Line with Superior in Vitro Regeneration, Transformation, and Symbiotic Properties Isolated Through Cell Culture Selection (1997)

The understanding of how leguminous plants establish symbiosis with rhizobia is limited by the lack of genetic system in most legume plants. Here we propose a Medicago truncatula line suitable for genetic analysis of Medicago-Rhizobium meliloti symbiosis because of its high regeneration capacity and broad R. meliloti strain specificity. This line has been isolated by extensive in vitro screening of explants from several ecotypes of M. truncatula that are known to be autogamous and have small diploid genomes. One such derivative identified from ecotype 108-1 has gained the capacity to be readily regenerated in vitro. The derivative, called R108-1, like its parent, can establish effective symbiosis with several widely studied R. meliloti strains (Rm41, Rm2011, Rm1021, F51, and GR4). Importantly, the nodulation characteristics of the R108-1 line were not compromised by the in vitro selection procedure. We have further established the conditions for efficient transformation of R108-1 by co-cultivation with Agrobacterium tumefaciens. Thus, this in vitro-derived plant line has most of the favorable attributes, otherwise rare among legumes, of a complementary model plant system for investigating symbiosis at the genetic and the molecular levels.