gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Biological Activity of a Difluoro-Substituted, Conformationally Rigid Vigabatrin Analogue as a Potent γ-Aminobutyric Acid Aminotransferase Inhibitor (2003)

Previously it was found that a conformationally rigid analogue (2) of the epilepsy drug vigabatrin (1) did not inactivate gamma-aminobutyric acid aminotransferase (GABA-AT). A cyclic compound with an exocyclic double bond (6) was synthesized and was found to inactivate GABA-AT, but only in the absence of 2-mercaptoethanol. The corresponding difluoro-substituted analogue (14) was synthesized and was shown to be a very potent time-dependent inhibitor, even in the presence of 2-mercaptoethanol.
Novel inhibitors of prolyl 4-hydroxylase. 5. The intriguing structure-activity relationships seen with 2,2'-bipyridine and its 5,5'-dicarboxylic acid derivatives (1993)

Members of a series of 2,2'-bipyridines have been synthesized and tested as inhibitors of prolyl hydroxylase (EC 1.14.11.2). The structure-activity relationships seen with [2,2'-bipyridine]-5-carboxylic acid (4) closely resemble those of pyridine-2-carboxylic acid (2). Accordingly, [2,2'-bipyridine]-5,5'-dicarboxylic acid (11, IC50 = 0.19 microM) is the most potent inhibitor of its type yet reported. However, 2,2'-bipyridines lacking a 5-carboxylate are poor inhibitors. These contrasting structure-activity relationships are discussed in terms of net anionic charge, iron chelation, and the availability of alternative putative binding modes at a single binding site in each catalytic subunit.
Search for Chiral Catalysts Through Ligand Diversity: Substrate‐Specific Catalysts and Ligand Screening on Solid Phase (1997)

An efficient strategy in the search for chiral catalysts is ligand optimization on solid support. This diversity approach provides unique opportunities for the identification of substrate-specific catalysts and leads to the discovery of ligands with unusual properties that might have otherwise escaped detection. Thus, addition of TMSCN to cyclopentene oxide with ligands 1 or 2, which are very similar, results in opposite enantioselectivities (see reaction on the right; TMS = trimethylsilyl).
Thrombopoiesis-stimulating factor: its effects on megakaryocyte colony formation in vitro and its relation to human granulocyte-macrophage colony-stimulating factor. (1990)

The effects of thrombopoiesis-stimulating factor (TSF) on human marrow megakaryocyte colony formation in vitro were studied by the plasma clot method. TSF was found to stimulate megakaryocyte as well as granulocyte-macrophage colony formation in vitro at optimal concentrations of 200-300 pg/ml of medium containing 2.5% horse serum. This colony-stimulating effect of TSF was not affected by polyclonal antibodies to human (h) interleukin 3 (IL-3) or to granulocyte colony-stimulating factor (G-CSF) but was neutralized by monoclonal or polyclonal antibodies to human granulocyte-macrophage colony-stimulating factor (hGM-CSF). In order to differentiate among cross-reactivity between TSF and hGM-CSF, induction of colony growth via release of GM-CSF, and presence of hGM-CSF in TSF preparations, TSF was tested on murine marrow cells, which are not responsive to hGM-CSF. TSF induced growth of murine megakaryocyte colony-forming units (CFU-MK) and granulocyte-macrophage colony-forming units (CFU-GM) in vitro with a dose response similar to that observed on human marrow cells; however, this effect could not be neutralized by antibodies to either human or murine GM-CSF. Using a double-antibody enzyme-linked immunosorbent assay, TSF preparations were found to contain 36 +/- 4 U of hGM-CSF per picogram of TSF protein. These findings indicate that hGM-CSF is responsible for the megakaryocyte colony-promoting effects of TSF on human marrow cells in vitro.
A phase 1 study of MORAb-009, a monoclonal antibody against mesothelin in pancreatic cancer, mesothelioma and ovarian adenocarcinoma (2007)

