gebhart/patrepeval huggingface dataset:
Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities (2006)

Antigens expressed on malignant cells in the absence of significant expression on normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma (NHL), Hodgkin disease, and multiple myeloma. In addition, solid tumors such as renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma, and glioblastoma express high levels of this antigen. To functionally target CD70-expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to contain human IgG1 constant domains. The engineered antibody retained the binding specificity of the murine parent monoclonal antibody and was shown to induce Fc-mediated effector functions including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis in vitro. Further, administration of this antibody significantly prolonged survival of severe combined immunodeficient (SCID) mice bearing CD70+ disseminated human NHL xenografts. Survival of these mice was dependent upon the activity of resident effector cells including neutrophils, macrophages, and natural killer (NK) cells. These data suggest that an anti-CD70 antibody, when engineered to contain human IgG1 constant domains, possesses effector cell-mediated antitumor activity and has potential utility for anticancer therapy.
Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein (1996)

Proper regulation of chondrocyte differentiation is necessary for the morphogenesis of skeletal elements, yet little is known about the molecular regulation of this process. A chicken homolog of Indian hedgehog (Ihh), a member of the conserved Hedgehog family of secreted proteins that is expressed during bone formation, has now been isolated. Ihh has biological properties similar to those of Sonic hedgehog (Shh), including the ability to regulate the conserved targets Patched (Ptc) and Gli. Ihh is expressed in the prehypertrophic chondrocytes of cartilage elements, where it regulates the rate of hypertrophic differentiation. Misexpression of Ihh prevents proliferating chondrocytes from initiating the hypertrophic differentiation process. The direct target of Ihh signaling is the perichondrium, where Gli and Ptc flank the expression domain of Ihh. Ihh induces the expression of a second signal, parathyroid hormone-related protein (PTHrP), in the periarticular perichondrium. Analysis of PTHrP (-/-) mutant mice indicated that the PTHrP protein signals to its receptor in the prehypertrophic chondrocytes, thereby blocking hypertrophic differentiation. In vitro application of Hedgehog or PTHrP protein to normal or PTHrP (-/-) limb explants demonstrated that PTHrP mediates the effects of Ihh through the formation of a negative feedback loop that modulates the rate of chondrocyte differentiation.
Annexin A2 is critical for embryo adhesiveness to the human endometrium by RhoA activation through F‐actin regulation (2012)

Annexin A2 (ANXA2) is present in vivo in the mid- and late-secretory endometria and is mainly localized in the luminal epithelium. Our aim was to evaluate its function in regulating the human implantation process. With an in vitro adhesion model, constructed to evaluate how the mouse embryo and JEG-3 spheroids attach to human endometrial epithelial cells, we demonstrated that ANXA2 inhibition significantly diminishes embryo adhesiveness. ANXA2 is also implicated in endometrial epithelial cell migration and trophoblast outgrowth. ANXA2 was seen to be linked to the RhoA/ROCK pathway and to regulate cell adhesion. We noted that ANXA2 inhibition significantly reduces active RhoA, although RhoA inactivation does not alter the ANXA2 levels. RhoA inactivation and ROCK inhibition also moderate embryo adhesiveness to endometrial epithelial cells. We corroborated that the induction of constitutively active RhoA partially reverses the effects of ANXA2 inhibition on endometrial adhesiveness. These molecules colocalize on the plasma membrane of endometrial epithelial cells, and a large proportion of ANXA2 and RhoA are colocalized in the F-actin networks. The functional effects of ANXA2 inhibition and RhoA/ROCK inactivation are associated with significant alterations in F-actin organization and its depolymerization. ANXA2 may act upstream of the RhoA/ROCK pathway by regulating F-actin remodeling and is a key factor in human endometrial adhesiveness.
A Record Nine Different Phases (Four Cubic, Two Hexagonal, and One Lamellar Lyotropic Liquid Crystalline and Two Micellar Solutions) in a Ternary Isothermal System of an Amphiphilic Block Copolymer and Selective Solvents (Water and Oil) (1998)

We report on a ternary isothermal system consisting of a poly(ethylene oxide)/poly(propylene oxide) (PEO/PPO) amphiphilic block copolymer, “water”, and “oil” (where “water” and “oil” are selective solvents for the different blocks), which exhibits the richest structural polymorphism ever observed (in equilibrium) in mixtures containing amphiphiles (such as block copolymers, surfactants, or lipids). The microstructure resulting from the self-assembly of the PEO/PPO block copolymer can vary from normal (oil-in-water) micelles in solution, through all types of normal and reverse (water-in-oil) lyotropic liquid crystals (normal micellar cubic, normal hexagonal, normal bicontinuous cubic, lamellar, reverse bicontinuous cubic, reverse hexagonal, reverse micellar cubic), to reverse micelles, as the relative volume fraction of the apolar (“oil”-like) components increases over that of the polar (“water”-like) components. The structure in the liquid crystalline phases has been established with small-angle X-ray scattering; both the normal and the reverse bicontinuous cubic structures are consistent with the Ia3d crystallographic space group (and the Gyroid minimal surface), while the normal and reverse micellar cubic structures are consistent with the Im3m and Fd3m space groups, respectively. The self-assembly of amphiphilic block copolymer in selective solvents described here provides a link between the self-assembly of surfactants in water (and oil/cosurfactant) and the self-assembly of block copolymers in the absence of any solvent. Furthermore, the ability of the PEO/PPO amphiphilic block copolymers to attain diverse microstructures is of great importance to numerous practical applications, especially since such copolymers are commercially available (as poloxamers, Pluronics, or Synperonics).
Dry Etching Technique for Subquarter‐Micron Copper Interconnects (1995)

