gebhart/patrepeval huggingface dataset:
Electron microscopic studies of sequence‐specific recognition of duplex DNA by different ligands (1994)

The following ligands were used to study sequence specific recognition of duplex DNA by electron microscopic techniques: methyltransferases BspR1 and EcoR124 (recognition sequences GGCC and GAAN7RTCG, respectively), a biotinylated deoxyoligonucleotide 5'-CTCTCTCTCTCTCT-3' capable of forming triplex DNA, and PNA oligomer H-T10-LysNH2. For each ligand the best conditions for electron microscopic (EM) detection of stable specific complex formation were determined. It was demonstrated that EM allowed us to determine the position of the individual target site with an error of 15-20 bp, the relative affinities for individual target sites and kinetic parameters of the binding. These results open new possibilities for EM investigations of sequence-specific interactions with a wide range of other ligands of a similar nature. They also imply that a wide range of different sequences can be unambiguously and precisely mapped by EM and greatly extend the scope of EM applications for physical mapping of genomic DNA.
Catalysis in inverted supercritical CO2/aqueous biphasic media (2002)

A new inverted biphasic catalysis system using supercritical CO2 as the stationary catalyst phase and water as the continuous phase is described for Rh-catalysed hydroformylation of polar substrates. Product separation and catalyst recycling is possible without depressurising the autoclave. Turnover numbers of up to 3560 were obtained in three consecutive runs and Rh leaching into the aqueous phase was below 0.3 ppm. The absence of organic solvents allows convenient product isolation from the aqueous layer without the need for waste water treatment.
Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs (2005)

Hepcidin is the principal iron regulatory hormone and its overproduction contributes to anemia of inflammation (AI). In vitro, hepcidin binds to and induces the degradation of the exclusive iron exporter ferroportin. We explored the effects and distribution of synthetic hepcidin in the mouse. A single intraperitoneal injection of hepcidin caused a rapid fall of serum iron in a dose-dependent manner, with a 50-microg dose resulting in iron levels 80% lower than in control mice. The full effect was seen within only 1 hour, consistent with a blockade of iron export from tissue stores and from macrophages involved in iron recycling. Serum iron remained suppressed for more than 48 hours after injection. Using radiolabeled hepcidin, we demonstrated that the serum concentration of hepcidin at the 50-microg dose was 1.4 microM, consistent with the inhibitory concentration of 50% (IC50) of hepcidin measured in vitro. Radiolabeled hepcidin accumulated in the ferroportin-rich organs, liver, spleen, and proximal duodenum. Our study highlights the central role of the hepcidin-ferroportin interaction in iron homeostasis. The rapid and sustained action of a single dose of hepcidin makes it an appealing agent for the prevention of iron accumulation in hereditary hemochromatosis.
The Tumor Suppressors p53, p63, and p73 Are Regulators of MicroRNA Processing Complex (2010)

The tumor suppressors p53, p73, and p63 are known to function as transcription factors. They promote either growth arrest or apoptosis, depending upon the DNA damage. A number of microRNAs (miRNAs) have been shown to function as transcriptional targets of p53 and they appear to aid p53 in promoting growth arrest and apoptosis. However, the question of p53/p63/p73 regulating the miRNA processing complex has not been addressed in depth so far. Comparative/computational genomic analysis was performed using Target scan, Mami, and Diana software to identify miRNAs that regulate the miRNA processing complex. Here, I present evidence for the first time that the tumor suppressors p53, p63, and p73 function as both positive and negative regulators of the miRNA processing components. Curated p53-dependent miRNA expression data was used to identify p53-miRs that target the components of the miRNA-processing complex. This analysis suggests that most of the components (mRNAs' 3'UTR) of the miRNA processing complex are targeted by p53-miRs. Remarkably, this data revealed the conserved nature of p53-miRs in targeting a number of components of the miRNA processing complex. p53/p73/p63 appears to regulate the major components of the miRNA processing, such as Drosha-DGCR8, Dicer-TRBP2, and Argonaute proteins. In particular, p53/p73/p63 appears to regulate the processing of miRNAs, such as let-7, miR-200c, miR-143, miR-107, miR-16, miR-145, miR-134, miR-449a, miR-503, and miR-21. Interestingly, there seems to be a phenotypic similarity between p63(-/-) and dicer(-/-) mice, suggesting that p63 and dicer could regulate each other. In addition, p63, p73, and the DGCR8 proteins contain a conserved interaction domain. Further, promoters of a number of components of the miRNA processing machinery, including dicer and P2P-R, contain p53-REs, suggesting that they could be direct transcriptional targets of p63/p73/p53. Together, this study provides mechanistic insights into how p53, p63, and p73 regulate the components of the miRNA processing; and how p53, TA-p63, and TA-p73 regulated miRNAs inhibit tumorigenesis, EMT, metastasis, and cancer stem cell proliferation.
The IgM CH2 domain as covalently linked homodimerization module for the generation of fusion proteins with dual specificity (2012)

