gebhart/patrepeval huggingface dataset:
CTL model checking based on forward state traversal (1996)

We present a CTL model checking algorithm based mainly on forward state traversal, which can check many realistic CTL properties without doing backward state traversal. This algorithm is effective in many situations where backward state traversal is more expensive than forward state traversal. We combine it with BDD-based state traversal techniques using partitioned transition relations. Experimental results show that our method can verify actual CTL properties of large industrial models which cannot be handled by conventional model checkers.
Prostate‐derived factor as a paracrine and autocrine factor for the proliferation of androgen receptor‐positive human prostate cancer cells (2007)

PDF promotes AR-positive prostate tumor progression through upregulating cell proliferation via ERK1/2 signal pathway.
Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTApplications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial LibrariesMark A. Gallop, Ronald W. Barrett, William J. Dower, Stephen P. A. Fodor, and Eric M. GordonCite this: J. Med. Chem. 1994, 37, 9, 1233–1251Publication Date (Print):April 1, 1994Publication History Published online1 May 2002Published inissue 1 April 1994https://pubs.acs.org/doi/10.1021/jm00035a001https://doi.org/10.1021/jm00035a001research-articleACS PublicationsRequest reuse permissionsArticle Views2715Altmetric-Citations976LEARN 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
2-5A accumulates to high levels in interferon-treated, vaccinia virus-infected cells in the absence of any inhibition of virus replication (1984)

We investigated the effects of interferon treatment on virus yield, protein synthesis, and the 2-5A system in vaccinia virus-infected HeLa, L929, and CV1 cells. Under the culture conditions used, vaccinia virus replication was relatively insensitive to the antiviral effects of interferon. In L929 and HeLa cells, interferon at 400 reference units (r.u.) per ml had little effect on viral protein synthesis, the virus-induced inhibition of host protein synthesis, or virus yield: 2,000 to 20,000 r.u./ml were required to inhibit these. Despite this, high levels (up to 5 microM) of 2-5A [ppp(A2'p)nA; n greater than or equal to 2] were found during vaccinia infection of all of these types of cells treated with 400 r.u. of interferon per ml, i.e., at interferon concentrations too low to inhibit significantly virus growth. High levels (up to 5 microM) were also found in non-interferon-treated HeLa cells (which have a high constitutive level of 2-5A synthetase) in which vaccinia virus replicates perfectly well. It can be concluded that high levels of 2-5A per se have no necessary antiviral effect on vaccinia virus in these systems. These results are in marked contrast to those obtained here and previously with encephalomyocarditis virus. For example, in HeLa cells less than 20 nM 2-5A accumulated, but virus replication was inhibited by 50 r.u. of interferon per ml (Silverman et al., Eur. J. Biochem. 124:131-138, 1982). The characteristic cleavage of rRNA by the 2-5A-dependent RNase was delayed relative to 2-5A accumulation in the vaccinia virus-infected cells. This delay was not the result of either defective 2-5A or of a stable virus-induced inhibition of the 2-5A-dependent RNase; 2-5A extracted from the cells had full biological activity when assayed by activation of the 2-5A-dependent RNase in cell extract, and the 2-5A-dependent RNase extracted from the vaccinia virus-infected cells was fully active in vitro. The basis for the delay remains to be determined. High levels of 2-5A were not observed when late (DNA synthesis-dependent) vaccinia transcription was inhibited by either cycloheximide or cytosine arabinoside. The only known activator of the 2-5A synthetase is double-stranded RNA. The presence of 2-5A therefore implies the natural occurrence of double-stranded structures in late viral RNA in intact vaccinia virus-infected cells.
Fluorescence‐based methods for evaluating the RNA affinity and specificity of HIV‐1 Rev–RRE inhibitors (2003)

