gebhart/patrepeval huggingface dataset:
Helplessness as a strategy for avoiding antiglobulin responses to therapeutic monoclonal antibodies. (1994)

The antiglobulin (anti-Ig) response to therapeutic monoclonal antibodies (mAbs) poses a significant obstacle to their routine application in man. Whilst humanization has lessened the problem, repeated courses of humanized mAbs still sensitise some patients. Previous work suggested that unresponsiveness to cell-binding (therapeutic) mAbs could not be achieved due to an unexpected immunogenicity of their idiotypes (ids). The current work examines this phenomenon in more detail using CBA/Ca mice receiving rat antimouse CD8 mAbs as a model system. It is shown that the anti-Ig response is dependent on CD4+ T-cells. Furthermore, for at least some mAbs, most helper epitopes appear to reside within the mAb c-region. Consequently, when tolerance is induced to c-region (isotype), the anti-id response is extremely weak (induced helplessness). For one (weakly immunogenic) CD8 mAb concomitant administration of a CD4 mAb was sufficient to induce tolerance, whereas for another (more immunogenic) CD8 mAb, tolerance could only be achieved by prior concomitant exposure to both a CD4 mAb and an isotype-matched non-cell-binding mAb. The general applicability of these results is discussed and extrapolated to the clinical situation. Non-cell-binding variants of therapeutic mAbs could be usefully exploited to generate therapeutic unresponsiveness to any clinically useful mAb.
The mentor’s tale: a reflexive account of semi-structured interviews (2003)

In this article, Helen Hand provides an account of personal experience as a novice researcher collecting data using semi-structured interviews. The data were collected as part of a study involving nurse mentors who had had the experience of mentoring and subsequently failing a student nurse. The paper emphasises the importance of reflexivity as a method of signposting to the reader 'what is going on' in the research process. In conclusion, it is suggested that creating the 'joint account' is a complex but worthwhile task, but that great skill is required by the researcher in order to participate in the construction of reality.
FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction (2006)

Mammalian cardiomyocytes have limited proliferation potential, and acutely injured mammalian hearts do not regenerate adequately. Instead, injured myocardium develops fibrosis and scarring. Here we show that FGF1/p38 MAP kinase inhibitor treatment after acute myocardial injury in 8- to 10-week-old rats increases cardiomyocyte mitosis. At 3 months after injury, 4 weeks of FGF1/p38 MAP kinase inhibitor therapy results in reduced scarring and wall thinning, with markedly improved cardiac function. In contrast, p38 MAP kinase inhibition alone fails to rescue heart function despite increased cardiomyocyte mitosis. FGF1 improves angiogenesis, possibly contributing to the survival of newly generated cardiomyocytes. Our data indicate that FGF1 and p38 MAP kinase, proteins involved in cardiomyocyte proliferation and angiogenesis during development, may be delivered therapeutically to enhance cardiac regeneration.
Mixture-Based Heterocyclic Combinatorial Positional Scanning Libraries: Discovery of Bicyclic Guanidines Having Potent Antifungal Activities against Candida albicans and Cryptococcus neoformans (1999)

A mixture-based synthetic combinatorial library of more than 100,000 bicyclic guanidines was generated in a positional scanning format and assayed for activity against Candida albicans. Potent individual bicyclic guanidines were directly identified following the screening of the library. Time-kill curve studies indicated bactericidal activities for the individual bicyclic guanidines. These compounds also showed potent activity against Cryptococcus neoformans. These studies demonstrate the value of using mixture-based combinatorial positional scanning libraries made up of heterocyclic compounds for the rapid identification of novel classes of antifungal compounds.
Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes. (2000)