14041 Background: MORAb-009 is a monoclonal antibody that targets mesothelin, a cell surface adhesive protein overexpressed in pancreatic, ovarian, non-small cell lung carcinomas and mesothelioma and has minimal expression in normal tissue. The target is over-expressed by tumor cells. It was identified as one of the most prominent, differentially expressed cell surface antigens on pancreatic adenocarcinoma using SAGE of primary tumors vs. normal pancreatic tissue. In vitro studies show MORAb-009 to be effective in mediating cell killing by ADCC and inhibiting cell adhesion.. In xenograft models, MORAb-009 has single agent anti-tumor activity enhanced by the addition of chemotherapy. Toxicology studies show no toxicity in non-human primates and no significant binding to non-tumor tissues. Methods: Sequential cohorts of 3 patients received MORAb-009 intravenously on days 1, 8, 15 and 22 at doses of 12.5, 25, 50 and 100 mg/m 2 . Major inclusion criteria are the presence of a mesothelin-positive tumor with progression on primary therapy, acceptable organ function, ECOG PS 0–2, and measurable disease by CT. Safety pharmacology studies include chemistry, hematology, urinalysis and EKG. Tumors were re-imaged at day 35. Results: 11 patients have received MORAb-009 at doses up to 100 mg/m 2 . 6 patients had mesothelioma, 3 had pancreatic cancer and 2 had mesothelin-positive ovarian cancer. 4 patients exhibited grade 1 (3) or 2 (1) infusion reactions; no dose limiting toxicity was observed. A subject in the 50 mg/m 2 cohort with pancreatic cancer who progressed on gemcitabine showed stable disease by CT and a drop in CA 19/9. Based on the response, this patient continues on extended MORAb-009 therapy. Enrollment to the final cohort of 200mgs/m 2 is ongoing, as are pharmacokinetic and anti-MORAb-009 antibody analysis. Conclusion: MORAb-009, a monoclonal antibody against mesothelin is safe and well tolerated at doses up to 100 mg/m 2 . One subject with previously progressive pancreatic cancer had disease stabilization. In light of the positive preclinical data and safe clinical profile, this study supports further evaluation of the efficacy of MORAb-009 in mesothelin-positive tumors. No significant financial relationships to disclose.
Mutational Analysis of 26 Residues of Vaccinia DNA Topoisomerase Identifies Ser-204 as Important for DNA Binding and Cleavage (1997)

Vaccinia DNA topoisomerase, a 314 amino acid type I enzyme, catalyzes the cleavage and rejoining of DNA strands through a DNA-(3'-phosphotyrosyl)-enzyme intermediate formed at a specific target sequence, 5'-(C/T)CCTT downward arrow. To identify amino acids that participate in the DNA binding and transesterification steps, we introduced alanine substitutions at 18 positions within a centrally located 27 amino acid segment (181-RLYKPLLKLTDDSSPEEFLFNKLSERK-207) and at 8 positions near the N-terminus (1-MRALFYKDGK-10). All mutant proteins except two displayed wild-type activity in relaxing supercoiled DNA. F200A and S204A exhibited reduced rates of relaxation and were subjected to a kinetic analysis of the strand cleavage reaction under single-turnover and equilibrium conditions. The F200A and S204A mutations reduced the rate of single-turnover DNA cleavage by factors of 5 and 70, respectively. Both mutations shifted the cleavage-religation equilibrium in favor of the noncovalently bound state. The S204A mutation reduced the affinity of topoisomerase for CCCTT-containing DNA, but did not alter the site-specificity of DNA cleavage. Vaccinia residue Ser-204, which is conserved in all poxvirus topoisomerases, but not in the cellular homologues, may contribute to the unique cleavage site specificity of the poxvirus enzymes. Phe-200 is conserved in all members of the type IB topoisomerase family.
High-Index-Contrast, Wide-FSR Microring-Resonator Filter Design and Realization with Frequency-Shift Compensation (2005)

Rigorous electromagnetic simulations are used to design high-index-contrast microring-resonator filters. The first fabricated third-order filters compensated for passband distortion due to coupling-induced and fabrication-related frequency shifts demonstrate a 20nm FSR and the highest reported thru-port extinction (14dB).
Sequence-targeted photosensitized reactions in nucleic acids by oligo-.alpha.-deoxynucleotides and oligo-.beta.-deoxynucleotides covalently linked to proflavin (1988)

