gebhart/patrepeval huggingface dataset:
Isolation and Characterization of S-Adenosylmethionine-requiring Mutants and Role of S-Adenosylmethionine in the Regulation of Methionine Biosynthesis inCorynebacterium glutamicum (1975)

Using a minimal medium containing a methionine analog together with a small amount of S-adenosylmethionine (SAM), many SAM requiring mutants which responded only to SAM and not to methionine, S-adenosylhomocysteine, or homocysteine were efficiently isolated from Corynebacterium glutamicum TLD-140 after mutagenesis. Among them, SAM-14 and SAM-19 selected from selenomethionine resistant mutants were subjected to further investigation. Both mutants were unable to grow in a minimal medium and had no detectable activity of SAM synthetase. Both mutants acquired higher resistance to methionine hydroxamate and ethionine as well as to selenomethionine than TLD-140 and produced l-methionine in a medium. Homoserine-O-transacetylase in SAM-19 was subject to full repression by the addition of excess SAM to the growth medium and was not repressed under SAM limitation, whereas addition of excess l-methionine under SAM limitation caused a partial repression of the enzyme. SAM synthetase as well as l-methionine biosynthetic enzymes in a methionine auxotroph of C. glutamicum was repressed by the addition of l-methionine to the growth medium. These results suggest that SAM is implicated in the repression of l-methionine synthesizing enzymes in C. glutamicum.
Lysosomal enzyme phosphorylation. II. Protein recognition determinants in either lobe of procathepsin D are sufficient for phosphorylation of both the amino and carboxyl lobe oligosaccharides (1992)

Cathepsin D is a bilobed lysosomal aspartyl protease that contains one Asn-linked oligosaccharide/lobe. Each lobe also contains protein determinants that serve as recognition domains for binding of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, the first enzyme in the biosynthesis of the mannose 6-phosphate residues on lysosomal enzymes. In this study we examined whether the location of the protein recognition domain influences the relative phosphorylation of the amino and carboxyl lobe oligosaccharides. To do this, chimeric proteins containing either amino or carboxyl lobe sequences of cathepsin D substituted into a glycosylated form of the homologous secretory protein pepsinogen were expressed in Xenopus oocytes. The amino and carboxyl lobe oligosaccharides were then isolated from the various chimeric proteins and independently analyzed for their mannose 6-phosphate content. This analysis has shown that a phosphotransferase recognition domain located on either lobe of a cathepsin D/glycopepsinogen chimeric molecule is sufficient to allow phosphorylation of oligosaccharides on both lobes. However, phosphorylation of the oligosaccharide on the lobe containing the recognition domain is favored. We also found that the majority of the carboxyl lobe oligosaccharides of cathepsin D acquire two phosphates, whereas the amino lobe oligosaccharides only acquire one phosphate.
The von Hippel-Lindau Tumor Suppressor Gene Product Interacts with Sp1 To Repress Vascular Endothelial Growth Factor Promoter Activity (1997)

The von Hippel-Lindau tumor suppressor gene (VHL) has a critical role in the pathogenesis of clear-cell renal cell carcinoma (RCC), as VHL mutations have been found in both von Hippel-Lindau disease-associated and sporadic RCCs. Recent studies suggest that vascular endothelial growth factor (VEGF) mRNA is upregulated in RCC- and von Hippel-Lindau disease-associated tumors. We have therefore assessed the effect of the VHL gene product on VEGF expression. VEGF promoter-luciferase constructs were transiently cotransfected with a wild-type VHL (wt-VHL) vector in several cell lines, including 293 embryonic kidney and RCC cell lines. wt-VHL protein inhibited VEGF promoter activity in a dose-dependent manner up to 5- to 10-fold. Deletion analysis defined a 144-bp region of the VEGF promoter necessary for VHL repression. This VHL-responsive element is GC rich and specifically binds the transcription factor Sp1 in crude nuclear extracts. In Drosophila cells, cotransfected VHL represses Sp1-mediated activation but not basal activity of the VEGF promoter. We next demonstrated in coimmunoprecipitates that VHL and Sp1 were part of the same complex and, by using a glutathione-S-transferase-VHL fusion protein and purified Sp1, that VHL and Sp1 directly interact. Furthermore, endogenous VEGF mRNA levels were suppressed in permanent RCC cell lines expressing wt-VHL, and nuclear run-on studies indicated that VHL regulation of VEGF occurs at least partly at the transcriptional level. These observations support a new mechanism for VHL-mediated transcriptional repression via a direct inhibitory action on Sp1 and suggest that loss of Sp1 inhibition may be important in the pathogenesis of von Hippel-Lindau disease and RCC.
Synthesis and Serotonergic Activity of 3-[2-(Pyrrolidin-1-yl)ethyl]indoles:  Potent Agonists for the h5-HT1D Receptor with High Selectivity over the h5-HT1B Receptor (1999)

