gebhart/patrepeval huggingface dataset:
Selective inhibition of cholesterol synthesis by cell-free preparations of rat liver by using inhibitors of cytoplasmic acetoacetyl-coenzyme A thiolase. (1975)

Cytoplasmic acetoacetyl-CoA thiolase (acetyl-CoA C-acetyltransferase, EC 2.3.1.9) was partially purified from rat liver. The enzyme was irreversibly inactivated by 4-bromocrotonyl-CoA, but-3-ynoyl-CoA, pent-3-ynoyl-CoA and dec-3-ynoyl-CoA. In the case of the alk-3-ynoyl-CoA esters the potency as alkylating agents of acetoacetyl-CoA thiolase decreased with increased chain length of the alk-3-ynoyl moiety. Advantage was taken of the specific action of alk-3-ynoyl-CoA esters on acetoacetyl-CoA thiolase to show that in a postmitochondrial fraction from rat liver they are effective inhibitors of cholesterol synthesis from sodium [2-14C]acetate under conditions when mevalonate conversion into cholesterol and fatty acid synthesis are unafffected. Short-chain alk-3-ynoic acids have little effect on sterol synthesis, although dec-3-ynoic acid is an effective inhibitor owing to its conversion into the CoA ester by the microsomal fatty acyl-CoA synthetase.
Multiple-Challenge Study of Host Susceptibility to Norwalk Gastroenteritis in US Adults (1990)

In a multiple-challenge study of US adult volunteers with low or high levels of serum antibody to Norwalk virus, Norwalk inoculum 8FIIa was administered to 42 subjects, 22 were challenged 6 months later, and 19 received a third challenge after 6 more months. All 12 with high (greater than or equal to 1:200) but only 19 of 30 with low (less than 1:100) prechallenge titers experienced illness or a fourfold increase in titer after the first challenge (P less than .025). Only 4 of those challenged twice became ill; all had low initial titers but 3 had high titers before the second challenge. None became ill after a third challenge. Nine (47%) had high titers immediately before the third challenge; 3 had low titers before and after each challenge and remained asymptomatic. Thus, preexisting serum antibody to Norwalk virus does not seem to be associated with protective immunity, but antibody levels become associated with protection after repetitive exposure. Short-term resistance lasts greater than or equal to 6 months after challenge, and a small percentage of resistant individuals maintain low antibody titers even after multiple challenges.
Transport function of transcobalamin II (1972)

The uptake of free and bound (57)CoB(12), principally to transcobalamin II (TC II), was studied in isolated, perfused liver and kidney of the dog. (1) There was good uptake of canine TC II-B(12) by both organs. (2) In the liver TC II enhanced uptake over that of free B-12. (3) Renal uptake of free B-12 was greater than that of TC II-B(12). Free B-12 was neither lost in the urine nor returned to the circulation. (4) On a per gram tissue basis, renal uptake of TC II-B(12) was greater than hepatic. (5) There was renal release or production of TC II (6) Some TC II but more of a larger molecular size binder came from the liver. (7) Passing free B-12 through the kidney enhanced its uptake by the liver. (8) Passing free B-12 through the liver depressed its uptake by the kidney. (9) It is postulated that the distribution of B-12 can be modified by (a) different responses of tissue to TC II-B(12), (b) synthesis of TC II by an organ, and (c) the effects of B-12 passing through one organ to another.
Aspergillus niger genome-wide analysis reveals a large number of novel alpha-glucan acting enzymes with unexpected expression profiles (2008)

