gebhart/patrepeval huggingface dataset:
Expression cloning of a gibberellin 20-oxidase, a multifunctional enzyme involved in gibberellin biosynthesis. (1994)

In the biosynthetic pathway to the gibberellins (GAs), carbon-20 is removed by oxidation to give the C19-GAs, which include the biologically active plant hormones. We report the isolation of a cDNA clone encoding a GA 20-oxidase [gibberellin, 2-oxoglutarate:oxygen oxidoreductase (20-hydroxylating, oxidizing) EC 1.14.11.-] by screening a cDNA library from developing cotyledons of pumpkin (Cucurbita maxima L.) for expression of this enzyme. When mRNA from either the cotyledons or the endosperm was translated in vitro using rabbit reticulocyte lysates, the products contained GA12 20-oxidase activity. A polyclonal antiserum was raised against the amino acid sequence of a peptide released by tryptic digestion of purified GA 20-oxidase from the endosperm. A cDNA expression library in lambda gt11 was prepared from cotyledon mRNA and screened with the antiserum. The identity of positive clones was confirmed by the demonstration of GA12 20-oxidase activity in single bacteriophage plaques. Recombinant protein from a selected clone catalyzed the three-step conversions of GA12 to GA25 and of GA53 to GA17, as well as the formation of the C19-GAs, GA1, GA9, and GA20, from their respective aldehyde precursors, GA23, GA24, and GA19. The nucleotide sequence of the cDNA insert contains an open reading frame of 1158 nt encoding a protein of 386 amino acid residues. The predicted M(r) (43,321) and pI (5.3) are similar to those determined experimentally for the native GA 20-oxidase. Furthermore, the derived amino acid sequence includes sequences obtained from the N terminus and two tryptic peptides from the native enzyme. It also contains regions that are highly conserved in a group of non-heme Fe-containing dioxygenases.
Demonstration of new sites of expression of the CCK-B/gastrin receptor in pancreatic acinar AR42J cells using immunoelectron microscopy (1999)

The CCK-B/gastrin receptor has been characterised in both normal and tumour tissues. Endocytosis of the CCK-B/gastrin receptor has recently been demonstrated and this has similarly been described for other peptide receptors. In addition, ligand and ligand-receptor translocation to the nucleus has been demonstrated for other peptides, The aim of this study was to identify the sites of expression of the CCK-B/gastrin receptor in the known CCK-B/gastrin receptor bearing pancreatic acinar AR42J cells. The specificity of the CCK-B/gastrin receptor antibody (alpha-CCKBR-Ser antibody) was demonstrated by inhibition ELISA studies, radioligand inhibition studies and immunofluorescence binding studies on AR42J cells. Western blotting and immunogold electron microscopy techniques were used to identify the receptor in AR42J cell preparations. The affinity purified alpha-CCKBR-Ser antibody was shown to be specific for the CCK-B/gastrin receptor. The receptor was expressed on the cell membrane, in the cytoplasm and within the nucleus. Isoforms of the receptor protein identified in extra-nuclear and nuclear extracts ranged in molecular weight from 58 to 66 kDa. We conclude that the CCK-B/gastrin receptor is not only expressed on the cell membrane, but also in the cytoplasm and nucleus of AR42J pancreatic acinar cells, (C) 1999 Elsevier Science B.V. All rights reserved.
Alteration of synaptic membrane cholesterol/phospholipid ratio using a lipid transfer protein. Effect on gamma-aminobutyric acid uptake. (1983)

