gebhart/patrepeval huggingface dataset:
Inhibition of myeloperoxidase by salicylhydroxamic acid (1989)

Salicylhydroxamic acid inhibited the luminol-dependent chemiluminescence of human neutrophils stimulated by phorbol 12-myristate 13-acetate or the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). This compound had no inhibitory effect on the kinetics of O2.- generation or O2 uptake during the respiratory burst, but inhibited both the peroxidative activity of purified myeloperoxidase and the chemiluminescence generated by a cell-free myeloperoxidase/H2O2 system. The concentration of salicylhydroxamic acid necessary for complete inhibition of myeloperoxidase activity was 30-50 microM (I50 values of 3-5 microM) compared with the non-specific inhibitor NaN3, which exhibited maximal inhibition at 100-200 microM (I50 values of 30-50 microM). Whereas taurine inhibited the luminol chemiluminescence of an H2O2/HOC1 system by HOC1 scavenging, this compound had little effect on myeloperoxidase/H2O2-dependent luminol chemiluminescence; in contrast, 10 microM-salicylhydroxamic acid did not quench HOC1 significantly but greatly diminished myeloperoxidase/H2O2-dependent luminol chemiluminescence, indicating that its effects on myeloperoxidase chemiluminescence were largely due to peroxidase inhibition rather than non-specific HOC1 scavenging. Salicylhydroxamic acid prevented the formation of myeloperoxidase Compound II, but only at low H2O2 concentrations, suggesting that it may compete for the H2O2-binding site on the enzyme. These data suggest that salicylhydroxamic acid may be used as a potent inhibitor to delineate the function of myeloperoxidase in neutrophil-mediated inflammatory events.
A Proline-Rich Motif within the Matrix Protein of Vesicular Stomatitis Virus and Rabies Virus Interacts with WW Domains of Cellular Proteins: Implications for Viral Budding (1999)

The matrix (M) protein of rhabdoviruses has been shown to play a key role in virus assembly and budding; however, the precise mechanism by which M mediates these processes remains unclear. We have associated a highly conserved, proline-rich motif (PPxY or PY motif, where P denotes proline, Y represents tyrosine, and x denotes any amino acid) of rhabdoviral M proteins with a possible role in budding mediated by the M protein. Point mutations that disrupt the PY motif of the M protein of vesicular stomatitis virus (VSV) have no obvious effect on membrane localization of M but instead lead to a decrease in the amount of M protein released from cells in a functional budding assay. Interestingly, the PPxY sequence within rhabdoviral M proteins is identical to that of the ligand which interacts with WW domains of cellular proteins. Indeed, results from two in vitro binding assays demonstrate that amino acids 17 through 33 and 29 through 44, which contain the PY motifs of VSV and rabies virus M proteins, respectively, mediate interactions with WW domains of specific cellular proteins. Point mutations that disrupt the consensus PY motif of VSV or rabies virus M protein result in a significant decrease in their ability to interact with the WW domains. These properties of the PY motif of rhabdovirus M proteins are strikingly analogous to those of the late (L) budding domain identified in the gag-specific protein p2b of Rous sarcoma virus. Thus, it is possible that rhabdoviruses may usurp host proteins to facilitate the budding process and that late stages in the budding process of rhabdoviruses and retroviruses may have features in common.
Purification of the sodium- and chloride-coupled glycine transporter from central nervous system. (1991)

We have recently developed a reconstitution assay which allows the rapid determination of sodium- and chloride-dependent glycine transport activity of many fractions (López-Corcuera, B., and Aragón, C. (1989) Eur. J. Biochem. 181, 519-524). In this paper we report the purification of the sodium- and chloride-coupled glycine transporter from pig brain stem. Transporter is solubilized from plasma membrane vesicles with 2% cholate and purified by sequential chromatography on phenyl-Sepharose, wheat germ agglutinin-Sepharose, and hydroxylapatite columns, followed by a 5-20% sucrose density gradient fractionation. Taking into account the inactivation suffered by the transporter, a final increase in specific activity of about 450-fold is achieved. Although two polypeptides with apparent molecular masses of 100 and 37 kDa are progressively enriched during the chromatographic steps, only the 100-kDa band comigrates with transport activity along the density gradient. This band is finally isolated to apparent homogeneity in the active fractions. We conclude that the 100-kDa band represents the glycine transporter. Finally, the pure transporter can be reconstituted into liposomes, retaining the absolute dependence on sodium and chloride gradients, the electrogenicity, the glycine affinity, the substrate specificity, and the sensitivity to group-selective modifiers characteristic of the native transporter.
Isolation of Fluorescent Pseudomonads with a Selective Medium (1970)