Neutrophils from diabetic animals exhibit higher levels of surface integrin expression and integrin-mediated adhesion. In vivo, CD18 blockade significantly decreases leukostasis in the diabetic retinal microvasculature. Integrin adhesion molecules may serve as therapeutic targets for the treatment and/or prevention of early diabetic retinopathy.
Modified BINOL Ligands in Asymmetric Catalysis (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTModified BINOL Ligands in Asymmetric Catalysis†Yu Chen, Shahla Yekta, and Andrei K. YudinView Author Information Davenport Building, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada Cite this: Chem. Rev. 2003, 103, 8, 3155–3212Publication Date (Web):August 13, 2003Publication History Received20 February 2003Published online13 August 2003Published inissue 1 August 2003https://pubs.acs.org/doi/10.1021/cr020025bhttps://doi.org/10.1021/cr020025bresearch-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views14823Altmetric-Citations868LEARN 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:Aldehydes,Catalysts,Ligands,Reaction products,Stereoselectivity Get e-Alerts
NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma (2007)

The oncogenic fusion tyrosine kinase nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) induces cellular transformation in anaplastic large-cell lymphomas (ALCLs) carrying the t(2;5) chromosomal translocation. Protein-protein interactions involving NPM/ALK are important for the activation of downstream signaling pathways. This study was aimed at identifying novel NPM/ALK-binding proteins that might contribute to its oncogenic transformation. Using a proteomic approach, several RNA/DNA-binding proteins were found to coimmunoprecipitate with NPM/ALK, including the multifunctional polypyrimidine tract binding proteinassociated splicing factor (PSF). The interaction between NPM/ALK and PSF was dependent on an active ALK kinase domain and PSF was found to be tyrosine-phosphorylated in NPM/ALK-expressing cell lines and in primary ALK(+) ALCL samples. Furthermore, PSF was shown to be a direct substrate of purified ALK kinase domain in vitro, and PSF Tyr293 was identified as the site of phosphorylation. Y293F PSF was not phosphorylated by NPM/ALK and was not delocalized in NPM/ALK(+) cells. The expression of ALK fusion proteins induced delocalization of PSF from the nucleus to the cytoplasm and forced overexpression of PSF-inhibited proliferation and induced apoptosis in cells expressing NPM/ALK. PSF phosphorylation also increased its binding to RNA and decreased the PSF-mediated suppression of GAGE6 expression. These results identify PSF as a novel NPM/ALK-binding protein and substrate, and suggest that PSF function may be perturbed in NPM/ALK-transformed cells.
Rhodium(III)-Catalyzed Direct Selective C(5)–H Oxidative Annulations of 2-Substituted Imidazoles and Alkynes by Double C–H Activation (2013)

Double C-H activations of C(5)-H and Csp(2)-H of 2-substituted N-vinyl- or arylimidazoles were realized without heteroatom-directing assistance by rhodium(III) catalyst. A subsequent oxidative annulation reaction with alkynes efficiently produced aza-fused heterocycles with high molecular complexity in low to excellent yields.
Neuroinflammation drives anxiety and depression in relapsing-remitting multiple sclerosis (2017)

Mood alterations are induced by intrathecal inflammation, even though not clinically apparent, and are able to predict inflammatory reactivations in RRMS. Inflammation is therefore a biological event, not less important than the traditional psychosocial factors, involved in mood disorders.
3,5′-Anhydrosynadenol, ein polycyclisches Anhydronucleosid-Analogon (1998)

Cyclisierung statt O-Phosphorylierung ist das Ergebnis der Umsetzung des stark virostatischen Nucleosid-Analogons 1 mit reaktiven Phosphorylierungsreagentien. Die Bildung des neuartigen Polycyclus 2 beweist, daß 1 (Z)-konfiguriert ist, und diese Konfiguration ist wichtig für die antivirale Aktivität von 1 und verwandten Verbindungen.
Mass cytometry deep phenotyping of human mononuclear phagocytes and myeloid-derived suppressor cells from human blood and bone marrow (2017)