A procedure was developed to vary the cholesterol-to-phospholipid (Ch/PL) ratio of synaptic plasma membranes and synaptosomes using a nonspecific lipid transfer protein so that membrane lipid composition could be correlated with presynaptic function. In synaptic plasma membranes, Ch/PL molar ratios from 0.21 to 1.19 were produced from a normal value of 0.52 +/- 0.01 by incubation with the transfer protein and an excess of either phosphatidylcholine or cholesterol/phosphatidylcholine liposomes for 60 min at 32 degrees C. In synaptosomes, Ch/PL ratios from 0.16 to 0.81 were similarly produced from a normal value of 0.38 +/- 0.04. Cholesterol loading or depletion of the membranes was accompanied by a decrease or increase, respectively in the phospholipid-to-protein ratio. The fluidity of the synaptic plasma membrane, as estimated by 1,6-diphenylhexatriene anisotropy measurements, was increased by lowering the Ch/PL ratio and decreased by raising the Ch/PL ratio. Decreasing the Ch/PL ratio of synaptosomes and synaptic plasma membrane vesicles resulted in loss of sodium-dependent gamma-aminobutyric acid (GABA) uptake (70-100% loss at Ch/PL ratios decreased to 40% of normal) and reduction in the number of accessible GABA-binding sites. Choline uptake was not affected in these same preparations. GABA uptake was restored by reinserting cholesterol into the membrane. Synaptosomal membrane potential and synaptic plasma membrane sodium permeability were not affected by changing the Ch/PL ratio. Increase in the Ch/PL ratio above normal had no effect on either choline or GABA uptake. Both the decrease in the Ch/PL ratio and the increase in the lipid-to-protein ratio increase membrane "fluidity," lipid-to-protein ratio increase membrane "fluidity," which may modulate the vertical displacement and motional characteristics of the GABA transporter.
Ruthenium catalyzed equilibrium ring-opening metathesis polymerization of cyclopentene (2013)

Polypentenamer was synthetized by equilibrium ring-opening metathesis polymerization (ROMP) using well-defined ruthenium catalyst systems. It was found that the equilibrium time is influenced by the catalyst loading or the catalyst activity, however as expected, the overall cyclopentene conversion is determined only by the applied reaction temperature. Equilibrium of the growing chain and monomer was observed and the activation enthalpy and entropy were determined as: ΔH = −5.6 kcal mol−1; ΔS = −18.5 cal mol−1 K−1. So far these values are the lowest which are reported for cyclopentene polymerization catalyst systems. This unique feature of the equilibrium polymerization opens a way for the synthesis of durable, environmentally friendly elastomers where tires can be not only synthetized but also readily recycled by the same transition metal catalyst system.
Scavenging of hydroxyl radicals but not of peroxynitrite by inhibitors and substrates of nitric oxide synthases (1997)

1. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) is widely used to study the role of NO. in physiological and pathological processes, including its role in the generation of the cytotoxic species peroxynitrite (ONOO-) and of reactive oxygen radicals such as hydroxyl (OH.). Often L-NAME is applied to tissues at mM concentrations. At such high concentrations, it might act as a free radical scavenger. A similar possibility might apply to the use of high levels of arginine to study the role of NO. in atherogenesis. 2. We therefore examined the rate of scavenging of OH. by L-NAME and found that L-NAME reacts more quickly with OH. than the established 'OH. scavenger' mannitol and the widely used 'OH. trap' salicylate. However, D-NAME can scavenge OH. at rates equal to L-NAME. Both L- and D-arginine were also good OH. scavengers, comparable in effectiveness to mannitol. 3. Neither L-NAME, D-NAME, L-arginine nor D-arginine was able to inhibit ONOO(-)-dependent nitration of tyrosine, suggesting that they are unlikely to be scavengers of ONOO(-)-derived nitrating species. 4. Neither L-NAME, D-NAME, L-arginine nor D-arginine was able to inhibit the inactivation of alpha 1-antiproteinase by ONOO-, suggesting that they cannot prevent direct oxidations by peroxynitrite. 5. We conclude that L-NAME has sufficient activity as an OH. scavenger to confound certain pharmacological experiments. However, this explanation of its biological effects can be ruled out if control experiments show that D-NAME has no effect and that L-arginine (also a free radical scavenger) antagonizes the action of L-NAME.
The P2-Na2/3Co2/3Mn1/3O2 phase: structure, physical properties and electrochemical behavior as positive electrode in sodium battery (2011)