Incorporation of novobiocin, penicillin, and cycloheximide into a standard medium for fluorescence selects for fluorescent pathogenic and free-living pseudomonads.
Determination of Alkoxyl Groups by Nonaqueous Titration (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of Alkoxyl Groups by Nonaqueous TitrationR. H. Cundiff and P. C. MarkunasCite this: Anal. Chem. 1961, 33, 8, 1028–1030Publication Date (Print):July 1, 1961Publication History Published online1 May 2002Published inissue 1 July 1961https://pubs.acs.org/doi/10.1021/ac60176a049https://doi.org/10.1021/ac60176a049research-articleACS PublicationsRequest reuse permissionsArticle Views76Altmetric-Citations7LEARN 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
Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours (1997)

This is the first study to describe the association between expression of MUC1 and MUC2 mucins and prognosis in ovarian cancer. Paraffin sections of epithelial ovarian tumours (n = 182: 29 benign, 21 low malignant potential, and 132 invasive tumours) were analysed immunohistochemically for expression of MUC1 and MUC2 mucin core proteins. Most benign, low malignant potential, and invasive tumours showed high MUC1 expression in the cytoplasm. Low cytoplasmic expression of MUC1 was a predictor for good prognosis, particularly within stage III tumours. A minority of benign epithelial tumours, but most low malignant potential and invasive non-mucinous tumours, showed high MUC1 expression on the cell membrane. High apical MUC1 reactivity was associated with non-mucinous tumours. Low expression of MUC1 in the apical membrane was associated with early stage and good outcome for invasive tumours. Most benign and low malignant potential tumours, but only a minority of invasive tumours, showed MUC2 expression. MUC2 was found in non-mucinous as well as in mucinous tumours. The presence of MUC2 was inversely associated with high tumour grade but was not associated with altered survival. These results support experimental evidence that MUC1 influences the metastatic ability of ovarian cancer.
An evaluation of phase I cancer clinical trial designs (1998)

Phase I clinical trials are designed to identify an appropriate dose for experimentation in phase II and III studies. I present the results from a simulation study to evaluate the performance of nine phase I designs involving the standard design, the two-stage modified Storer's design, the two-stage Korn's design, the one-stage modified continual reassessment method (CRM) designs, and the two-stage modified CRM designs. I compare the performance of the above phase I designs in terms of the following criteria: (i) the proportion of the recommended maximum tolerated dose (MTD) at each dose level; (ii) the proportion of patients treated at each dose level; (iii) the average number of patients to complete the trial; (iv) the probability of toxicity observed; and (v) the average number of cohorts to complete the trial. In general, the one-stage modified CRM II and CRM III designs perform well compared with the other designs considered in this study. The one-stage modified CRM II and III designs require much fewer numbers of cohorts than do the two-stage modified CRM II and III designs. The one-stage modified CRM II and III designs avoid the criticisms of the original CRM by reducing the average number of cohorts and toxicity incidences, while estimating the MTD more accurately than does the standard design. © 1998 John Wiley & Sons, Ltd.
Properties of the bioluminescent protein aequorin (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProperties of the bioluminescent protein aequorinOsamu Shimomura and Frank Harris JohnsonCite this: Biochemistry 1969, 8, 10, 3991–3997Publication Date (Print):October 1, 1969Publication History Published online1 May 2002Published inissue 1 October 1969https://pubs.acs.org/doi/10.1021/bi00838a015https://doi.org/10.1021/bi00838a015research-articleACS PublicationsRequest reuse permissionsArticle Views936Altmetric-Citations92LEARN 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
Optimizing Glioblastoma Temozolomide Chemotherapy Employing Lentiviral-based Anti-MGMT shRNA Technology (2013)