RNA plays a pivotal role in the replication of all organisms, including viral and bacterial pathogens. The development of small molecules that selectively interfere with undesired RNA activity is a promising new direction for drug design. Currently, there are no anti-HIV treatments that target nucleic acids. This article presents the HIV-1 Rev response element (RRE) as an important focus for the development of antiviral agents that target RNA. The Rev binding site on the RRE is highly conserved, even between different groups of HIV-1 isolates. Compounds that inhibit HIV replication by binding to the RRE and displacing Rev are therefore expected to retain activity across groups of genetically diverse HIV infections. Systematic evaluations of both the RRE affinity and specificity of numerous small molecule inhibitors are essential for deciphering the parameters that govern effective RRE recognition. This article discusses fluorescence-based techniques that are useful for probing a small molecule's RRE affinity and its ability to inhibit Rev-RRE binding. Rev displacement experiments can be conducted by observing the fluorescence anisotropy of a fluorescein-labeled Rev peptide, or by quantifying its displacement from a solid-phase immobilized RRE. Experiments conducted in the presence of competing nucleic acids are useful for evaluating the RRE specificity of Rev-RRE inhibitors. The discovery and characterization of new RRE ligands are described. Eilatin is a polycyclic aromatic heterocycle that has at least one binding site on the RRE (apparent Kd is approximately 0.13 microM), but it does not displace Rev upon binding the RRE (IC50 > 3 microM). In contrast, ethidium bromide and two eilatin-containing metal complexes show better consistency between their RRE affinity and their ability to displace a fluorescent Rev peptide from the RRE. These results highlight the importance of conducting orthogonal binding assays that establish both the RNA affinity of a small molecule and its ability to inhibit the function of the RNA target. Some Rev-RRE inhibitors, including ethidium bromide, Lambda-[Ru(bpy)(2)eilatin]2+, and Delta-[Ru(bpy)(2)eilatin]2+ also inhibit HIV-1 gene expression in cell cultures (IC50 = 0.2-3 microM). These (and similar) results should facilitate the future discovery and implementation of anti-HIV drugs that are targeted to viral RNA sites. In addition, a deeper general understanding of RNA-small molecule recognition will assist in the effective targeting of other therapeutically important RNA sites.
Unified, Efficient, and Scalable Synthesis of Halichondrins: Zirconium/Nickel‐Mediated One‐Pot Ketone Synthesis as the Final Coupling Reaction (2017)

Unified, efficient, and scalable syntheses of the halichondrin natural products are reported. A newly developed Zr/Ni-mediated one-pot ketone synthesis was used to couple the two halves of the final product at a late stage in the synthesis. With the use of a slight excess of the left halves, the desired ketones were isolated in yields of 80-90 %. The halichondrins were obtained from these ketones in two steps, namely desilylation and [5,5]-spiroketal formation. The new synthetic route was effective for the total synthesis of all members in the homohalichondrin subgroup. The scalability of this process was demonstrated with halichondrin B; 150 mg of halichondrin B (68 % overall yield) were obtained from 200 mg of the right-half precursor.
DNA-Tethered Hoechst Groove-Binding Agents:  Duplex Stabilization and Fluorescence Characteristics (1996)

Fluorescent Hoechst 33258 analogues have been synthesized in which the terminal phenol moiety is employed as a site for the introduction of a linker to permit covalent attachment of the fluorophores to oligo(deoxynucleotides). Hybridization by the DNA−Hoechst conjugates to target sequences generates the DNA minor groove structure and triggers a binding event by the tethered Hoechst agent. The attendant fluorescence signal reports upon this hybridization event. Conjugation of the Hoechst derivatives to the DNA sequences employs a cystamine linker tethered to an internucleotide phosphorus residue. This mode of conjugation maximizes the versatility of linker placement and minimizes the associated chemistry required to introduce the linker. Two related Hoechst derivatives have been synthesized; both contain a bromoacetamido linker for conjugation to the oligonucleotides. With each Hoechst derivative, two pairs of diastereomeric (Rp and Sp) oligo(deoxynucleotide) conjugates were prepared to provide the tethered Hoechst groove binders with two different orientations within the dA-dT rich minor groove. Tm measurements suggest that while all of the conjugates provide some increased duplex stability, the diastereomeric conjugates tentatively assigned the Rp configuration exhibit nearly 20 °C increases in Tm values for the double-stranded dodecameric complexes, while those tentatively assigned as the Sp diastereomers exhibit only moderate 4−8 °C increases in Tm values. The fluorescence characteristics of the conjugates are more variable, with one complex exhibiting a 23-fold enhancement in quantum yield effects, very similar to that observed for a free untethered Hoechst 33258 fluorophore bound to duplex DNA.
After Spontaneous Hypothermia during Hemorrhagic Shock, Continuing Mild Hypothermia (34??C) Improves Early but Not Late Survival in Rats (2003)