The filamentous ascomycete Aspergillus niger is well known for its ability to produce a large variety of enzymes for the degradation of plant polysaccharide material. A major carbon and energy source for this soil fungus is starch, which can be degraded by the concerted action of alpha-amylase, glucoamylase and alpha-glucosidase enzymes, members of the glycoside hydrolase (GH) families 13, 15 and 31, respectively. In this study we have combined analysis of the genome sequence of A. niger CBS 513.88 with microarray experiments to identify novel enzymes from these families and to predict their physiological functions. We have identified 17 previously unknown family GH13, 15 and 31 enzymes in the A. niger genome, all of which have orthologues in other aspergilli. Only two of the newly identified enzymes, a putative alpha-glucosidase (AgdB) and an alpha-amylase (AmyC), were predicted to play a role in starch degradation. The expression of the majority of the genes identified was not induced by maltose as carbon source, and not dependent on the presence of AmyR, the transcriptional regulator for starch degrading enzymes. The possible physiological functions of the other predicted family GH13, GH15 and GH31 enzymes, including intracellular enzymes and cell wall associated proteins, in alternative alpha-glucan modifying processes are discussed.
The Proportion of Specific Viral Subpopulations in Attenuated Arkansas Delmarva Poultry Industry Infectious Bronchitis Vaccines Influences Vaccination Outcome (2012)

We investigated the significance of differing proportions of specific subpopulations among commercial Arkansas (Ark) Delmarva poultry industry (DPI) vaccines with regard to vaccination outcome. Two ArkDPI-derived vaccines that contain a higher proportion of viruses with S1 genes that become selected during replication in chickens exhibited more rapid establishment of those selected subpopulations in chickens, produced significantly higher viral loads in tears, and induced higher antibody responses compared with two other ArkDPI vaccines with lower proportions of viruses that become selected in chickens. The presence of higher proportions of selected subpopulations was also associated with a significantly higher incidence of respiratory signs early after vaccination and in some cases more severe tracheal lesions. However, one of the ArkDPI-derived vaccines with a lower proportion of selected subpopulations, despite producing a lower viral load in tears, also induced a higher incidence of respiratory signs later after vaccination and more severe tracheal lesions. Furthermore, one of the ArkDPI-derived vaccines with a higher proportion of selected subpopulations, despite producing a higher viral loads in tears, resulted in less severe tracheal damage. These discrepancies suggest that infectious bronchitis virus (IBV) load in tears may not always predict degree of tracheal damage and that phenotypic characteristics other than S1 may also be involved in severity of vaccine reactions following ArkDPI vaccine administration. We observed lower antibody responses to the vaccines that produced lower viral loads, which might contribute to the persistence of Ark serotype IBV vaccines observed in commercial flocks.
The Effect of Whole Ejaculate Filtration on the Morphology and the Fertility of Bovine Semen (1990)

A Sephadex G-15 filtration method was developed to remove abnormal and nonmotile bull sperm from an entire ejaculate. The efficiency of filtration was determined by adding freeze-killed sperm to the ejaculate or using ejaculates with elevated numbers of abnormal cells induced by scrotal insulation. A fertility trial, using split ejaculates, compared fertility of filtered and unfiltered semen. After filtration, samples with 0, 25, and 50% killed cells added contained 77 to 81% motile cells. Addition of 75% killed sperm resulted in significant decrease (52%) of motile cells following filtration. Morphologic examination of semen with elevated numbers of abnormal cells revealed higher percentages of sperm with normal shaped heads and normal or swollen acrosomes after filtration than in unfiltered samples. Percentage of pear-shaped heads, lifted acrosomes, and bent tails decreased after filtration. Six high fertility and six low fertility bulls were used to evaluate fertility of filtered semen. Filtering increased motile sperm from 51 to 57% and from 36 to 50% for the high and low fertility bulls, respectively. The 60- to 90-d nonreturn rates for high fertility bulls were not increased by filtering (73 vs. 72%). However, filtering significantly improved the nonreturn rates for the low fertility bulls (61 vs. 67%).
The ERK/MAPK pathway, as a target for the treatment of neuropathic pain (2005)