A dry etching technique for subquarter‐micron Cu interconnects has been developed. A self‐aligned passivation film on sidewalls of Cu lines is formed during etching. The thickness of the sidewall film composed of can be controlled precisely by the composition of the etching gas mixture. The addition of to the etching gas mixture of results in a sidewall film free of chlorine. Therefore, the sidewall film acts to protect Cu from oxidation and corrosion, and sustains the multilayered structure without film peeling during the fabrication process.
Effects of Mipragoside ® on Ocular Allergic Inflammation in the Rabbit (1993)

We evaluated the pharmacodynamic and pharmacokinetic profile of Mipragoside, a monosialoganglioside isopropyl-ester (as 0.5% w/w ophthalmic gel), on allergic inflammation of the eye induced by reverse passive Arthus reaction, on a non-immune mast cell degranulation elicited by compound 48/80 and on ocular inflammation produced by horse serum. Conjunctiva was sensitized by injection of rabbit antisera to bovine proteins and the allergic conjunctivitis was triggered by intravenous administration of bovine gamma globulin. The permeability of the blood-conjunctival barrier was evaluated by a fluorometric method. Compound 48/80 was topically administered at concentration of 50mg/ml and histological analysis of conjunctiva was performed. Horse serum was administered by intravenous injection at different days. The pharmacokinetic profile of topical 3H-Mipragoside on 48/80 model was investigated and compared with untreated animals. Mipragoside treatment significantly reduced (p < 0.05 vs placebo) the conjunctival vasopermeability induced by reverse passive Arthus reaction as well as successfully reduced the eosinophil levels in the conjunctival epithelium (p < 0.01 vs placebo) elicited by compound 48/80. Further, Mipragoside successfully reduced the primary signs of ocular inflammation produced by horse serum administration. A radiotracer technique was used to evaluate the disposition of 3H-Mipragoside in the rabbit ocular tissues. Disposition of the drug was monitored at 30, 60, 120 and 240 min. 3H-Mipragoside levels in the inflamed conjunctiva were significantly higher (p < 0.01) than in the control eye.
Record low-threshold index-guided InGaAs/GaAlAsvertical-cavitysurface-emitting laser with a native oxide confinement structure (1995)

An index-guided InGaAs/GaAlAs vertical-cavity surface-emitting laser with a native oxide confinement structure has been proposed and fabricated. A record threshold current of 70 µA was achieved with a 5 µm-diameter core device. The proposed structure provides strong electrical and optical confinements. Also a reduction in nonradiative recombination and an improvement in the thermal resistance can be expected.
Pharmacokinetics of Drugs in Cystic Fibrosis (1990)

Considerable work has been conducted on patients with CF to clearly demonstrate enhanced clearances of many, but not all drugs. The precise mechanisms for enhanced drug clearance in CF remain to be elucidated, and it will be important to examine the two major organs of drug elimination, the kidney and liver, for answers to these questions. Although it has not been studied to date, the role of the lung as a contributor to enhanced drug clearance in CF needs to be considered as well. In the liver it appears that both hepatic biotransformation as well as biliary excretion may be enhanced. In the kidney, there is enhanced CL of acidic drugs, but variable findings for cationic and zwitterionic drugs. The latter finding can be explained on the basis of the pKa of the drugs and the urine pH. It would be most appealing if enhanced renal and nonrenal clearance of drugs in CF could be attributed to a common single defect. At this time, there is no obvious candidate, although altered transmembrane transport would represent a place to start.
Magnetization switching by spin-polarized current in low-resistance magnetic tunnel junction with MgO [001] barrier (2005)

Current-induced magnetization switching (CIMS) was demonstrated in low resistance magnetic tunnel junctions (MTJs) with thin MgO [001] barrier. The resistance change by CIMS was more than 100%, which is much larger than the previous report in Al-O based MTJs. The switching current density was about 2/spl times/10/sup 7/ A/cm/sup 2/, which was comparable with that reported values in metallic multilayers.
Engineering Cytochrome P450 BM3 for Terminal Alkane Hydroxylation (2006)