Proflavin was covalently linked to the 3'-end or to the 5'-end of an octadeoxythymidylate. This oligonucleotide was synthesized with either the natural beta-anomer of thymidine or its synthetic alpha-anomer. A polymethylene chain was used to link one of the amino groups of proflavin to a terminal thiophosphate group of the oligonucleotide. A 27-mer oligodeoxynucleotide containing an octadeoxyadenylate sequence was used as a target for the proflavin-substituted octadeoxythymidylates. Upon irradiation with visible light, photo-cross-linking reactions induced the formation of branched species that migrated more slowly than the 27-mer on denaturing polyacrylamide gels. Piperidine treatment of the photo-cross-linked species induced strand breaks in the 27-mer. In addition, proflavin induced photosensitized reactions at guanine residues in the 27-mer sequence which were converted to strand breaks following piperidine treatment. Triple-helix formation by the oligothymidylates with their complementary oligodeoxyadenylate sequence at high salt concentration led to photo-cross-linking and cleavage reactions on both sides of the target sequence. These results show that it is possible to target photosensitized reactions to specific sequences on nucleic acids. This opens new possibilities for site-directed mutagenesis and the development of photoactive anti-messenger oligodeoxynucleotides.
Detection of asymptomatic herpes simplex virus infections after vaccination (1987)

Twenty-two volunteers seronegative for antibodies to herpes simplex virus (HSV) were enrolled in a trial to determine tolerance and immunogenicity of an HSV-2 glycoprotein subunit vaccine. Vaccine was administered at days 0, 28, and 140, and sera were obtained on days 0, 7, 14, 21, 28, 35, 49, 56, 140, 147, and 365 for determination of HSV neutralizing antibody activity and antibody-dependent cell cytotoxicity (ADCC). Sera were also tested by immunoprecipitation of radiolabeled HSV-2-infected cell proteins and polyacrylamide gel electrophoresis to identify the viral proteins which elicited antibody responses in vaccine recipients. After vaccination two male volunteers presented with atypical first-episode genital herpes: patient 1 with a culture-negative genital lesion at day 53 and patient 3 with urethritis at day 68. Seroconversion to wild-type viral proteins not present in the vaccine was detectable by radioimmunoprecipitation-polyacrylamide gel electrophoresis within 10 days in both patients. Two additional volunteers, one a sex contact of patient 1, seroconverted asymptomatically to nonvaccine proteins during the trial. All four vaccine breakthrough patients were indistinguishable from the other volunteers in the time required to develop neutralizing and ADCC antibodies, in the titer of these antibodies, and the time to seroconversion to gB and gD vaccine proteins. However, only one of the four breakthrough patients had antibodies to g80 (a complex of gC-2 and gE) after vaccination as compared with 15 of the other 18 volunteers (P = 0.05). Neither neutralizing antibody nor ADCC titers consistently identified acquisition of wild-type viral infection; therefore, protein-specific serologies were required to detect wild-type antibodies in these four patients. These data underscore the importance of using serologic assays which will distinguish naturally acquired infection from the immune response to vaccination.
Possible mechanism of inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid: nucleoside conjugate. (1988)