Peripheral nerve injury produces neuropathic pain as well as phosphorylation of mitogen activated protein kinase (MAPK) family in dorsal root ganglia (DRG) and dorsal horn. Following nerve injury, phosphorylation of extracellular signal-regulated protein kinase (ERK), an important member of this family, is sequentially increased in neurons, microglia and astrocytes of the dorsal horn and gracile nucleus, and in injured large DRG neurons. Nerve injury-induced phosphorylation of ERK occurs early and is long-lasting. In several animal models of neuropathic pain, MEK inhibitors, known to suppress the synthesis of ERK, have proven effective to alleviate pain at various time points. Thus, the regulation of ERK/MAPK can be considered as a promising therapeutic target for the treatment of neuropathic pain.
Lattice-Oriented Growth of Single-Walled Carbon Nanotubes (2000)

Single-walled carbon nanotubes (SWNTs) with preferred 2D orientations were synthesized for the first time by chemical vapor deposition (CVD) of methane on silicon surfaces terminated with hydrogen, native oxide, and an ultrathin aluminum layer. The SWNTs grown on Si(100)-based surfaces take two perpendicular directions, and those grown on Si(111)-based surfaces take three preferred directions that are separated by 60°. Simulations of SWNTs on Si(100) and Si(111) surfaces indicate that the observed orientation locking is the result of interactions between nanotubes and the surface lattices. The calculated orientations of energy minimums accord exactly with the experimental results and are independent of the tube chirality as observed. In addition, the calculations also show that the (111) surface is stickier than (100), thus explaining the observation that SWNTs grown on Si(111) surfaces are shorter than those on Si(100) surfaces.
Time-action Profile of Inhaled Insulin (1997)

We compared the pharmacodynamics of insulin after inhalation of 99 U microcrystalline solid insulin and subcutaneous injection of 10 U regular insulin and intravenous injection of 5 U regular insulin. The time-action profiles of the three insulin administrations were studied in 11 healthy volunteers using the euglycaemic glucose clamp technique. The insulins were administered to each volunteer on three separate occasions in random order. Onset of action, assessed as glucose infusion rate, after insulin inhalation was substantially more rapid than after subcutaneous injection and half-maximal action was reached earlier (31 +/- 17 vs 54 +/- 12 min; p < 0.001). Maximal metabolic response was reached earlier after insulin inhalation in comparison to subcutaneous injection (108 +/- 49 vs 147 +/- 53 min; p < 0.001). The maximal glucose infusion rate after inhalation of insulin was lower than after subcutaneous insulin injection (6.2 +/2- 2.4 vs 9.1 +/- 2.5 mg kg-1 min-1; p < 0.001). The glucose infusion rates in the first 60 min after inhalation were significantly greater than after insulin injection (area under the glucose infusion rate curve: 0.23 +/- 0.12 vs 0.13 +/- 0.08 g kg-1 60 min-1; p < 0.001). However, the total metabolic effect after inhalation was significantly lower than after insulin injection (1.44 +/- 0.68 vs 1.90 +/- 0.47 g kg-1 360 min-1; p < 0.001). Relative effectiveness of inhaled insulin calculated with regard to the data from the intravenous insulin application was 9.5 +/- 4.1% and of the subcutaneous insulin application was 7.6 +/- 2.9%. With its rapid onset of action, inhaled insulin might have potential for clinical use.
Micro-Raman spectroscopic identification of bacterial cells of the genus Staphylococcus and dependence on their cultivation conditions (2005)

Microbial contamination is not only a medical problem, but also plays a large role in pharmaceutical clean room production and food processing technology. Therefore many techniques were developed to achieve differentiation and identification of microorganisms. Among these methods vibrational spectroscopic techniques (IR, Raman and SERS) are useful tools because of their rapidity and sensitivity. Recently we have shown that micro-Raman spectroscopy in combination with a support vector machine is an extremely capable approach for a fast and reliable, non-destructive online identification of single bacteria belonging to different genera. In order to simulate different environmental conditions we analyzed in this contribution different Staphylococcus strains with varying cultivation conditions in order to evaluate our method with a reliable dataset. First, micro-Raman spectra of the bulk material and single bacterial cells that were grown under the same conditions were recorded and used separately for a distinct chemotaxonomic classification of the strains. Furthermore Raman spectra were recorded from single bacterial cells that were cultured under various conditions to study the influence of cultivation on the discrimination ability. This dataset was analyzed both with a hierarchical cluster analysis (HCA) and a support vector machine (SVM).
A Highly Conserved Signal Controls Degradation of 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) Reductase in Eukaryotes (1999)