The design, synthesis, and biological evaluation of a novel series of 3-[2-(pyrrolidin-1-yl)ethyl]indoles with excellent selectivity for h5-HT1D (formerly 5-HT1Dalpha) receptors over h5-HT1B (formerly 5-HT1Dbeta) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT1D and h5-HT1B receptors. The differential expression of h5-HT1D and h5-HT1B receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT1D subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT1D over h5-HT1B receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT1D receptor and 100-fold selectivity with respect to h5-HT1B receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT1D subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPgammaS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT1D and h5-HT1B receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT1D receptor domain which is absent for the h5-HT1B receptor. The compounds described herein will be important tools to delineate the role of h5-HT1D receptors in migraine.
Defect models of the low and high temperature centres of Cr3+ in alpha-LiIO3 : Cr3+ crystals (1999)

By analysing the EPR spectra of alpha-LiIO3:Cr3+ the defect models of a low temperature centre Cr3+L and two high temperature centres Cr3+H1 and Cr3+H2 are suggested. In centre Cr3+L, the Cr3+ ion replaces the Li+ ion and excess charge is compensated by two nearest Li+ vacancies on the same axis. In centres Cr3+H1 and Cr3+H2, the Li+ vacancies below and above the Cr3+ ion are, respectively, dissociated from the low temperature centre Cr3+L. The suggestions are supported by the theoretical calculations of EPR parameters D, g(parallel to) and g(perpendicular to) for the three Cr3+ centres. The reasonableness of these models is discussed.
Production of Secretory and Extracellular N-Linked Glycoproteins inEscherichia coli (2010)

The Campylobacter jejuni pgl gene cluster encodes a complete N-linked protein glycosylation pathway that can be functionally transferred into Escherichia coli. In this system, we analyzed the interplay between N-linked glycosylation, membrane translocation and folding of acceptor proteins in bacteria. We developed a recombinant N-glycan acceptor peptide tag that permits N-linked glycosylation of diverse recombinant proteins expressed in the periplasm of glycosylation-competent E. coli cells. With this "glycosylation tag," a clear difference was observed in the glycosylation patterns found on periplasmic proteins depending on their mode of inner membrane translocation (i.e., Sec, signal recognition particle [SRP], or twin-arginine translocation [Tat] export), indicating that the mode of protein export can influence N-glycosylation efficiency. We also established that engineered substrate proteins targeted to environments beyond the periplasm, such as the outer membrane, the membrane vesicles, and the extracellular medium, could serve as substrates for N-linked glycosylation. Taken together, our results demonstrate that the C. jejuni N-glycosylation machinery is compatible with distinct secretory mechanisms in E. coli, effectively expanding the N-linked glycome of recombinant E. coli. Moreover, this simple glycosylation tag strategy expands the glycoengineering toolbox and opens the door to bacterial synthesis of a wide array of recombinant glycoprotein conjugates.
Loblolly pine abietadienol/abietadienal oxidase PtAO (CYP720B1) is a multifunctional, multisubstrate cytochrome P450 monooxygenase (2005)