After spontaneous cooling during moderately severe HS, mild, controlled hypothermia during resuscitation does not seem to affect long-term survival. After more severe HS, hypothermia increases survival time. Hypothermia supports arterial pressure during resuscitation from severe HS.
Proteomic Identification of 14-3-3ζ as a Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Substrate: Role in Dimer Formation and Ligand Binding (2003)

Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MAPKAPK2) mediates multiple p38 MAPK-dependent inflammatory responses. To define the signal transduction pathways activated by MAPKAPK2, we identified potential MAPKAPK2 substrates by using a functional proteomic approach consisting of in vitro phosphorylation of neutrophil lysate by active recombinant MAPKAPK2, protein separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and phosphoprotein identification by peptide mass fingerprinting with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and protein database analysis. One of the eight candidate MAPKAPK2 substrates identified was the adaptor protein, 14-3-3zeta. We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. The chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP) stimulated p38-MAPK-dependent phosphorylation of 14-3-3 proteins in human neutrophils. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3zeta at Ser-58. Computational modeling and calculation of theoretical binding energies predicted that both phosphorylation at Ser-58 and mutation of Ser-58 to Asp (S58D) compromised the ability of 14-3-3zeta to dimerize. Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1. These data suggest that MAPKAPK2-mediated phosphorylation regulates 14-3-3zeta functions, and this MAPKAPK2 activity may represent a novel pathway mediating p38 MAPK-dependent inflammation.
[The antiproteinuric action of angiotensin-converting enzyme inhibitors in chronic glomerulonephritis and diabetic nephropathy]. (1994)

Antiproteinuria effects of angiotensin-converting enzyme (ACE) inhibitors was studied in 23 patients with chronic nephritis (CN) and 32 patients with diabetic nephropathy (DN). CN patients received Capoten, DN patients were given enalapril. The drugs were also examined for the action on systemic arterial pressure, renal function and intrarenal hemodynamics. Significantly decreased urinary excretion of protein occurred in DN patients on the treatment month 1, in CN subjects on month 3. In both groups ACE inhibitors produced marked hypotensive effect, did not affect renal function, noticeably improved intraglomerular hemodynamics. Hypotensive and antiproteinuria activity of the drugs were unrelated. The mechanism of antiproteinuria action of ACE inhibitors works via normalization of intrarenal hemodynamics. Systemic arterial hypertension seems to be an additional factor aggravating disturbances of intrarenal circulation and provoking proteinuria.
A resonant terahertz detector utilizing a high electron mobility transistor (2002)

We report on the implementation of a terahertz detector utilizing two-dimensional electronic fluid in a high electron mobility transistor. The device response is compared with the predictions of the hydrodynamic theory of electronic fluid. The results indicate the viscosity of electronic fluid might be larger than estimated previously. We also report on the unusual polarization dependence of the detector response.
Identification of Two Glycoforms of the MUC5B Mucin in Human Respiratory Mucus (1997)