The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274. MPS diversity was characterized for 1) circulating monocytes from healthy donors, 2) monocyte-derived macrophages further polarized in vitro (i.e., M-CSF, GM-CSF, IL-4, IL-10, IFN-γ, or LPS long-term stimulations), 3) monocyte-derived DCs, and 4) myeloid-derived suppressor cells (MDSCs), generated in vitro from bone marrow and/or peripheral blood. Known monocyte subsets were detected in peripheral blood to validate the panel and analysis pipeline. Then, using various culture conditions and stimuli before CyTOF analysis, we constructed a multidimensional framework for the MPS compartment, which was registered against historical M1 or M2 macrophages, monocyte subsets, and DCs. Notably, MDSCs generated in vitro from bone marrow expressed more S100A9 than when generated from peripheral blood. Finally, to test the approach in vivo, peripheral blood from patients with melanoma (<i>n</i> = 5) was characterized and observed to be enriched for MDSCs with a phenotype of CD14<sup>+</sup>HLA-DR<sup>low</sup>S100A9<sup>high</sup> (3% of PBMCs in healthy donors, 15.5% in patients with melanoma, <i>P</i> < 0.02). In summary, mass cytometry comprehensively characterized phenotypes of human monocyte, MDSC, macrophage, and DC subpopulations in both in vitro models and patients.
Genetic analysis of factors for resistance to downy mildew ( Bremia lactucae ) in species of lettuce ( Lactuca sativa and L. serriola ) (1987)

Simultaneous genetic analysis of resistance in species of lettuce (Lactuca sativa and L. serriola) and a virulence in Bremia lactucae were made to characterize the genetic basis of resistance to downy mildew in 11 host cultivars and accessions. Four new downy mildew resistance genes (Dm13, Dm14, Dm15 and Dm16) were characterized. Other resistance phenotypes were conditioned by combinations of these or previously described Dm genes. New resistance genes, Dm 16 (from LSE/18), Dm14 (from Gelber Winterkonig) and Dm15 (from PIVT 1309), mapped to Dm linkage group I (Dm1, Dm2, Dm3 and Dm6) while Dm13 from Pennlake segregated independently of the three previously characterized linkage groups and therefore belongs to a fourth linkage group. Characterization of new resistance genes requires simultaneous consideration of host and pathogen genetics.
Spinal nerve ligation: what to blame for the pain and why (2000)

University of Maryland, Baltimore Dental School, Department of Oral and Craniofacial Biological Sciences, 666 West Baltimore Street, Baltimore, MD 21201, USA * Tel.: +1-410-706-5117; fax: +1-410-706-0865 E-mail address:[email protected] Received November 29, 1999; accepted December 2, 1999
Effect of plasma and thermal annealing on chemical vapor deposition dielectrics grown using SIH4–H2O2 gas mixtures (1997)

Silicon dioxide has been deposited at low pressure (1 Torr) and low substrate temperature (0 °C) by chemical vapor deposition (CVD) using SiH4 and hydrogen peroxide (H2O2) concentrated at 30% or 60%. The effect of solution concentration on film properties has been investigated: characterization of the deposited films has been carried out by ex situ Fourier transform infrared spectroscopy, ellipsometry, and mechanical stress measurements. For shallow trench isolation applications, the physical and electrical properties of the CVD oxide must be close to those of a thermal oxide. Such properties can be obtained by in situ annealing.
Comparative production and rapid purification of Candida acid proteinase from protein-supplemented cultures (1990)