Manganese substituted sodium cobaltate, Na(2/3)Co(2/3)Mn(1/3)O(2), with a layered hexagonal structure (P2-type) was obtained by a co-precipitation method followed by a heat treatment at 950 °C. Powder X-ray diffraction analysis revealed that the phase is pure in the absence of long-range ordering of Co and Mn ions in the slab or Na(+) and vacancy in the interslab space. The oxidation states of the transition metal ions were studied by magnetic susceptibility measurements, electron paramagnetic resonance (ESR) and (23)Na magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. The charge compensation is achieved by the stabilization of low-spin Co(3+) and Mn(4+) ions. The capability of Na(2/3)Co(2/3)Mn(1/3)O(2) to intercalate and deintercalate Na(+) reversibly was tested in electrochemical sodium cells. It appears that the P2 structure is maintained during cycling, the cell parameter evolution versus the sodium amount is given. From the features of the cycling curve the formation of an ordered phase for the Na(0.5)Co(2/3)Mn(1/3)O(2) composition is expected.
Prevention of SIV Infection in Macaques by ( R )-9-(2-Phosphonylmethoxypropyl)adenine (1995)

The efficacy of pre- and postexposure treatment with the antiviral compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian immunodeficiency virus (SIV) in macaques as a model for human immunodeficiency virus (HIV). PMPA was administered subcutaneously once daily beginning either 48 hours before, 4 hours after, or 24 hours after virus inoculation. Treatment continued for 4 weeks and the virologic, immunologic, and clinical status of the macaques was monitored for up to 56 weeks. PMPA prevented SIV infection in all macaques without toxicity, whereas all control macaques became infected. These results suggest a potential role for PMPA prophylaxis against early HIV infection in cases of known exposure.
Isolation of human Dna2 endonuclease and characterization of its enzymatic properties (2006)

In eukaryotes, the creation of ligatable nicks in DNA from flap structures generated by DNA polymerase delta-catalyzed displacement DNA synthesis during Okazaki fragment processing depends on the combined action of Fen1 and Dna2. These two enzymes contain partially overlapping but distinct endonuclease activities. Dna2 is well-suited to process long flaps, which are converted to nicks by the subsequent action of Fen1. In this report, we purified human Dna2 as a recombinant protein from human cells transfected with the cDNA of the human homologue of Saccharomyces cerevisiae Dna2. We demonstrated that the purified human Dna2 enzyme contains intrinsic endonuclease and DNA-dependent ATPase activities, but is devoid of detectable DNA helicase activity. We determined a number of enzymatic properties of human Dna2 including its substrate specificity. When both 5' and 3' tailed ssDNAs were present in a substrate, such as a forked-structured one, both single-stranded regions were cleaved by human Dna2 (hDna2) with equal efficiency. Based on this and other properties of hDna2, it is likely that this enzyme facilitates the removal of 5' and 3' regions in equilibrating flaps that are likely to arise during the processing of Okazaki fragments in human cells.
Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: A systematic review and meta-analysis (2016)

Our results suggest that MF59-TIV is effective in reducing several influenza-related outcomes among the elderly, especially hospitalizations due to influenza-related complications.
Using Matrix and Tensor Factorizations for the Single-Trial Analysis of Population Spike Trains (2016)

Advances in neuronal recording techniques are leading to ever larger numbers of simultaneously monitored neurons. This poses the important analytical challenge of how to capture compactly all sensory information that neural population codes carry in their spatial dimension (differences in stimulus tuning across neurons at different locations), in their temporal dimension (temporal neural response variations), or in their combination (temporally coordinated neural population firing). Here we investigate the utility of tensor factorizations of population spike trains along space and time. These factorizations decompose a dataset of single-trial population spike trains into spatial firing patterns (combinations of neurons firing together), temporal firing patterns (temporal activation of these groups of neurons) and trial-dependent activation coefficients (strength of recruitment of such neural patterns on each trial). We validated various factorization methods on simulated data and on populations of ganglion cells simultaneously recorded in the salamander retina. We found that single-trial tensor space-by-time decompositions provided low-dimensional data-robust representations of spike trains that capture efficiently both their spatial and temporal information about sensory stimuli. Tensor decompositions with orthogonality constraints were the most efficient in extracting sensory information, whereas non-negative tensor decompositions worked well even on non-independent and overlapping spike patterns, and retrieved informative firing patterns expressed by the same population in response to novel stimuli. Our method showed that populations of retinal ganglion cells carried information in their spike timing on the ten-milliseconds-scale about spatial details of natural images. This information could not be recovered from the spike counts of these cells. First-spike latencies carried the majority of information provided by the whole spike train about fine-scale image features, and supplied almost as much information about coarse natural image features as firing rates. Together, these results highlight the importance of spike timing, and particularly of first-spike latencies, in retinal coding.
Stat3 Activation by Src Induces Specific Gene Regulation and Is Required for Cell Transformation (1998)