As described previously (I. Kijima-Suda et al., Cancer Res., 46: 858-862, 1986), a sialyltransferase inhibitor, 5-fluoro-2',3'-isopropylidene-5'-O-(4-N-acetyl-2,4-dideoxy-3,6,7,8-tetra -O- acetyl-1-methoxycarbonyl-D-glycero-alpha-D-galactooctapyranosyl)ur idine (KI-8110), inhibits pulmonary metastasis of murine colon adenocarcinoma 26 sublines of high (NL-17) and low (NL-44) metastatic potential. To investigate the mechanism of this inhibition, the effect of KI-8110 on the metastatic cascade, especially on the interaction between tumor cells and platelets which may play a crucial role in tumor cell metastasis, was examined. NL-17 cells induced irreversible platelet aggregation in heparinized human platelet-rich plasma in vitro. This activity was reduced by pretreatment of the tumor cells with KI-8110. Inhibition of aggregation was also induced by the treatment of tumor cells with neuraminidase or Limax flavus agglutinin, a lectin specific for sialic acid. Sialic acid, fucose, sialyllactose, and bovine submaxillary mucin inhibited this tumor cell-induced platelet aggregation, while galactose, mannose, lactose, alpha 1-acid glycoprotein, fetuin, and asialo-bovine submaxillary mucin did not. KI-8110 also inhibited platelet-derived growth factor-dependent growth of NL-17 cells, but showed no effect on insulin or epidermal growth factor-dependent growth of the tumor cells. Platelet-derived growth factor-induced phosphorylation of membrane protein was reduced by treatment of NL-17 cells with KI-8110. The same result was obtained in the neuraminidase-treated membrane fraction of NL-17 cells. These results suggest that KI-8110 inhibits experimental tumor cell metastasis by inhibiting the interaction between tumor cells and host platelets in at least two pathways, and this may be due to a reduction of sialic acid contents of the membrane surface of tumor cells.
Vav Family Proteins Couple to Diverse Cell Surface Receptors (2000)

Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple with similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation. Integrin-induced tyrosine phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT-dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NFkappaB-dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways.
Respiratory Viruses in Nepalese Children With and Without Pneumonia (2010)

All of the 7 respiratory viruses were associated with pneumonia, but their pathogenicity varied. Parainfluenza type 3, RSV, and influenza A were most strongly associated with pneumonia.
Metabotropic Glutamate Receptors Activate G-Protein-Coupled Inwardly Rectifying Potassium Channels inXenopusOocytes (1996)

Receptor-mediated activation of a G-protein-coupled inwardly rectifying potassium channel (GIRK) is a common mechanism for synaptic modulation in the CNS. However, evidence for metabotropic glutamate receptor (mGluR) activation of GIRK is virtually nonexistent, despite the widespread and overlapping distribution of these proteins. We examined this apparent paradox by coexpressing mGluRs 1a, 2, and 7 with the GIRK subunits Kir3.1 and Kir3.4 in Xenopus oocytes. Functional expression of GIRK was confirmed by coexpression with the D2 dopamine receptor that is known to activate GIRK in neurons. Agonist activation of each of the three mGluRs evoked inward potassium currents in symmetrical KCI solutions. The current amplitudes evoked by mGluR1a, mGluR2, and D2 were comparable, whereas mGluR7 currents were somewhat smaller. mGluR1a-evoked GIRK currents were not blocked in BAPTA-treated oocytes, demonstrating that GIRK activation was distinct from phospholipase C-mediated activation of the endogenous calcium-dependent chloride current (lCaCl). Pertussis toxin (PTX) treatment significantly reduced both the mGluR and D2 receptor-evoked GIRK currents. In oocytes in which mGluR2 and D2 were coexpressed, activation of mGluR2 occluded additional D2 receptor current, indicating that mGluR2 and D2 receptor coupling to GIRK involves a common G-protein. The efficient coupling of mGluRs to GIRK in oocytes suggests either that mGluR activation of GIRK has been overlooked in neurons or possibly that mGluRs are excluded from GIRK-containing microdomains.
Mass transfer of macromolecules in steric exclusion chromatography. 2. Convective transport in internal pores (hydrodynamic chromatography) (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMass transfer of macromolecules in steric exclusion chromatography. 2. Convective transport in internal pores (hydrodynamic chromatography)Matthias Grueneberg and Joachim KleinCite this: Macromolecules 1981, 14, 5, 1415–1419Publication Date (Print):September 1, 1981Publication History Published online1 May 2002Published inissue 1 September 1981https://pubs.acs.org/doi/10.1021/ma50006a052https://doi.org/10.1021/ma50006a052research-articleACS PublicationsRequest reuse permissionsArticle Views43Altmetric-Citations3LEARN 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
A revision of the genus Trichoderma. I. Section Longibrachiatum sect. nov. (1984)

