gebhart/patrepeval huggingface dataset:
Isolation and preliminary characterization of a monoclonal antibody that interacts preferentially with the liver isoenzyme of human alkaline phosphatase. (1985)

We have prepared murine monoclonal antibodies against isolated human bone alkaline phosphatase (ALP, EC 3.1.3.1). Hybridoma supernates were separately screened for reactivity against both human liver and bone ALP. Although most antibody-positive hybrids showed similar reactivity against both isoenzymes, one hybridoma produced an antibody that interacted preferentially with liver ALP. This antibody was purified and used to establish an immunoassay to differentiate liver ALP from bone ALP. When equal activities of the two isoenzymes (as determined by a conventional enzymic assay) were measured by the immunoassay, a fivefold greater response was obtained with liver than with bone ALP. The immunoassay can be used to measure the proportions of the bone and liver isoenzymes in mixtures of them. Cross reactivity with human placental and intestinal ALP is less than 3% relative to liver ALP. These findings support the feasibility of developing immunological methods to differentiate these isoenzymes in the clinical laboratory.
Modulation of glucagon receptor expression and response in transfected human embryonic kidney cells (2001)

The modulation of glucagon receptor (GR) expression and biological response was investigated in human embryonic kidney cell (HEK-293) clones permanently expressing the GR with different densities. The GR mRNA expression level in these clones was upregulated by cellular cAMP accumulation and presented a good correlation with both the protein expression level and the maximum number of glucagon binding sites. However, the determination of glucagon-induced cAMP accumulation in these cell lines revealed that the enhancement of receptor expression did not lead to a proportional increase in cAMP formation. Under these conditions, the maximum cAMP production induced by NaF and forskolin was not significantly different among selected clones, regardless of the receptor expression level. High receptor-expressing clones showed the greatest susceptibility for agonist-induced desensitization compared with clones with lower GR expression levels. The results of the present study suggest that the GR can recruit non-GR-specific desensitization mechanism(s). Furthermore, the partial inhibition or alteration of the overall cAMP synthesis pathway at the receptor level may be a necessary adaptive step for a cell in response to a massive increase in membrane receptor expression level.
Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation. (1990)

To study the mechanism of regression of human prostatic cancer following androgen ablation, the androgen-responsive PC-82 human prostatic adenocarcinoma xenograft was used as a model system. Castration of male nude mice bearing PC-82 xenografts results in a 50% tumor regression by 2 wk following androgen ablation. This regression is due to a sequence of biochemical and morphological events that results in both the cessation of cell proliferation and activation of programmed death or apoptosis of the androgen-dependent prostatic cancer cells. Associated with this response are an enhanced expression of the transforming growth factor beta 1 gene, a potent inhibitor of cell proliferation, and testosterone-repressed prostatic message 2 (designated TRPM-2), a programmed cell death-associated gene. Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that preceded the dramatic reduction in tumor volume following androgen ablation. These results suggest that androgen-dependent human prostatic cancer cells, like normal prostatic cells, retain the ability to inhibit proliferation and to activate programmed cell death in response to androgen ablation. Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even androgen-independent human prostatic cancer.
Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia [published erratum appears in Blood 1989 Aug 15;74(3):1180] (1989)

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.
c-di-GMP Displays A Monovalent Metal Ion-Dependent Polymorphism (2004)

Cyclic diguanosine monophosphate (c-di-GMP) is known to be an important signaling molecule that regulates the formation of bacterial biofilms. We demonstrate here by UV, CD, and NMR that it displays a surprising polymorphism that varies with the monovalent counterion and is consistent with the formation of a G-quartet structure in K+ and a stacked structure in Li+ or Na+. The ability of this rigid molecule to adopt different alignments may be important to its biological role.
Non-replicating Epstein-Barr Virus-based Plasmids Extend Gene Expression and Can Improve Gene Therapy in Vivo (2000)