While signal transducers and activators of transcription (STATs) were originally discovered as intracellular effectors of normal signaling by cytokines, increasing evidence also points to a role for STAT transcription factors in oncogenesis. Previous studies have demonstrated that one STAT family member, Stat3, possesses constitutively elevated tyrosine phosphorylation and DNA-binding activity in fibroblasts stably transformed by the Src oncoprotein. To determine if this Stat3 activation by Src could induce Stat3-mediated gene expression, luciferase reporter constructs based on synthetic and authentic promoters were transfected into NIH 3T3 cells. Activation of endogenous cellular Stat3 by the Src oncoprotein induced gene expression through a Stat3-specific binding element (TTCCCGAA) of the C-reactive protein gene promoter. A naturally occurring splice variant of human Stat3 protein, Stat3beta, with a deletion in the C-terminal transactivation domain abolished this gene induction in a dominant negative manner. Expression of Stat3beta did not have any effect on a reporter construct based on the c-fos serum response element, which is not dependent on Stat3 signaling, indicating that Stat3beta does not nonspecifically inhibit other signaling pathways or Src function. Transfection of vectors expressing Stat3beta together with Src blocked cell transformation by Src as measured in a quantitative focus formation assay using NIH 3T3 cells. By contrast, Stat3beta had a much less pronounced effect on focus formation induced by the Ras oncoprotein, which does not activate Stat3 signaling. In addition, three independent clones of NIH 3T3 cells stably overexpressing Stat3beta were generated and characterized, demonstrating that Stat3beta overexpression does not have a toxic effect on cell viability. These Stat3beta-overexpressing clones were shown to be deficient in Stat3-mediated signaling and refractory to Src-induced cell transformation. We conclude that Stat3 activation by the Src oncoprotein leads to specific gene regulation and that Stat3 is one of the critical signaling pathways involved in Src oncogenesis. Our findings provide evidence that oncogenesis-associated activation of Stat3 signaling is part of the process of malignant transformation.
Functional evolutionary history of the mouse Fgf gene family (2007)

Fibroblast Growth Factors (FGFs) are polypeptides with diverse activities in development and physiology. The mammalian Fgf family can be divided into the intracellular Fgf11/12/13/14 subfamily (iFGFs), the hormone-like Fgf15/21/23 subfamily (hFGFs), and the canonical Fgf subfamilies, including Fgf1/2/5, Fgf3/4/6, Fgf7/10/22, Fgf8/17/18, and Fgf9/16/20. However, all Fgfs are evolutionarily related. We propose that an Fgf13-like gene is the ancestor of the iFgf subfamily and the most likely evolutionary ancestor of the entire Fgf family. Potential ancestors of the canonical and hFgf subfamilies, Fgf4-, Fgf5-, Fgf8-, Fgf9-, Fgf10-, and Fgf15-like, appear to have derived from an Fgf13-like ancestral gene. Canonical FGFs function in a paracrine manner, while hFGFs function in an endocrine manner. We conclude that the ancestral Fgfs for these subfamilies acquired this functional diversity before the evolution of vertebrates. During the evolution of early vertebrates, the Fgf subfamilies further expanded to contain three or four members in each subfamily.
Nanobody; an Old Concept and New Vehicle for Immunotargeting (2011)