Cytochrome P450 monooxygenases (P450s) are important enzymes for generating some of the enormous structural diversity of plant terpenoid secondary metabolites. In conifers, P450s are involved in the formation of a suite of diterpene resin acids (DRAs). Despite their important role in constitutive and induced oleoresin defense, a P450 gene of DRA formation has not yet been identified. By using phylogenetic cluster analysis of P450-like ESTs from loblolly pine (Pinus taeda), functional cDNA screening in yeast (Saccharomyces cerevisiae), and in vitro enzyme characterization, we cloned and identified a multifunctional and multisubstrate cytochrome P450 enzyme, CYP720B1 [abietadienol/abietadienal oxidase (PtAO)]. PtAO catalyzes an array of consecutive oxidation steps with several different diterpenol and diterpenal intermediates in loblolly pine DRA biosynthesis. Recombinant PtAO oxidized the respective carbon 18 of abietadienol, abietadienal, levopimaradienol, isopimara-7,15-dienol, isopimara-7,15-dienal, dehydroabietadienol, and dehydroabietadienal with apparent Michaelis-Menten (K(m)) values of 0.5-5.3 muM. PtAO expressed in yeast also catalyzed in vivo oxidation of abietadiene to abietic acid, but with activity much lower than with abietadienol or abietadienal. Consistent with a role of DRAs in conifer defense, PtAO transcript levels increased upon simulated insect attack using methyl jasmonate treatment of loblolly pine. The multisubstrate, multifunctional P450 diterpene oxidase PtAO, in concert with expression of a family of single-product and multiproduct diterpene synthases, allows for formation of a diverse suite of DRA defense metabolites in long-lived conifers.
Transport in high mobility amorphous wide band gap indium zinc oxide films (2005)

Abstract This paper discusses the electron transport in the n‐type amorphous indium–zinc–oxygen system produced at room temperature by rf magnetron sputtering, under different oxygen partial pressures. The data show that the transport is not band tail limited, as it happens in conventional disordered semiconductors, but highly dependent on its ionicity, which explains the very high mobilities (≥60 cm 2 V –1 s –1 ) achieved. The room temperature dependence of the Hall mobility on the carrier concentration presents a reverse behaviour than the one observed in conventional crystalline/polycrystalline semi‐conductors, explained mainly by the presence of charged structural defects in excess of 4 × 10 10 cm –2 that scatter the electrons that pass through them. (© 2005 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Camel single-domain antibody inhibits enzyme by mimicking carbohydrate substrate (1998)

Whereas antibodies have demonstrated the ability to mimic various compounds, classic heavy/light-chain antibodies may be limited in their applications. First, they tend not to bind enzyme active site clefts. Second, their size and complexity present problems in identifying key elements for binding and in using these elements to produce clinically valuable compounds. We have previously shown how cAb-Lys3, a single variable domain fragment derived from a lysozyme-specific camel antibody naturally lacking light chains, overcomes the first limitation to become the first antibody structure observed penetrating an enzyme active site. We now demonstrate how cAb-Lys3 mimics the oligosaccharide substrate functionally (inhibition constant for lysozyme, 50 nM) and structurally (lysozyme buried surface areas, hydrogen bond partners, and hydrophobic contacts are similar to those seen in sugar-complexed structures). Most striking is the mimicry by the antibody complementary determining region 3 (CDR3) loop, especially Ala104, which mimics the subsite C sugar 2-acetamido group; this group has previously been identified as a key feature in binding lysozyme. Comparative simplicity, high affinity and specificity, potential to reach and interact with active sites, and ability to mimic substrate suggest that camel heavy-chain antibodies present advantages over classic antibodies in the design, production, and application of clinically valuable compounds.
Interaction of Heparin-Binding EGF-Like Growth Factor (HB-EGF) with the Epidermal Growth Factor Receptor: Modulation by Heparin, Heparinase, or Synthetic Heparin-Binding HB-EGF Fragments (1992)

The binding of heparin-binding EGF-like growth factor (HB-EGF) to the epidermal growth factor (EGF) receptor of human endometrial carcinoma cells was compared to that of EGF using an 125I-EGF radioreceptor assay. The inhibitory effect of HB-EGF on 125I-EGF binding was reversed either in the presence of heparin (but not by chondroitin sulfate) or by pre-treating the cells with heparinase. These treatments did not affect the binding of EGF to its receptor. To map potential regions in the HB-EGF molecule that mediate its heparin-dependent interaction with the EGF receptor, HB-EGF peptides were synthesized that were non-homologous to EGF. Accordingly residues 20-25 and 36-41, but not residues 8-19, of HB-EGF were found to be (i) heparin-binding and (ii) modulators of HB-EGF (but not of EGF) binding to the EGF receptor.
Beyond a House of Sticks (2019)