Six Candida spp. that were previously characterized for cutaneous pathogenicity were assessed for Candida acid proteinase (CAP) production in albumin-supplemented, nitrogen-restricted media. C. albicans CAP production was compared in media supplemented with albumin, casein, collagen, hemoglobin, or keratin and in TC medium 199. C. albicans, C. stellatoidea, and C. tropicalis, which are cutaneous pathogens in murine infections, produced 3.3 to 4.7 times more CAP than did the nonpathogens C. parapsilosis and C. guilliermondii. C. krusei, a nonpathogen, produced negligible amounts of enzyme. C. albicans CAP production was similar in each protein-supplemented medium, and only a single acid proteinase was recovered from each one. Rapid CAP purification from culture supernatants was achieved by hollow fiber and stirred cell ultrafiltration followed by Affi-Gel blue and Sephacryl column chromatographies. The highest yield, purity, and specific activity of CAP were obtained from keratin-supplemented medium supernatants, producing 2.86 mg of purified CAP from a 7-liter culture. CAP was characterized as a 41,500-dalton glycoprotein, with a pI of 4.5; a pH range of 2.5 to 5.5; and broad substrate specificity, including that for keratin, denatured collagen, hemoglobin, casein, and albumin. Isolation of CAP also isolated the keratinolytic proteinase of Candida spp. CAP was inhibited by pepstatin A, but not by EDTA or phenylmethylsulfonyl fluoride. Monospecific antibody to CAP was produced in mice and reacted only to the 41,500-dalton protein, as determined by immunoblot analysis. High CAP production by cutaneous pathogenic Candida spp. supports the fact that CAP is a potential virulence factor that may facilitate Candida colonization and invasion of skin. CAP production from keratin-supplemented medium was superior to that from the other media that were tested and yielded sufficient and suitable enzyme for use in immunoassays of CAP antigen and antibody.
The exogenous form of Jaagsiekte retrovirus is specifically associated with a contagious lung cancer of sheep (1996)

Sheep pulmonary adenomatosis ([SPA] ovine pulmonary carcinoma) is a transmissible lung cancer of sheep that has been associated etiologically with a type D- and B-related retrovirus (jaagsiekte retrovirus (JSRV]). To date it has been impossible to cultivate JSRV in vitro and therefore to demonstrate the etiology of SPA by a classical approach. In addition, the presence of 15 to 20 copies of endogenous JSRV-related sequences (enJSRV) has hampered studies at the molecular level. The aim of this study was to investigate whether the expression of exogenous JSRV was specifically associated with neoplasia in SPA-affected animals. Initially, we found that enJSRVs were transcribed in a wide variety of normal sheep tissues. Then, by sequencing part of the gag gene of enJSRV we established a ScaI restriction site in gag as a molecular marker for the exogenous form of JSRV. Restriction enzyme digestion of PCR products obtained from the amplification of cDNA from a total of 65 tissues collected from SPA-affected and unaffected control sheep revealed that the exogenous form of JSRV was exclusively and consistently present in tumor tissues and lung secretions of the affected animals. In addition, exogenous JSRV provirus was detected only in DNA from SPA tumors and not from nontumor tissues of the same animals. This study has demonstrated clearly that the exogenous form of JSRV is specifically associated with SPA tumors.
Molding of Hydrogel Microstructures to Create Multiphenotype Cell Microarrays (2003)

The fabrication of mammalian cell-containing poly(ethylene glycol) (PEG) hydrogel microstructures on glass and silicon substrates is described. Using photoreaction injection molding in poly(dimethylsiloxane) microfluidic channels, three-dimensional hydrogel microstructures encapsulating cells (fibroblasts, hepatocytes, macrophage) were fabricated with cells uniformly distributed to each hydrogel microstructure, and the number of cells in each hydrogel microstructure was controlled by changing the cell density of the precursor solution. PEG hydrogels were modified using an Arg-Gly-Asp (RGD) peptide sequence, with the incorporation of RGD into the hydrogel matrix promoting the spreading of encapsulated fibroblasts over a 24-h period in culture. Cells remained viable encapsulated in these hydrogel microstructures for a period in excess of 1 week in culture. Arrays of hydrogel microstructures encapsulating two or more phenotypes on a single substrate were successfully fabricated using multimicrofluidic channels, creating the potential for multiphenotype cell-based biosensors.
Development of an advanced polysome display system dependant on a specific protein-RNA motif interaction (2001)

The ribosome display system is a very powerful too for in vitro screening of mRNAs that encode proteins (or peptides) with specific (known and unknown) functions. The ribosome display system depends on the stability of ribosome-mRNA complexes that have been achieved by the removal of a stop codon. An additional interaction we employed was between tandem fused MS2 coat protein (MSp) dimer and the RNA of its specific motif called a "C-variant" (or "Cv"). The MSp dimer and the Cv were placed at the N-terminal end of a nascent protein translated in vitro and the 5'-end of its mRNA, that might circularize the polysome complex and, as a result, further stabilize the ribosome-mRNA complex. The selectivity of mRNAs after selection was increased 2-fold by the introduction of the interaction between the MSp dimer and Cv.
1fnoise and other slow, nonexponential kinetics in condensed matter (1988)