To date, no gene transfer vector has produced prolonged gene expression following a single intravenous injection and then efficiently re-expressed the delivered gene following repeated systemic injection into immunocompetent hosts. To overcome these limitations, a gene therapy regimen using non-replicating Epstein-Barr virus (EBV)-based expression plasmids was developed. One plasmid contains the FR (EBV family of repeats) sequence and the expressed gene. The other encodes Epstein-Barr nuclear antigen 1 (EBNA-1), but lacks FR. Although unable to replicate in mice, intravenous co-injection of EBV-based plasmids in cationic liposome-DNA complexes (CLDCs) substantially prolonged luciferase gene expression. The use of a two-vector system limited host exposure to the EBNA-1 gene product. Furthermore, this EBV-based vector system could be intravenously re-injected multiple times into immunocompetent mice without loss of transfection efficiency. Use of this vector system significantly improved the therapeutic efficacy of the biologically important human granulocyte colony-stimulating factor gene. Delivery of the human granulocyte colony-stimulating factor gene in EBV-based plasmids increased circulating white blood counts for at least 2 months following a single CLDC-based intravenous co-injection. Conversely, white blood counts were never elevated following injection of CLDCs lacking EBV-derived elements. Thus, this EBV-based plasmid vector system both markedly prolongs gene expression at therapeutic levels and efficiently and repeatedly re-transfects immunocompetent hosts. These properties of EBV-based plasmid vectors appear to be due, at least in part, to the documented abilities of the EBNA-1 protein both to retain FR-containing DNA intracellularly and within the nucleus and to block anti-EBNA-1 cytotoxic T cell responses.
Steady-State Kinetics and Tryptophan Fluorescence Properties of Halohydrin Dehalogenase from Agrobacterium radiobacter. Roles of W139 and W249 in the Active Site and Halide-Induced Conformational Change (2003)

Halohydrin dehalogenase (HheC) from Agrobacterium radiobacter AD1 is a homotetrameric protein containing four tryptophan residues per subunit. The fluorescence properties of the enzyme are strongly influenced by halide binding. To examine the role of the tryptophans (W139, W192, W238, and W249) in halide binding and catalysis, they were individually mutated to a phenylalanine. All mutations, except for W238F, influenced the enzymatic properties. Mutating W192 to phenylalanine inactivated the enzyme and led to dissociation into dimers and monomers. In the structure of HheC, residue W139 and residue W249 from the opposite subunit are close to the active site of the enzyme. Substitution of W139 mainly affected K(m) values with all tested substrates and reduced the enantiopreference for p-nitro-2-bromo-1-phenylethanol. Replacing W249 increased both k(cat) and K(m) values with all tested substrates except for the (S)-enantiomer of p-nitro-2-bromo-1-phenylethanol, for which k(cat) was 3-fold decreased, resulting in a 6-fold increase of the enantioselectivity. Fluorescence measurements revealed that in the ligand-free state the intrinsic protein fluorescence of mutant W139F is higher than that of the wild-type enzyme, while the fluorescence intensity of mutants W238F and W249F was lower. The fluorescence intensities of the W238F and W249F enzymes were increased when they were unfolded or when bromide was added, whereas the fluorescence of mutant W139F was not increased by unfolding or addition of bromide. These results demonstrate that the fluorescence of residues W238 and W249 is partially quenched in the folded ligand-free state, and that W139 is completely quenched and acts as an energy acceptor for the other tryptophan residues as well. Changes of the maximum fluorescence emission wavelength of the HheC variants and the results of acrylamide quenching experiments confirmed that bromide binding induces a local conformational change around the active site, resulting in residue W139 and the quencher group being separated.
Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma (2005)

Increased intraocular pressure (IOP) leads, by an unknown mechanism, to apoptotic retinal ganglion cell (RGC) death in glaucoma. We now report cleavage of the autoinhibitory domain of the protein phosphatase calcineurin (CaN) in two rodent models of increased IOP. Cleaved CaN was not detected in rat or mouse eyes with normal IOP. In in vitro systems, this constitutively active cleaved form of CaN has been reported to lead to apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member, Bad. In a rat model of glaucoma, we similarly detect increased Bad dephosphorylation, increased cytoplasmic cytochrome c (cyt c), and RGC death. Oral treatment of rats with increased IOP with the CaN inhibitor FK506 led to a reduction in Bad dephosphorylation and cyt c release. In accord with these biochemical results, we observed a marked increase in both RGC survival and optic nerve preservation. These data are consistent with a CaN-mediated mechanism of increased IOP toxicity. CaN cleavage was not observed at any time after optic nerve crush, suggesting that axon damage alone is insufficient to trigger cleavage. These findings implicate this mechanism of CaN activation in a chronic neurodegenerative disease. These data demonstrate that increased IOP leads to the initiation of a CaN-mediated mitochondrial apoptotic pathway in glaucoma and support neuroprotective strategies for this blinding disease.
Mechanism of Action of EM 49, Membrane-Active Peptide Antibiotic (1977)