Current efforts establishing semantic metadata standards for the built environment span academia [3], industry [1] and standards bodies [2, 28]. For these standards to be effective, they must be clearly defined and easily extensible, encourage consistency in their usage, and integrate cleanly with existing industrial standards, such as BACnet. There is a natural tension between informal tag-based systems that rely upon idiom and convention for meaning, and formal ontologies amenable to automated tooling.
On-the-fly web content integrity check boosts users' confidence (2002)

Malicious attacks on Web servers by intruders and hackers are prime concerns of organizations, administrators of Web sites, as well as users who access them.
Sensitive solid-phase radioimmunoassay for detection of human immunoglobulin G antibodies to varicella-zoster virus (1979)

A sensitive solid-phase radioimmunoassay for detection of antibodies to varicella-zoster virus (VZV) is described. The antigen consisted of a sonically disrupted extract of VZV-infected human embryo cells. 125I-labeled rabbit anti-human immunoglobulin G (IgG) specific for the Fc portion of human IgG was used to detect human IgG bound to viral antigen. With this technique, 193 human sera were evaluated for their IgG antibody titer against ZVZ. Subjects included 62 healthy adults, 33 young children (12 healthy), and 49 patients. Titers obtained by the radioimmunoassay were compared with those obtained by indirect fluoresence antibody staining of membrane antigen. The radioimmunoassay technique described gave titers approximately 5 X 10(4) times higher than those shown by indirect fluorescence. It can be used for routine diagnosis, but is especially suited to determining immune status to VZV, as defined by presence or absence of antibodies to the virus; for epidemiological studies; or for determining patients at risk who are exposed to the virus. No heterotypic titer rises to VZV were observed in sera with fourfold or greater rises to Epstein-Barr virus or cytomegalovirus. Sera of eight subjects with fourfold or greater titer rises to herpes simplex virus reacted in various ways: in six cases no significant change occurred in titer to VZV; one had a significant decrease in titer by the radioimmunoassay; and one had a significant increase. Possible reasons for these titer changes are discussed.
A DNA-recombinogenic activity in human cells (1984)

A DNA recombining protein has been partly purified from cell lines derived from patients suffering from the hereditary disease, Bloom's syndrome. The protein induces the formation of displacement loops in phi X174 RFI DNA molecules after the addition of single-stranded DNA fragments. A filter binding method and electron microscopy were used to determine the reaction. The recombinogenic protein is dependent on divalent cations and ATP for activity.
CRISPR–Cas system enables fast and simple genome editing of industrial Saccharomyces cerevisiae strains (2015)

There is a demand to develop 3rd generation biorefineries that integrate energy production with the production of higher value chemicals from renewable feedstocks. Here, robust and stress-tolerant industrial strains of <i>Saccharomyces cerevisiae</i> will be suitable production organisms. However, their genetic manipulation is challenging, as they are usually diploid or polyploid. Therefore, there is a need to develop more efficient genetic engineering tools. We applied a CRISPR-Cas9 system for genome editing of different industrial strains, and show simultaneous disruption of two alleles of a gene in several unrelated strains with the efficiency ranging between 65% and 78%. We also achieved simultaneous disruption and knock-in of a reporter gene, and demonstrate the applicability of the method by designing lactic acid-producing strains in a single transformation event, where insertion of a heterologous gene and disruption of two endogenous genes occurred simultaneously. Our study provides a foundation for efficient engineering of industrial yeast cell factories.
Interframe Redundancy Reduction of Video Signals Generated by Translating Objects (1977)

In interframe coding the content of the frame memory can also be utilized for the prediction of the luminances of moving area picture elements (pels), provided that their displacement has been measured and transmitted. After an analysis of methods for the optimal segmentation of the image into areas corresponding to background, translating objects, and areas not predictable from the previous frame, experimental results of the coding are given; it can be seen that the bit rates are about halved with respect to plain interframe coding.
Retinobenzoic acids. 2. Structure-activity relationships of chalcone-4-carboxylic acids and flavone-4'-carboxylic acids (1989)