Fluctuations in resistivity with an approximately $\frac{1}{f}$ spectrum are found in most conducting materials. Some of the detailed mechanisms, which turn out to be quite diverse, are explored in this review. Several new techniques are explained. Various theories are critically examined. Some connections with other widespread phenomena, such as highly nonexponential dielectric relaxations, are briefly investigated.
Gut Microbiota: A Perspective for Psychiatrists (2019)

There is mounting evidence that the trillions of microbes that inhabit our gut are a substantial contributing factor to mental health and, equally, to the progression of neuropsychiatric disorders. The extraordinary complexity of the gut ecosystem, and how it interacts with the intestinal epithelium to manifest physiological changes in the brain to influence mood and behaviour, has been the subject of intense scientific scrutiny over the last 2 decades. To further complicate matters, we each harbour a unique microbiota community that is subject to change by a number of factors including diet, exercise, stress, health status, genetics, medication, and age, amongst others. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the gastrointestinal (GI) microbiota, immune cells, gut tissue, glands, the autonomic nervous system (ANS), and the brain that communicate in a complex multidirectional manner through a number of anatomically and physiologically distinct systems. Long-term perturbations to this homeostatic environment may contribute to the progression of a number of disorders by altering physiological processes including hypothalamic-pituitary-adrenal axis activation, neurotransmitter systems, immune function, and the inflammatory response. While an appropriate, co-ordinated physiological response, such as an immune or stress response, is necessary for survival, a dysfunctional response can be detrimental to the host, contributing to the development of a number of central nervous system disorders.
Murine mucopolysaccharidosis type VII: The impact of therapies on the clinical course and pathology in a murine model of lysosomal storage disease (1998)

Murine mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a recessively inherited deficiency of the lysosomal enzyme beta-glucuronidase. Affected mice have clinical, biochemical and pathological findings similar to those seen in humans with MPS VII (Sly syndrome), including growth retardation, facial dysmorphism, deafness, behavioural deficits and widespread glycosaminoglycan storage in lysosomes in the viscera, skeleton and brain. This mouse model is a useful tool for the evaluation of the effectiveness and experimental therapies for the MPS disorders. Syngeneic bone marrow transplantation performed in newborn MPS VII animals--before clinical evidence of disease is pronounced--prolongs life, improves hearing and bone growth, and prevents lysosomal storage in many sites, but does not correct the central nervous system disease. Enzyme therapy with beta-glucuronidase from the first days of life does reduce lysosomal storage in the brain in murine MPS VII. The enzyme-replaced mice also have reduced visceral lysosomal storage, impressive normalization of their phenotype and an improved life span. The effectiveness of gene therapy for the treatment of lysosomal storage disease has also been tested using the MPS VII model. When transplanted into MPS VII mice, syngeneic haematopoietic stem cells or mouse skin fibroblasts infected with retrovirus expressing beta-glucuronidase decreased storage, but only in the liver and spleen. Injection of an adenovirus vector expressing beta-glucuronidase into the vitreous of the MPS VII mice reduced storage in the retinal pigment epithelium and corneal endothelium. Intravenous administration of the adenovirus vector transduced with the beta-glucuronidase gene reduced liver and spleen storage and, when instilled into the cerebral ventricles, this viral vector caused beta-glucuronidase production in epithelial cells lining the ventricles. Recently, retroviral vector-corrected MPS VII fibroblasts secreting high levels of beta-glucuronidase were engrafted directly into the brains of adult MPS VII mice with resultant reduction in storage in neurons and glia adjacent to the grafts. Future efforts aimed at prolonging expression of the beta-glucuronidase gene by viral vectors and more precisely directing the therapeutic effect to the skeleton and brain will be important in optimizing treatments for murine MPS VII and extending the results of such therapies to humans with MPS.