EM 49 (recently renamed octapeptin) is a membrane-active peptide antibiotic that has been reported to affect the structure of bacterial membranes (K. S. Rosenthal, P. E. Swanson, and D. R. Storm, Biochemistry 15:5783-5792, 1976). In this study, it is shown that the effects of EM 49 on bacterial metabolism are similar to those of uncouplers of oxidative phosphorylation. EM 49 stimulated bacterial respiration within a narrow concentration range corresponding to minimum inhibitory concentrations and inhibited respiration at concentrations comparable to minimum biocidal concentrations. In addition, the peptide increased membrane proton permeability and lowered the adenosine 5'-triphosphate pool size. Parallel studies done with the related antibiotic polymyxin B demonstrated that the two peptides differed considerably in their effects on bacterial respiration. In contrast to EM 49, polymyxin B did not stimulate respiration at any concentration. It is proposed that the primary action of EM 49 is to disrupt the selective ion permeability of the cytoplasmic membrane, thereby relaxing the membrane potential.
Improved conversion of fumarate to succinate by Escherichia coli strains amplified for fumarate reductase (1983)

Two recombinant plasmid Escherichia coli strains containing amplified fumarate reductase activity converted fumarate to succinate at significantly higher rates and yields than a wild-type E. coli strain. Glucose was required for the conversion of fumarate to succinate, and in the absence of glucose or in cultures with a low cell density, malate accumulated. Two-dimensional gel electrophoretic analysis of proteins from the recombinant DNA and wild-type strains showed that increased quantities of both large and small fumarate reductase subunits were expressed in the recombinant DNA strains.
Genetic Engineering of Novel Genomes of Large DNA Viruses (1985)

Analyses of the function of specific genes and sequences of large DNA viruses such as herpesviruses and poxviruses present special problems because of the size of their genomes (120 to 250 kilobase pairs). Various methods for engineering site-specific insertions or deletions based on the use of selectable markers have been developed and applied for the elucidation of the function of specific DNA sequences, the identification of genes nonessential for virus growth in cell culture, and the expression of foreign genes. These methods should also make possible the construction of viral vectors capable of delivering genes specifying antigens for the prevention of infectious diseases in humans and animals.
Implementation of both high-hole and electron mobility in strained Si/strained Si<sub>1-y</sub>Ge<sub>y</sub> on relaxed Si<sub>1-x</sub>Ge<sub>x</sub> (x<y) virtual substrate (2003)

High-hole and electron mobility in complementary channels in strained silicon (Si) on top of strained Si/sub 0.4/Ge/sub 0.6/, both grown on a relaxed Si/sub 0.7/Ge/sub 0.3/ virtual substrate is shown for the first time. The buried Si/sub 0.4/Ge/sub 0.6/ serves as a high-mobility p-channel, and the strained-Si cap serves as a high-mobility n-channel. The effective mobility, measured in devices with a 20-&#x003BC;m gate length and 3.8-nm gate oxide, shows about 2.2/spl sim/2.5 and 2.0 times enhancement in hole and electron mobility, respectively, across a wide vertical field range. In addition, it is found that as the Si cap thickness decreased, PMOS transistors exhibited increased mobility especially at medium- and high-hole density in this heterostructure.
Organic and Hybrid-perovskite Photovoltaic Cells with High Performance (2014)