Dimeric assembly of antibody fragments and other therapeutic molecules can result in increased binding and improved bioactivity. Here, we investigated the use of the IgM heavy chain domain 2 (MHD2) as covalently linked homodimerization module. Fusion of single-chain fragment variable (scFv) molecules directed against epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 to the N- and/or C-terminus of the MHD2, respectively, resulted in molecules with single or dual specificity for tumor cells. Bispecific tetravalent molecules were further generated by fusing a bispecific single-chain diabody directed against EGFR and epithelial cell adhesion molecule to the N-terminus of the MHD2. By combining an anti-EGFR scFv with a single-chain derivative of tumor necrosis factor, a tetravalent bifunctional fusion protein was produced. This fusion protein exhibited improved TNF activity, also mimicking the membrane-bound form of TNF, as shown by the activation of TNFR2-mediated cell killing. Furthermore, the scFv moiety allowed for an antigen-dependent delivery of TNF to EGFR-positive cells and an improved stimulatory TNF action on these cells. Thus, we established the MHD2 as a versatile module for the generation of bispecific and bifunctional fusion proteins.
Requirement of Metabotropic Glutamate Receptors for the Generation of Inflammation‐evoked Hyperexcitability in Rat Spinal Cord Neurons (1994)

In the central nervous system the transmitter L-glutamate activates both ionotropic receptors coupled to cation channels and metabotropic receptors coupled to G-proteins. The role of metabotropic receptors in the processing of mechanosensory and nociceptive information was studied in a subset of spinal cord neurons with afferent input from the knee joint in anaesthetized rats using electrophysiological methods. The ionophoretic administration of L-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist at the metabotropic receptor, had no effect on the responses to innocuous and noxious pressure applied to the normal knee joint, although the antagonist prevented the potentiation of these responses evoked by the ionophoretic administration of a specific agonist at the metabotropic receptor, trans-(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid (t-ACPD). By contrast, in neurons that were rendered hyperexcitable by acute inflammation in the knee joint L-AP3 reduced the responses to pressure applied to the knee. When L-Ap3 was applied during induction of inflammation and throughout the subsequent 1.5 h the spinal neurons did not develop hyperexcitability over this time period. L-AP3 did not impair the activation of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA receptors by the specific agonists. We conclude that spinal metabotropic glutamate receptors are not involved in the mediation of responses to innocuous and noxious mechanical stimuli applied under normal conditions. They are required, however, for the generation of inflammation-evoked hyperexcitability of spinal cord neurons, a form of functional plasticity underlying the painfulness in pathophysiological conditions such as inflammation.
Thermal conductance of epitaxial interfaces (2003)

The thermal conductance of interfaces between epitaxial TiN and single crystal oxides is measured at temperatures between 79.4 and 294 K using time-domain thermoreflectance. The analysis method relies on the ratio of the in-phase and out-of-phase signals of the lock-in amplifier for more accurate data analysis. The validity of this approach is tested by measurements on 6.5, 11.8, and 25 nm thick thermally oxidized ${\mathrm{SiO}}_{2}$ on Si. The thermal conductances G of TiN/MgO(001), TiN/MgO(111), and ${\mathrm{T}\mathrm{i}\mathrm{N}/\mathrm{A}\mathrm{l}}_{2}{\mathrm{O}}_{3}(0001)$ interfaces are essentially identical and in good agreement with the predictions of lattice dynamics models and the diffuse mismatch model with a four-atom fcc unit cell. Near room temperature, $G\ensuremath{\approx}700{\phantom{\rule{0ex}{0ex}}\mathrm{M}\mathrm{W}\mathrm{m}}^{\ensuremath{-}2}\phantom{\rule{0ex}{0ex}}{\mathrm{K}}^{\ensuremath{-}1},$ $\ensuremath{\approx}5$ times larger than the highest values reported previously for any individual interface.
Direct Contact between T Lymphocytes and Human Dermal Fibroblasts or Synoviocytes Down-regulates Types I and III Collagen Production via Cell-associated Cytokines (1998)