Variation in strains assignable to the Trichoderma longibrachiatum Rifai and T. pseudokoningii Rifai species aggregates was studied. Morphological similarities allow their assignment to one section in Trichoderma, sect. Longibrachiatum, characterized and differentiated from other species of Trichoderma by the sparsely branched conidiophores having a high proportion of solitary phialides. Cultural characteristics include very rapid growth and the production of characteristic bright yellow-green pigments visible in the colony reverse. Two new species are described in the section: Trichoderma citrinoviride Bissett has ellipsoidal conidia smaller than in the other species and conidiophore branching similar to that in T. pseudokoningii; Trichoderma atroviride Bissett has relatively large, ellipsoidal conidia and a very sparse branching system with curved or sinuous conidiophores, branches, and phialides.
Effect of product form, compaction, vibration and comminution on energywood bulk density (1995)

A study was performed to examine the changes in density of stacked roundwood, chips, and chunks as affected by various compaction treatments. Density of stacked roundwood bolts was tested for the effect of stacking orientation, binding of the stack ends, and species. Stacked bolt wood occupied less than 50 percent of the total rack space for all species, giving final dry bulk densities, based on total rack volume, of 159 to 293 kg/m3. Alternating butt ends in the rack increased final bulk densities by an average of approximately 40 percent. The effect was greatest for mixed, small hardwood stems. Vibration and compaction of chipped material (pine, mixed hardwood, and sycamore) resulted in final dry bulk densities of from 170 to 273 kg/m3. Vibration increased dry bulk density by an average of 20 percent, whereas compaction increased dry bulk density by about 30 percent, vibration of sycamore chunks produced a 17 percent increase.
Nitrolinoleic acid: An endogenous peroxisome proliferator-activated receptor γ ligand (2005)

Nitroalkene derivatives of linoleic acid (nitrolinoleic acid, LNO2) are formed via nitric oxide-dependent oxidative inflammatory reactions and are found at concentrations of approximately 500 nM in the blood of healthy individuals. We report that LNO2 is a potent endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARgamma; Ki approximately 133 nM) that acts within physiological concentration ranges. This nuclear hormone receptor (PPARgamma) regulates glucose homeostasis, lipid metabolism, and inflammation. PPARgamma ligand activity is specific for LNO2)and not mediated by LNO2 decay products, NO donors, linoleic acid (LA), or oxidized LA. LNO2 is a significantly more robust PPARgamma ligand than other reported endogenous PPARgamma ligands, including lysophosphatidic acid (16:0 and 18:1), 15-deoxy-Delta12,14-PGJ2, conjugated LA and azelaoyl-phosphocholine. LNO2 activation of PPARgamma via CV-1 cell luciferase reporter gene expression analysis revealed a ligand activity that rivals or exceeds synthetic PPARgamma agonists such as rosiglitazone and ciglitazone, is coactivated by 9 cis-retinoic acid and is inhibited by the PPARgamma antagonist GW9662. LNO2 induces PPARgamma-dependent macrophage CD-36 expression, adipocyte differentiation, and glucose uptake also at a potency rivaling thiazolidinediones. These observations reveal that NO-mediated cell signaling reactions can be transduced by fatty acid nitration products and PPAR-dependent gene expression.
Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation (2004)

Previous reports showed the therapeutic effect of transplants of bone marrow stromal cells (BMSC) after incomplete traumatic spinal cord lesions. We studied the effect of this form of therapy in chronically paraplegic Wistar rats due to severe spinal cord injury (SCI). Rats were subjected to weight-drop impact causing paraplegia, and BMSC or phosphate buffered saline (PBS) was injected into spinal cord 3 months after injury. Functional outcome was measured using the Basso-Beattie-Bresnehan score until sacrifice of the animals, 4 weeks after transplantation. At this time, samples of spinal cord tissue were studied histologically. The results showed a clear and progressive functional recovery of the animals treated with BMSC transplantation, compared to controls. Grafted BMSC survived into spinal cord tissue, forming cell bridges within the traumatic centromedullary cavity. In this tissue, cells expressing neuronal and astroglial markers can be seen, together with a marked ependymal proliferation, showing nestin-positivity. These findings suggest the utility of BMSC transplantation in chronically established paraplegia.