Sterol synthesis by the mevalonate pathway is modulated, in part, through feedback-regulated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). In both mammals and yeast, a non-sterol isoprenoid signal positively regulates the rate of HMGR degradation. To define more precisely the molecule that serves as the source of this signal, we have conducted both pharmacological and genetic manipulations of the mevalonate pathway in yeast. We now demonstrate that farnesyl diphosphate (FPP) is the source of the positive signal for Hmg2p degradation in yeast. This FPP-derived signal does not act by altering the endoplasmic reticulum degradation machinery in general. Rather, the FPP-derived signal specifically modulates Hmg2p stability. In mammalian cells, an FPP-derived molecule also serves as a positive signal for HMGR degradation. Thus, both yeast and mammalian cells employ the same strategy for regulation of HMGR degradation, perhaps by conserved molecular processes.
A knowledge‐based approach for screening chemical structures within de novo molecular evolution (2010)

Abstract Despite the advantage of employing evolutionary algorithms (EAs) for de novo creation of novel molecular structures with optimal properties, the approach is hampered by sampling chemically undesirable structures. Such structures are undesirable for different reasons, such as a critical structural pattern may be ignored or too many rotational degrees of freedom exist for conformational search. A new method is presented which creates a user‐defined structure filter, here referred to as the bias filter (BF)b, generated from a set of molecules representing typical structure types that are allowed to evolve in the de novo process. The BF can be seen as constraining the chemical structure space according to external requirements given by the user. No explicit programming of structure rules is necessary which makes the proposed method much more intuitive and user friendly than other methods commonly used in de novo applications. We have tested the proposed method in the process of evolving a set of Factor Xa inhibitors where the aim is to create molecules with optimal log P values. The de novo GeneGear system developed in our group is responsible for the corresponding evolutionary computation and bias filtering. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling (2017)

4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 4-1BB also can bind to the tandem repeat-type lectin galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in galectin-9 (Gal-9)-deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2-Å resolution. We found that similar to other TNFRSFs, m4-1BB has four cysteine-rich domains (CRDs). However, the organization of CRD1 and the orientation of CRD3 and CRD4 with respect to CRD2 in the m4-1BB structure distinctly differed from those of other TNFRSFs. Moreover, we mapped two Asn residues within CRD4 that are <i>N</i>-linked glycosylated and mediate m4-1BB binding to Gal-9. Kinetics studies of m4-1BB disclosed a very tight nanomolar binding affinity to m4-1BBL with an unexpectedly strong avidity effect. Both N- and C-terminal domains of Gal-9 bound m4-1BB, but with lower affinity compared with m4-1BBL. Although the TNF homology domain (THD) of human (h)4-1BBL forms non-covalent trimers, we found that m4-1BBL formed a covalent dimer via 2 cysteines absent in h4-1BBL. As multimerization and clustering is a prerequisite for TNFR intracellular signaling, and as m4-1BBL can only recruit two m4-1BB monomers, we hypothesize that m4-1BBL and Gal-9 act together to aid aggregation of m4-1BB monomers to efficiently initiate m4-1BB signaling.
Human cord blood cells induce angiogenesis following myocardial infarction in NOD/-mice (2005)