It has been demonstrated previously that respiratory secretions contain three oligomeric, gel-forming mucins; one of these was identified as the product of the MUC5AC gene (1). Here we demonstrate that the other two mucins are glycoforms of the MUC5B gene product. This was accomplished by trypsin treatment of the purified reduced mucin subunit populations and N-terminal sequencing of the liberated peptides. The products of trypsin digestion were separated by gel filtration into high molecular weight mucin glycopeptides and low molecular weight tryptic peptides. The latter were fractionated by reverse phase chromatography, and four of the major peptides were sequenced. Three of these peptides were identical to and contiguous within a 51-amino acid sequence deduced from a cDNA clone (JER57) encoding a portion of the MUC5B mucin. The other peptide is also present within this sequence but showed identity in only 9 of its 10 residues. A polyclonal antiserum raised against one of these peptides was reactive with the two putative MUC5B glycoforms. Analysis of the high molecular weight glycopeptides indicated that the MUC5B subunit contained different types and lengths of glycosylated domains; one domain of Mr 7.3 x 10(5), two domains of Mr 5.2 x 10(5), and a third domain of Mr 2.0 x 10(5). The amino acid composition of the larger two glycopeptides was similar in serine, threonine, and proline content but distinct from that of the smallest glycopeptide. Each of these domains in the mucin subunit is separated by a trypsin-sensitive region, and the relative abundance of the major peptides derived by proteolysis of these regions and their occurrence in a contiguous sequence suggest that they contain a common cysteine-rich motif.
Regiospecific alkylation of cyclic .beta.-diketone enol ethers. General synthesis of 4-alkylcyclohexenones (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleRegiospecific alkylation of cyclic .beta.-diketone enol ethers. General synthesis of 4-alkylcyclohexenonesGilbert Stork and Rick L. DanheiserCite this: J. Org. Chem. 1973, 38, 9, 1775–1776Publication Date (Print):May 1, 1973Publication History Published online1 May 2002Published inissue 1 May 1973https://doi.org/10.1021/jo00949a048RIGHTS & PERMISSIONSArticle Views4379Altmetric-Citations245LEARN 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 InReddit PDF (206 KB) Get e-Alerts Get e-Alerts
Involvement of the Actin Cytoskeleton and Homotypic Membrane Fusion in ER Dynamics inCaenorhabditis elegans (2005)

The endoplasmic reticulum (ER) is the major intracellular membrane system. The ER is essential for protein and lipid biosynthesis, transport of proteins along the secretory pathway, and calcium storage. Here, we describe our investigations into the dynamics and regulation of the ER in the early Caenorhabditis elegans embryo. Using a GFP fusion to the ER-resident signal peptidase SP12, we observed the morphological transitions of the ER through fertilization and the early cell-cycles in living embryos. These transitions were tightly coordinated with the division cycle: upon onset of mitosis, the ER formed structured sheets that redispersed at the initiation of cleavage. Although microtubules were not required for the transition of the ER between these different states, the actin cytoskeleton facilitated the dispersal of the ER at the end of mitosis. The ER had an asymmetric distribution in the early embryo, which was dependent on the establishment of polarity by the PAR proteins. The small GTPase ARF-1 played an essential role in the ER dynamics, although this function appeared to be unrelated to the role of ARF-1 in vesicular traffic. In addition, the ER-resident heat shock protein BiP and a homologue of the AAA ATPase Cdc48/p97 were found to be crucial for the ER transitions. Both proteins have been implicated in homotypic ER membrane fusion. We provide evidence that homotypic membrane fusion is required to form the sheet structure in the early embryo.
Intracerebral tetracycline-dependent regulation of gene expression in grafts of neural precursors (1996)

Tight control of the activity of a therapeutic gene introduced in vivo is a major issue in gene therapy research. Appropriate levels of expression may be crucial for gene correction. The tetracycline-sensitive regulatory system is highly effective for transcriptional regulation of foreign genes in mammalian cells. Here we report tight tetracycline-dependent regulation of a luciferase reporter gene transferred into the rat brain in the genetically modified neural precursor cell line ST14A as early as 2 days and until at least 6 days after transplantation. This is the first demonstration of the potential of this regulatory system for the modulation of the expression of therapeutic genes introduced into the central nervous system.
The Role of Prostaglandins in Bone Formation (1995)