The structure-activity relationships of (E)-chalcone-4-carboxylic acids, which are retinoidal benzoic acids represented by R-Ph-X-Ph-COOH (4, X = -COCH = CH-), are discussed on the basis of differentiation-inducing activity on human promyelocytic leukemia cells HL-60. The activity was increased by the substitution of a bulky alkyl group(s) (R), and among such compounds, (E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid (Ch55) and (E)-4-[3-oxo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1 -propenyl]benzoic acid (Ch80) are several times more active than retinoic acid. Though the stable conformer of chalcone derivatives is linear (s-cis form), the conformationally restricted analogue 4-(6,7,8,9-tetrahydro-6,6,9,9-tetramethyl-4H-4-oxonaphtho[2,3-b]py ran-2-yl)benzoic acid (Fv80) is more active than Ch80. While the effect of introduction of an oxygen atom varied, 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2 - naphthalenyl)-1-propenyl]benzoic acid (Re80), regarded as a derivative of Ch80 with two additional hydroxyl groups, has very strong activity.
Thin-film thickness measurements with thermal waves (1983)

We have developed a method for measuring the thickness of thin films that is nondestructive, noncontact and that can make measurements with 2-μm spatial resolution (i.e., 2-μm spot size) on both optically opaque as well as optically transparent films. With this method, which is based on the use of high-frequency thermal waves, thicknesses of Al and SiO2 films on Si substrates have been measured in the 500–25 000-Å range.
Intelligent Scheduling of Hybrid and Electric Vehicle Storage Capacity in a Parking Lot for Profit Maximization in Grid Power Transactions (2008)

This paper proposes an intelligent method for scheduling usage of available energy storage capacity from plugin hybrid electric vehicles (PHEV) and electric vehicles (EV). The batteries on these vehicles can either provide power to the grid when parked, known as vehicle-to-grid (V2G) concept or take power from the grid to charge the batteries on the vehicles. A scalable parking lot model is developed with different parameters assigned to fleets of vehicles. The size of the parking lot is assumed to be large enough to accommodate the number of vehicles performing grid transactions. In order to figure out the appropriate charge and discharge times throughout the day, binary particle swarm optimization is applied. Price curves from the California ISO database are used in this study to have realistic price fluctuations. Finding optimal solutions that maximize profits to vehicle owners while satisfying system and vehicle owners' constraints is the objective of this study. Different fleets of vehicles are used to approximate varying customer base and demonstrate the scalability of parking lots for V2G. The results are compared for consistency and scalability. Discussions on how thistechnique can be applied to other grid issues such as peaking power are included at the end.
Dietary supplementation of neutral and acidic oligosaccharides enhances Th1‐dependent vaccination responses in mice (2007)

Immunomodulatory effects of oligosaccharide preparations that resemble chemical and functional aspects of human milk oligosaccharides (HMOS) were studied for the development of new concepts in infant nutrition. A dose range of 1-5% (w/w) dietary pectin-derived acidic oligosaccharides (AOS) was tested in a murine influenza vaccination model. In addition, combinations of AOS and a 9:1 mixture of galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) were tested at a fixed total dietary dose of 2% (w/w). It was found that AOS significantly enhanced vaccine-specific delayed-type hypersensitivity (DTH) responses in a dose-dependent manner. This was accompanied by a reduction in T-helper2 (Th2) cytokine production by splenocytes in vitro. Overall, this indicates that the systemic immune response to the vaccine was Th1-skewed by the dietary intervention. Combinations of GOS/FOS and AOS were more effective in enhancing DTH responses than either of the oligosaccharides alone, suggesting interaction effects between these agents. Similar to effects in infants, supplementation of the murine diets with GOS/FOS and combinations of GOS/FOS and AOS for 6-wk enhanced the proportion of fecal bifidobacteria and lactobacilli, but AOS alone did not. In conclusion, these data indicate that GOS/FOS and AOS enhance systemic Th1-dependent immune responses in a murine vaccination model. As Th1-responses are weak in early life in humans, this might suggest that application of these oligosaccharides in infant formulas will be beneficial for the development of the infant's immune system.