Despite treatments combining surgery, radiation-, and chemotherapy, patients affected by glioblastoma (GBM) have a limited prognosis. Addition of temozolomide (TMZ) to radiation therapy is the standard therapy in clinical application, but effectiveness of TMZ is limited by the tumor's overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). The goal of this study was to use the highly specific and efficient RNA interference (RNAi) pathway to modulate MGMT expression to increase TMZ efficiency in chemotherapy resistant GBM. Using lentiviral-based anti-MGMT small hairpin RNA (shRNA) technology we observed a specific inhibition of the MGMT expression in GBM cell lines as well as in subcutaneous tumors. Tumor growth inhibition was observed following TMZ treatment of xenografts with low MGMT expression in contrast to xenografts with high MGMT expression. Bioluminescence imaging (BLI) measurements indicated that luciferase and shRNA-expressing lentiviruses were able to efficiently transduce the GBM xenografts in vivo. Treatment combining injection of a lentivirus expressing an anti-MGMT shRNA and TMZ induced a reduction of the size of the tumors, in contrast with treatment combining the lentivirus expressing the control shRNA and TMZ. Our data suggest that anti-MGMT shRNA therapy could be used in combination with TMZ chemotherapy in order to improve the treatment of resistant GBM.
Mapping the Position of DNA Polymerase-Bound DNA Templates in a Nanopore at 5 Å Resolution (2009)

DNA polymerases are molecular motors that catalyze template-dependent DNA replication, advancing along template DNA by one nucleotide with each catalytic cycle. Nanopore-based measurements have emerged as a single molecule technique for the study of these enzymes. Using the alpha-hemolysin nanopore, we determined the position of DNA templates bearing inserts of abasic (1',2'-dideoxy) residues, bound to the Klenow fragment of Escherichia coli DNA polymerase I (KF) or to bacteriophage T7 DNA polymerase. Hundreds of individual polymerase complexes were analyzed at 5 A precision within minutes. We generated a map of current amplitudes for DNA-KF-deoxynucleoside triphosphate (dNTP) ternary complexes, using a series of templates bearing blocks of three abasic residues that were displaced by approximately 5 A in the nanopore lumen. Plotted as a function of the distance of the abasic insert from n = 0 in the active site of the enzyme held atop the pore, this map has a single peak. The map is similar when the primer length, the DNA sequences flanking the abasic insert, and the DNA sequences in the vicinity of the KF active site are varied. Primer extension catalyzed by KF using a three abasic template in the presence of a mixture of dNTPs and 2',3'-dideoxynucleoside triphosphates resulted in a ladder of ternary complexes with discrete amplitudes that closely corresponded to this map. An ionic current map measured in the presence of 0.15 M KCl mirrored the map obtained with 0.3 M KCl, permitting experiments with a broader range of mesophilic DNA and RNA processing enzymes. We used the abasic templates to show that capture of complexes with the KF homologue, T7 DNA polymerase, yields an amplitude map nearly indistinguishable from the KF map.
Theory of cavity-assisted microwave cooling of polar molecules (2008)

We analyze cavity-assisted cooling schemes for polar molecules in the microwave domain, where molecules are excited on a rotational transition and energy is dissipated via strong interactions with a lossy stripline cavity, as recently proposed by A. Andre et al., Nature Physics 2, 636 (2006). We identify the dominant cooling and heating mechanisms in this setup and study cooling rates and final temperatures in various parameter regimes. In particular we analyze the effects of a finite environment temperature on the cooling efficiency, and find minimal temperature and optimized cooling rate in the strong drive regime. Further we discuss the trade-off between efficiency of cavity cooling and robustness with respect to ubiquitous imperfections in a realistic experimental setup, such as anharmonicity of the trapping potential.
Umbilical cord blood processing using Prepacyte‐CB increases haematopoietic progenitor cell availability over conventional Hetastarch separation (2009)

These results show that PrepaCyte-CB offers superior separation of UCB when compared to Hetastarch.
Study of damage evolutions in composite plates subjected to bending loads using micro-macro analysis (1994)

The purpose of this study is to develop a computer program that will predict the damage progression in composite plates subjected to bending loads. Kwon's micromechanical model is used to compute the smeared effective moduli from the material properties of fiber and matrix as well as to determine stresses at the constituent level. Failure criteria based on micro-stresses are then applied to determine the extent and type of damage that occur in the composite under various loading conditions. The progression of damage throughout the composite until complete failure of the composite can then be simulated using the current computer program. The numerical prediction for a laminated composite plate containing a hole and subjected to a bending load agrees well with the experimental data.
Limits of Adaptive Optics for High‐Contrast Imaging (2005)