Prostaglandins of the E series have been shown to be effective inducers of bone formation in vivo. In this study, the effects of PGE2 were evaluated in vivo using subcutaneous administration (3 mg/kg/d for 25 days) to ovariectomized rats or local application in the marrow cavity of tibiae of rats using biodegradable implants (0.13, 1.4 and 32 microg released over 8 days). Systemic treatment of rats with PGE2 stimulated cancellous bone formation in the metaphysis of the proximal tibiae as well as endocortical bone formation and de novo trabecular bone formation in the marrow cavity. Local delivery of PGE2 increased cancellous bone volume in the secondary spongiosa and cortical thickness (at 32 microg). Comparisons of prostanoid effects in vitro, in a bone-derived cell line, showed that PGF2alpha was a better stimulator of DNA synthesis than PGE2. PGF2alpha increased the steady state levels of IGF-I receptor mRNA while PGE2 increased IGF-I expression. Although the mechanism of bone formation by PGE2 is not known at this time, it is clear that PGE2 has powerful local anabolic effects on bone formation in vivo possibly by mediating responses to signals such as changes in mechanical force.
Highly Effective Recombinant Format of a Humanized IgG-like Bispecific Antibody for Cancer Immunotherapy with Retargeting of Lymphocytes to Tumor Cells (2007)

We previously reported the marked in vitro and in vivo antitumor activity of hEx3, a humanized diabody (small recombinant bispecific antibody) with epidermal growth factor receptor (EGFR) and CD3 retargeting. Here, we fabricated a tetravalent IgG-like bispecific antibody with two kinds of single-chain Fv (scFv), i.e. humanized anti-EGFR scFv and anti-CD3 scFv, that contains the same four variable domains as hEx3, on the platform of human IgG1 (hEx3-scFv-Fc). hEx3-scFv-Fc prepared from mammalian cells showed specific binding to both EGFR and CD3 target antigens. At one-thousandth (0.1-100 fmol/ml) of the dose of normal hEx3, hEx3-scFv-Fc showed intense cytotoxicity to an EGFR-positive cell line in a growth-inhibition assay using lymphokine-activated killer cells with the T-cell phenotype (T-LAK cells). The enhanced antitumor effect was more clearly observed when peripheral blood mononuclear cells (PBMCs) were used as effector cells, indicating the utility of IgG-like fabrication. These results suggested that the intense antitumor activity is attributable to the multivalency and the presence of the fused human Fc, a hypothesis that was supported by the results of flow cytometry, PBMC proliferation assay, and protein kinase inhibition assay. Furthermore, the growth inhibition effects of hEx3-scFv-Fc were considerably superior to those of the approved therapeutic antibody, cetuximab, which recognizes the same EGFR antigen even when using PBMCs as effector cells. The high potency of hEx3-scFv-Fc may translate into improved antitumor therapy and lower costs of production because of the smaller doses needed.
꾸지뽕 열매의 일반성분 비교 (2015)

This study was performed in order to use the Curdrania tricuspidata Bureau fruit as new source of natural food colorant. First of all, the proximate compositions of C. tricuspidata bureau fruit was investigated. Moisture, crude protein, crude fat, and crude ash contents of C. tricuspidata bureau fruit were 76.51, 2.17, 1.09, and 3.54%, respectively. Hunter colors of C. tricuspidata bureau fruit showed L value 19.48, a value 23.31, and b value 10.41. pH, titratable acidity, and soluble solid contents of those were 6.05, 0.31%, and 17.73 °Brix, respectively. Total dietary fiber content of C. tricuspidata bureau fruit produced in Edenkujibbong Nongwon was higher 9.46±2.67% than those of other regions (3.49±0.57∼6.10±0.95%). Potassium (K) content was the highest 5,845.00 mg/100 g in mineral. Alanine content was the highest 22.41±0.19 mg/kg in free amino acid. Results suggest that C. tricuspidata Bureau fruit could be used as resources for natural coloring agent.