Solution-processed organic solar cells and organic-inorganic hybrid solar cells are among the most promising photovoltaic technologies for ultimatelow-costmanufacture. In this presentation, I will brie∞y report our recent works: small molecule, polymer and perovskite photovoltaics. (1) Small molecule OPV. Small molecule organic semiconductors have attracted increasing in- terest due to the advantages of its well-deflned structures, facile synthesis and puriflcation, and generally high charge carrier mobility. In the flrst part of my presentation, I will report high performance single junction and double junction OPV device based on DOR3T-BDTT. Using the solution spin-coating fabrication process, the certifled power conversion e-ciency (PCE) of 8.02% from single junction device was obtained. A homo-tandem solar cell was constructed with a novel solution processed interlayer (or tunnel junction), demonstrating an unprecedented PCE of 10.1%. (2) The second part of my presentation is on polymer solar cell. Recently, we demonstrate two families of NIR conjugated polymers (Eg » 1:4eV) speciflcally suitable for tandem structure. One is based on alternating benzodithiophene/diketopyrrolopyrrole units and the other is based on alternating dithienopyran/di∞ourobenzothiadiazole units. In the single-layer devices, power conversion e-ciencies (PCE) of 7 » 8% were achieved. When the polymers were applied to tandem solar cells, we demonstrated PCE of 10.6% (under the AM 1.5G solar condition). Fur- thermore, the tandem devices show excellent stability due both to the intrinsic stability of the polymer and the advanced device structure. (3) The third part of my presentation is on the organic-inorganic hybrid perovskite based so- lar cells, particularly CH3NH3PbX3 (X = Cl, Br, I). We demonstrate a novel low tempera- ture vapor assisted solution process to fabricate organic-inorganic hybrid perovskite fllms (e.g., CH3NH3PbX3, X = Cl, Br, I) and the corresponding photovoltaic devices. The perovskite fllms derived from this approach exhibit superior fllm quality, with full surface coverage, uniform grain structure with grain size up to micron scale, and a complete precursor transformation. Facil- itated by the excellent fllm quality, the CH3NH3PbI3 materials enable a PCE over 12% in a planar architecture. We have further improved device engineering, and our latest perovksite so- lar cell has reached the best e-ciencies in the range of 15{19% 1 . We believe by further research in fllm formation, better device architecture, and interface engineering will lead to continuous improvement of perovskite solar cells.
Refinement of Eco RI Endonuclease Crystal Structure: A Revised Protein Chain Tracing (1990)

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Stimuli-Responsive Metal–Ligand Assemblies (2015)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTStimuli-Responsive Metal–Ligand AssembliesAnna J. McConnell, Christopher S. Wood, Prakash P. Neelakandan, and Jonathan R. Nitschke*View Author Information Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom*Tel.: +44 1223 336324. E-mail: [email protected]Cite this: Chem. Rev. 2015, 115, 15, 7729–7793Publication Date (Web):April 16, 2015Publication History Received1 November 2014Published online16 April 2015Published inissue 12 August 2015https://pubs.acs.org/doi/10.1021/cr500632fhttps://doi.org/10.1021/cr500632freview-articleACS PublicationsCopyright © 2015 American Chemical SocietyRequest reuse permissionsArticle Views20165Altmetric-Citations872LEARN 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:Ions,Ligands,Macrocycles,Metals,Pyrroles Get e-Alerts
Nuclear matrix proteins distinguish normal diploid osteoblasts from osteosarcoma cells. (1994)

Interrelationships between nuclear architecture and gene expression were examined by comparing the representation of nuclear matrix proteins in ROS 17/2.8 rat and MG-63 human osteosarcoma cells with those in normal diploid osteoblasts. The tumor-derived cells coexpress genes which are expressed in a sequential and mutually exclusive manner during the progressive stages of osteoblast differentiation. In osteosarcoma cells two-dimensional electrophoretic analysis indicates a composite representation of nuclear matrix proteins characteristic of both the proliferative and postproliferative periods of osteoblast phenotype development. In addition, nuclear matrix proteins unique to the tumor cells and the absence of nuclear matrix proteins found only in normal diploid osteoblasts are observed. Tumor-specific nuclear matrix proteins include those expressed in a proliferation-dependent and independent manner. There is a parallel relationship between nuclear matrix proteins and the expression of cell growth and tissue-specific genes during osteoblast differentiation and in osteosarcoma cells where the developmental sequence of gene expression has been abrogated. Nuclear matrix proteins therefore provide markers reflecting defined periods of bone cell differentiation and phenotypic characteristics of an osteosarcoma.
Aurelio Prudencio y el debate sobre el altar de la Victoria (2002)

El articulo presenta los argumentos del famoso debate sobre el altar de la Victoria del Senado Romano, que tuvo lugar el ano 384 entre el presidente del Senado Simaco, que defendia restaurar su culto, y el obispo de Milan Ambrosio que lo rechazaba. Veinte anos mas tarde el hispano de Calahorra Aurelio Prudencio, alto funcionario del Imperio ya jubilado, recoge el tema y expone en versos didacticos los argumentos de Ambrosio para reforzar la fe de los cristianos, que necesitaban razones. Rechaza el relativismo religioso, pero defiende el respeto a la cultura y a las obras de arte y la no discriminacion por motivos religiosos. Con una vision mas optimista que la de Ambrosio, afirma que el cristianismo es la plenitud de todo lo anterior, que Roma, haciendose cristiana, alcanza su destino eterno y que la fe crea cultura. Los temas que se abordan son de interes para el actual debate sobre el dialogo interreligioso y el papel de la religion en la sociedad