In many inflammatory diseases where tissue remodeling occurs, T cells are in close contact with mesenchymal cells. We investigated the effect of direct cell-cell contact between peripheral blood T lymphocytes or HUT-78 lymphoma cells and dermal fibroblasts or synoviocytes on the deposition of the major extracellular matrix components: types I and III collagen. Incubation of dermal fibroblasts and synoviocytes with plasma membrane preparations from resting T cells slightly increased the production of collagen I but did not significantly affect that of collagen III. Conversely, direct contact with either plasma membranes or fixed phytohemagglutinin/phorbol myristate acetate-activated T cells markedly inhibited the synthesis of types I and III collagen by 60-70% in untreated dermal fibroblasts and synoviocytes and by 85% in transforming growth factor beta-stimulated fibroblasts. This decrease of collagen synthesis was abrogated when fixed T cells were separated physically from fibroblasts, demonstrating that direct contact between the two cell types was necessary. This inhibition was associated with a marked decrease in steady-state levels of pro-alpha1(I) and pro-alpha1(III) collagen mRNAs. T cell contact decreased the transcription rate but did not significantly alter the stability of the alpha1(I) and alpha1(III) transcripts. Finally, using neutralizing antibodies or cytokine inhibitors we provide evidence that this inhibition of extracellular matrix production mediated by T cell contact was partially due to additive effects of T cell membrane-associated interferon gamma, tumor necrosis factor alpha, and interleukin-1alpha.
Met expression and sarcoma tumorigenicity. (1993)

The met protooncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signaling system in which cells of mesenchymal origin produce the ligand, which binds to the receptor that is predominantly expressed in cells of epithelial origin. However, mouse NIH/3T3 fibroblasts overexpressing Met induce tumor formation in nude mice via an autocrine mechanism (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that human cell lines established from various sarcomas express high levels of activated Met receptor. HGF/SF is also detected in the human sarcoma cell lines but at a reduced level when compared to primary fibroblasts. These properties, high Met expression and reduced ligand levels, are indistinguishable from the properties of NIH/3T3 tumor explant cells overexpressing Met (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992; S. Rong et al., Cell Growth & Differ., 4: 563-569, 1993). Moreover, paraffin-embedded sections of primary tumors from human osteosarcomas, chondrosarcomas, and leiomyosarcoma stain intensely for Met and/or HGF/SF and display extensive tumor cell heterogeneity with regard to both paracrine and autocrine stimulation. On the basis of these findings, we propose that Met-HGF/SF autocrine signaling may contribute to the tumorigenic process in human sarcomas.
Rate of change of angular momentum and balance maintenance of biped robots (2004)

In order to engage in useful activities, upright legged creatures must be able to maintain balance. Despite recent advances, the understanding, prediction and control of biped balance in realistic dynamical situations remain an unsolved problem and the subject of much research in robotics and biomechanics. Here we study the fundamental mechanics of the rotational stability of multi-body systems with the goal of identifying a general stability criterion. Our research focuses on H/sub G/, the rate of change of centroidal angular momentum of a robot, as the physical quantity containing its stability information. We propose three control strategies using H/sub G/ that can be used for stability recapture of biped robots. For free walk on horizontal ground, a derived criterion refers to a point on the foot/ground surface of a robot where the total ground reaction force would have to act such that H/sub G/=0. This new criterion generalizes earlier concepts such as GCoM, CoP, ZMP, and FRI point, and extends their applicability.
Finding idle machines in a workstation-based distributed system (2003)

The design and performance of scheduling facilities for finding idle hosts in a workstation-based distributed system are described. The focus is on the tradeoffs between centralized and decentralized architectures with respect to scalability, fault tolerance, and simplicity of design, as well as several implementation issues of interest when using multicast communication. It is concluded that the principal tradeoff between the two approaches is that a centralized architecture can be scaled to a significantly greater degree and can more easily monitor global system statistics, while a decentralized architecture is simpler to implement.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Genomic changes in endometrial polyps associated with tamoxifen show no evidence for its action as an external carcinogen. (1998)

Eighty-eight endometrial specimens from 36 postmenopausal breast cancer patients treated with tamoxifen were investigated cytogenetically and molecularly using fluorescence in situ hybridization with appropriate probes for the HMGIC and HMGIY genes. Twenty control specimens, 10 endometrial polyps, and 10 endometrial biopsy specimens were investigated in the same way. Of the 88 specimens, 44 were from endometrial polyps; 3 were from endocervical polyps; 7 were from cystic endometrium; 30 were from normal or atrophic endometrium, normal endocervix, or myometrium; and 4 were from endometrial carcinomas. Chromosome investigation of the endometrial polyps showed the nature of the chromosome changes in tamoxifen-induced polyps to be the same as that in the controls and in sporadic endometrial polyps described in the literature. HMGIC and HMGIY gene rearrangements in both groups were identical as shown by fluorescence in situ hybridization, which also allowed for the detection of seven hidden paracentric inversions involving 12q15, one of which occurred in a cystic endometrium. The carcinomas did not exhibit any of these changes. Because abnormal expression of HMGIC or HMGIY as a consequence of structural chromosome changes in 12q15 or 6p21, respectively, is invariably associated with benign neoplasia, tamoxifen-associated endometrial polyps are unlikely to undergo further malignant transformation, and a mode of action of tamoxifen as an external carcinogen is unlikely.
Identification of the Translation Products of Human Fibroblast Interferon mRNA in Reticulocyte Lysates (1979)