The effects of photon noise, aliasing, wavefront chromaticity and scintillation on the point spread function (PSF) contrast achievable with ground based adaptive optics (AO) are evaluated for different wavefront sensing schemes. I show that a wavefront sensor (WFS) based upon the Zernike phase contrast technique offers the best sensitivity to photon noise at all spatial frequencies, while the Shack-Hartmann WFS is significantly less sensitive. In AO systems performing wavefront sensing in the visible and scientific imaging in the near-IR, the PSF contrast limit is set by the scintillation chromaticity induced by Fresnel propagation through the atmosphere. On a 8m telescope, the PSF contrast is then limited to 1e-4 to 1e-5 in the central arcsecond. Wavefront sensing and scientific imaging should therefore be done at the same wavelength, in which case, on bright sources, PSF contrasts between 1e-6 and 1e-7 can be achieved within 1 arcsecond on a 8m telescope in optical/near-IR. The impact of atmospheric turbulence parameters (seeing, wind speed, turbulence profile) on the PSF contrast is quantified. I show that a focal plane wavefront sensing scheme offers unique advantages, and I discuss how to implement it. Coronagraphic options are also briefly discussed.
Advances in Therapeutic Fc Engineering – Modulation of IgG-Associated Effector Functions and Serum Half-life (2016)

Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation. The Fc region can further improve mAbs' efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cell-mediated phagocytosis. Moreover, Fc is the region interacting with the neonatal Fc receptor in a pH-dependent manner that can slow down IgG's degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anticancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce the cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering-based mAbs under clinical trials.
Violations of a new inequality for classical fields (1992)

Two entangled photons incident upon two distant interferometers can give a coincidence counting rate that depends nonlocally on the sum of the phases of the two interferometers. It has recently been shown that experiments of this kind may violate a simple inequality that must be satisfied by any classical or semi-classical field theory. The inequality provides a graphic illustration of the lack of objective realism of the electric field. The results of a recent experiment which violates this inequality and in which the optical path length between the two interferometers was greater than 100 m are briefly described.
Requirement for macrophages in neuronal injury induced by HIV envelope protein gp120 (1992)

HIV-1-related neuronal injury may involve a complex web of viral proteins and cytokines, but neurons themselves are not infected. The HIV envelope protein gp120 has been shown to engender an early increase in neuronal free calcium followed by delayed excitotoxic-like damage, which is prevented by N-methyl-D-aspartate (NMDA) antagonists. In the present study, we found that the injurious effects of gp120 on retinal ganglion cell neurons require the presence of macrophages in mixed neuronal glial cultures of postnatal retina. Within 24 hours of incubation, 20 pM gp120 injured nearly 40% of retinal ganglion cells in cultures containing macrophages and other glial cells, whereas no deleterious effects of gp120 were noted on retinal ganglion cells in cultures depleted of macrophages. Thus, the toxic effect of gp120 on neurons appears to be an indirect one, mediated by activation of macrophages and perhaps other glial cells.
Macromolecular Accessibility of Fluorescent Taxoids Bound at a Paclitaxel Binding Site in the Microtubule Surface (2004)

The macromolecular accessibility of the paclitaxel binding site in microtubules has been investigated using a fluorescent taxoid and antibodies against fluorescein, which cannot diffuse into the microtubule lumen. The formation of a specific ternary complex of microtubules, Hexaflutax (7-O-{N-[6-(fluorescein-4'-carboxamido)-n-hexanoyl]-l-alanyl}paclitaxel) and 4-4-20 IgG (a monoclonal antibody against fluorescein) has been observed by means of sedimentation and electron microscopy methods. The kinetics of binding of the antibody to microtubule-bound Hexaflutax has been measured. The quenching of the observed fluorescence is fast (k+ 2.26 +/- 0.25 x 10(6) m(-1) s(-1) at 37 degrees C), indicating that the fluorescein groups of Hexaflutax are exposed to the outer solvent. The velocity of the reaction is linearly dependent on the antibody concentration, indicating that a bimolecular reaction is being observed. Another fluorescent taxoid (Flutax-2) bound to microtubules has also been shown to be rapidly accessible to polyclonal antibodies directed against fluorescein. A reduced rate of Hexaflutax quenching by the antibody is observed in microtubule-associated proteins containing microtubules or in native cellular cytoskeletons. It can be concluded that the fluorescent taxoids bind to an outer site on the microtubules that is shared with paclitaxel. Paclitaxel would be internalized in a further step of binding to reach the known luminal site, this step being blocked in the case of the fluorescent taxoids. Because the fluorescent ligands are able to induce microtubule assembly, binding to the outer site should be enough to induce assembly by a preferential binding mechanism.