The use of antibodies in cancer therapy has come a long way since the day Paul Ehrlich described the concept and Kohler and Milstein devised the hybridoma technology to bring this theory to reality. The synthesis of murine monoclonal antibodies (mAbs) was the first success in this field, leading to the invention of chimerization, the production of variable fragments (Fv) with the progression to domain antibodies (dAb) and later humanization technologies to maximize the clinical utility of murine mAbs. It was just by chance that dAbs were found to exist in ?heavy chain? immunoglobulins from Camelidae family and cartilaginous fish. These unique antibody fragments interact with antigen by virtue of only one single variable domain, referred to as VHH or nanobody. Several characteristics make nanobody use superior to the abovementioned antibodies. They are non-immunogenic and show high thermal and chemical stability. There are several reports of raising specific nanobodies against enzymes, haptens, pathogens, toxins and tumor markers, which are outlined in this paper. All these characteristics make them strong candidates as targeting agents for cancer therapy.
Chemical genetics approach to hepatitis C virus replication: cyclophilin as a target for anti‐hepatitis C virus strategy (2007)

Hepatitis C virus (HCV) is a major causative agent of liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Because the current standard therapy, interferon (IFN) or pegylated-IFN alone or in combination with ribavirin, is ineffective on approximately half of the HCV-infected patients, alternative therapeutics are greatly needed. The chemical genetics method is a useful strategy to elucidate molecular mechanisms of the viral life cycle and screen for anti-viral agents. This review focuses on the use of chemical genetics approach to virology, which could be called 'chemical virology', and introduces an example of such analysis. From a cell culture-based screening, an immunosuppressant cyclosporin A (CsA) was identified as an anti-HCV compound. Analysis using CsA as a bioprobe showed that cyclophilin (CyP) B, a cellular target of CsA, regulates the function of HCV RNA polymerase NS5B, which is essential for efficient viral genome replication. By targeting CyP, HCV genome replication was drastically suppressed. Thus, chemical genetics analysis identified CyPB as a cellular cofactor of HCV genome replication and a target for novel anti-HCV agents.
Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells (2003)

In liver development, a number of growth factors (GFs) and components of the extracellular matrix (ECMs) lead to differentiation of liver parenchymal cells. As the liver contains many cell types, specifically investigating their functional effects on hepatic stem cell populations is difficult. Prospective isolation and clonal assays for hepatic stem cells enable the examination of direct effects of GFs and ECMs on this rare cell fraction. Using previously purified cells that fulfill the criteria for hepatic stem cells, we examined how GFs and ECMs regulate differentiation in the developing liver. We show here that hepatocyte growth factor (HGF) induced early transition of albumin (ALB)-negative stem cells to ALB-positive hepatic precursors resembling hepatoblasts and then oncostatin M (OSM) promoted their differentiation to tryptophan-2, 3-dioxygenase (TO)-positive mature hepatocytes. During this transition, ECMs were necessary for the differentiation of stem cells and precursors, but their effects were only supportive. In the first step of stem cell differentiation induced by HGF, the expression of CCAAT/enhancer binding protein (C/EBP), a basic leucine zipper transcription factor, changed dramatically. When C/EBP function was inhibited in stem cells, they stopped differentiating to hepatocyte-lineage cells and proliferated actively. These are the first findings to illustrate the mechanism of hepatic stem cell differentiation in liver development.
Exploring the synergy between entrepreneurship and innovation (2005)

Purpose To contribute to an understanding of the complementary nature of entrepreneurship and innovation through an empirical study of various organisations; and to develop an integrative framework of the interaction between entrepreneurship and innovation. Design/methodology/approach The study takes a qualitative approach in exploring the synergies between entrepreneurship and innovation and in analysing the factors that foster an interaction between the two. Case studies of six entrepreneurial and innovative organisations and in‐depth interviews with senior managers were conducted to complement a comprehensive literature review of entrepreneurship and innovation. Findings The study has found that: entrepreneurship and innovation are positively related to each other and interact to help an organisation to flourish; entrepreneurship and innovation are complementary, and a combination of the two is vital to organisational success and sustainability in today's dynamic and changing environment; entrepreneurship and innovation are not confined to the initial stages of a new venture; rather, they are dynamic and holistic processes in entrepreneurial and innovative organisations; and organisational culture and management style are crucial factors affecting the development of entrepreneurial and innovation behaviour in organisations. Originality/value Entrepreneurship and innovation should be regarded as ongoing, everyday practice in organisations, and this paper has contributed to the development of such an attitude.This empirical study contributes to an understanding of the existing theories and practices of entrepreneurship and innovation in organisations.