Messenger RNA was purified from human foreskin fibroblasts FS11, a high interferon-producer line, after induction with synthetic double-stranded RNA. The mRNA was translated in a cell-free protein-synthesis system from rabbit reticulocytes. The translation products, containing biologically active human interferon, were immunoprecipitated by a serum from rabbits immunized against partially purified interferon. Analysis of the immunoprecipitate by polyacrylamide gel electrophoresis in dodecylsulfate shows that the product of human fibroblast interferon mRNA is a 23000-Mr polypeptide. Methods are described for the synthesis and rapid identification of this polypeptide, which should be useful for structural analysis of interferon and isolation of its mRNA.
Benzo[a]pyrene-nucleic acid derivative found in vivo: structure of a benzo[a]pyrenetetrahydrodiol epoxide-guanosine adduct (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBenzo[a]pyrene-nucleic acid derivative found in vivo: structure of a benzo[a]pyrenetetrahydrodiol epoxide-guanosine adductA. M. Jeffrey, K. W. Jennette, S. H. Blobstein, I. B. Weinstein, F. A. Beland, R. G. Harvey, H. Kasai, I. Miura, and K. NakanishiCite this: J. Am. Chem. Soc. 1976, 98, 18, 5714–5715Publication Date (Print):September 1, 1976Publication History Published online1 May 2002Published inissue 1 September 1976https://pubs.acs.org/doi/10.1021/ja00434a060https://doi.org/10.1021/ja00434a060research-articleACS PublicationsRequest reuse permissionsArticle Views138Altmetric-Citations201LEARN 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
Methane monooxygenase from Methylosinus trichosporium OB3b (1989)

Methane monooxygenase has been purified from the Type II methanotroph Methylosinus trichosporium OB3b. As observed for methane monooxygenase isolated from Type I methanotrophs, three protein components are required: a 39.7-kDa NADH reductase containing 1 mol each of FAD and a [2Fe-2S] cluster, a 15.8-kDa protein factor termed component B that contains no metals or cofactors, and a 245-kDa hydroxylase which appears to contain an oxo- or hydroxo-bridged binuclear iron cluster. Through the use of stabilizing reagents, the hydroxylase is obtained in high yield and exhibits a specific activity 8-25-fold greater than reported for previous preparations. The component B and reductase exhibit 1.5- and 4-fold greater specific activity, respectively. Quantitation of the hydroxylase oxo-bridged cluster using EPR and Mössbauer spectroscopies reveals that the highest specific activity preparations (approximately 1700 nmol/min/mg) contain approximately 2 clusters/mol. In contrast, hydroxylase preparations exhibiting a wide range of specific activities below 500 nmol/min/mg contain approximately 1 cluster/mol on average. Efficient turnover coupled to NADH oxidation requires all three protein components. However, both alkanes and alkenes are hydroxylated by the chemically reduced hydroxylase under single turnover conditions in the absence of component B and the reductase. Neither of these components catalyzes hydroxylation individually nor do they significantly affect the yield of hydroxylated product from the chemically reduced hydroxylase. Hydroxylase reduced only to the mixed valent [Fe(II).Fe(III)] state is unreactive toward O2 and yields little hydroxylated product on single turnover. This suggests that the catalytically active species is the fully reduced form. The data presented here provide the first evidence based on catalysis that the site of the monooxygenation reaction is located on the hydroxylase. It thus appears likely that the oxo-bridged iron cluster is capable of catalyzing oxygenase reactions without the intervention of other cofactors. This is a novel function for this type of cluster and implies a new mechanism for the generation of highly reactive oxygen capable of insertion into unactivated carbon-hydrogen bonds.
Antimicrobial and Probiotic Properties of Yeasts: From Fundamental to Novel Applications (2012)

The yeasts constitute a large and heterogeneous group of microorganisms that are currently attracting increased attention from scientists and industry. Numerous and diverse biological activities make them promising candidates for a wide range of applications not limited to the food sector. In addition to their major contribution to flavor development in fermented foods, their antagonistic activities toward undesirable bacteria, and fungi are now widely known. These activities are associated with their competitiveness for nutrients, acidification of their growth medium, their tolerance of high concentrations of ethanol, and release of antimicrobial compounds such as antifungal killer toxins or "mycocins" and antibacterial compounds. While the design of foods containing probiotics (microorganisms that confer health benefits) has focused primarily on Lactobacillus and Bifidobacterium, the yeast Saccharomyces cerevisiae var. boulardii has long been known effective for treating gastroenteritis. In this review, the antimicrobial activities of yeasts are examined. Mechanisms underlying this antagonistic activity as well as recent applications of these biologically active yeasts in both the medical and veterinary sectors are described.