hUCB cells migrate to infarcted, not to normal myocardium, where they engraft, participate in neoangiogenesis, and beneficially influence remodelling processes. Cord blood cells may hence be useful for cell therapy of ischemic heart disease.
An efficient total synthesis of agrobactin and its gallium(III) chelate (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn efficient total synthesis of agrobactin and its gallium(III) chelateR. J. Bergeron, J. S. McManis, J. Dionis, and J. R. GarlichCite this: J. Org. Chem. 1985, 50, 15, 2780–2782Publication Date (Print):July 1, 1985Publication History Published online1 May 2002Published inissue 1 July 1985https://pubs.acs.org/doi/10.1021/jo00215a037https://doi.org/10.1021/jo00215a037research-articleACS PublicationsRequest reuse permissionsArticle Views380Altmetric-Citations34LEARN 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
Regulation of the phospholipase C‐γ2 pathway in B cells (2000)

In B lymphocytes, a signaling complex that contributes to cell fate decisions is the B-cell antigen receptor (BCR), with different extents of receptor engagement leading to such outcomes as cell death, survival, or proliferation. Here, based upon the available genetic and biochemical data of the BCR signal components, we discuss several mechanisms by which BCR signals are propagated and modified, with specific emphasis on the phospholipase C (PLC)-gamma2-calcium pathway Gene-targeting experiments in DT40 chicken B cells highlighted the importance of the intracellular protein tyrosine kinases Syk and Btk in PLC-gamma2 activation. Until recently, the molecular mechanism underlying the double requirement for Syk and Btk in PLC-gamma2 activation remained unclear, but new data suggest that an adapter molecule, B-cell linker protein (alternatively named SLP-65 or BASH), phosphorylated by Syk, provides docking sites for Btk SH2 domain as well as PLC-gamma2 SH2 domains, thus bringing Btk into close proximity with PLC-gamma2. The activated Btk then phosphorylates PLC-gamma2, leading to its activation. The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). Binding of IP3 to the IP3 receptors is essential for triggering a calcium release from the ER and subsequent entry of extracellular calcium. Balancing these activation signals in the PLC-gamma2-calcium pathway are the inhibitory receptors expressed on B cells, FcyRII and paired immunoglobin-like receptor (PIR)-B. Although both FcyRII and PIR-B inhibits the BCR-mediated [Ca2+]i increase, the inhibitory mechanisms of these receptors are distinct. The FcyRII-mediated inhibitory signal is dependent on lipid phosphatase SHIP, whereas the PIR-B requires redundant functions of protein phosphatases SHP-1 and SHP-2. Thus, PIR-B and FcgammaRII inhibit calcium signals by utilizing two distinct signaling molecules, thereby contributing to setting threshold levels for activation signals as well as terminating activation responses.
Selective reductions. 26. Lithium triethylborohydride as an exceptionally powerful and selective reducing agent in organic synthesis. Exploration of the reactions with selected organic compounds containing representative functional groups (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective reductions. 26. Lithium triethylborohydride as an exceptionally powerful and selective reducing agent in organic synthesis. Exploration of the reactions with selected organic compounds containing representative functional groupsHerbert C. Brown, S. C. Kim, and S. KrishnamurthyCite this: J. Org. Chem. 1980, 45, 1, 1–12Publication Date (Print):January 1, 1980Publication History Published online1 May 2002Published inissue 1 January 1980https://pubs.acs.org/doi/10.1021/jo01289a001https://doi.org/10.1021/jo01289a001research-articleACS PublicationsRequest reuse permissionsArticle Views4689Altmetric-Citations186LEARN 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
Fabrication of Nanopores in a 100-nm Thick Si<SUB>3</SUB>N<SUB>4</SUB> Membrane (2006)

Textured alumina films have been used to fabricate nanoscale pores in Si3N4 membranes. A few nanometer-thick alumina layer was used as a masking material for nanopore fabrication, and the pattern was transferred into a 100-nm thick, 200 microm x 200 microm Si3N4 membrane by reactive ion etching (RIE). The nanopores were found to be concentrated in a approximately 150-microm diameter region at the center of the membrane.