Abstract Enzymes that catalyze the terminal hydroxylation of alkanes could be used to produce more valuable chemicals from hydrocarbons. Cytochrome P450 BM3 from Bacillus megaterium hydroxylates medium‐chain fatty acids at subterminal positions at high rates. To engineer BM3 for terminal alkane hydroxylation, we performed saturation mutagenesis at selected active‐site residues of a BM3 variant that hydroxylates alkanes. Recombination of beneficial mutations generated a library of BM3 mutants that hydroxylate linear alkanes with a wide range of regioselectivities. Mutant 77‐9H exhibits 52% selectivity for the terminal position of octane. This regioselectivity is octane‐specific and does not transfer to other substrates, including shorter and longer hydrocarbons or fatty acids. These results show that BM3 can be readily molded for regioselective oxidation.
DNA sequence heterogeneity in the three copies of the long 16S–23S rDNA spacer of Enterococcus faecalis isolates (1999)

The possibility of intragenic heterogeneity between copies of the long intergenic (16S-23S rDNA) spacer region (LISR) was investigated by specific amplification of this region from 21 Enterococcus faecalis isolates. Three copies of the LISR (rrnA, B and C) were demonstrated by hybridization of the LISR to genomic DNA cleaved with I-Ceul and SmaI. When the LISR amplicon was digested with Tsp509I, two known nucleotide substitutions were detected, one 4 nt upstream from the 5' end of the tRNA(ala) gene (allele rrnB has the Tsp509I site and rrnA and C do not) and the other 22 nt downstream from the 3' end of the tRNA(ala) gene (rrnC has the Tsp509I site). Sequence differences at these sites were detected at the allelic level (alleles rrnA, B and C) and different combinations of these alleles were designated Tsp Types. Using densitometry to analyse bands from electrophoresis gels, the intra-isolate ratios of the separate alleles (rrnA:rrnB:rrnC) were determined in each Tsp Type: I (0:3:0), II (1:2:0), III (2:0:1), IV (3:0:0), V (2:1:0) and VI (1:1:1). Sequence variation between the three copies of the LISR was confirmed by the detection of at least five other intra-isolate nucleotide substitutions using heteroduplex analysis by conformation-sensitive gel electrophoresis (CSGE) that were not detected by Tsp509I cleavage. Perpendicular denaturing gradient gel electrophoresis was capable of resolving homoduplexes; six to seven out of a possible nine curves were obtained in some isolates. In the isolate where seven curves were obtained one or more further nucleotide substitutions, not detected by Tsp509I cleavage or CSGE, were detected. On the basis of LISR sequence heterogeneity, isolates were categorized into homogeneous (only one allele sequence present) and heterogeneous (two or three allele sequences present). The transition between homogeneous and heterogeneous LISRs may be useful in studying evolutionary mechanisms between E. faecalis isolates.
Quantitation of the interaction of protein kinase C with diacylglycerol and phosphoinositides by time-resolved detection of resonance energy transfer (1993)

Quantitative studies of the binding of protein kinase C (PKC) to lipid cofactors were performed by monitoring resonance energy transfer with time-resolved fluorescence techniques. For that purpose, diacylglycerol (DG), phosphatidylinositol 4,5-biphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidylserine (PS) were labeled with a pyrenyl decanoyl moiety at the sn-2 position of the lipid glycerol. These labeled lipids proved excellent energy acceptors of light-excited tryptophan residues in PKC. The quenching efficiency of the tryptophan fluorescence was determined as function of lipid probe concentration in mixed micelles consisting of poly(oxyethylene)-9-lauryl ether, PS, and various mole fractions of probe lipid. The experimental conditions and method of data analysis allowed the estimation of binding constants of single or multiple pyrene lipids to PKC. The affinity of PKC for inositide lipids increases in the order PI < PIP < PIP2. The affinity of PKC for PIP and PIP2 is higher than that for DG. Determination of PKC activity in the presence of labeled lipids and PS showed that only PIP2 and DG activate PKC. Double-labeling experiments suggest that PIP2 and DG are not able to bind simultaneously to PKC, indicating a reciprocal binding relationship of both cofactors. The results support the notion that, besides DG, PIP2 can be a primary activator of PKC.
Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition (2012)

The use of EpCAM-based enrichment techniques leads to the failure to detect CTC populations that have undergone EMT. Our findings may explain clinical results where low CTC numbers have been reported even in patients with late metastatic cancers. These results are a starting point for the identification of new markers for detection or capture of CTCs, including the mesenchymal-like subpopulations.
The AbrB2 Autorepressor, Expressed from an Atypical Promoter, Represses the Hydrogenase Operon To Regulate Hydrogen Production in Synechocystis Strain PCC6803 (2012)

We have thoroughly investigated the abrB2 gene (sll0822) encoding an AbrB-like regulator in the wild-type strain of the model cyanobacterium Synechocystis strain PCC6803. We report that abrB2 is expressed from an active but atypical promoter that possesses an extended -10 element (TGTAATAT) that compensates for the absence of a -35 box. Strengthening the biological significance of these data, we found that the occurrence of an extended -10 promoter box and the absence of a -35 element are two well-conserved features in abrB2 genes from other cyanobacteria. We also show that AbrB2 is an autorepressor that is dispensable to cell growth under standard laboratory conditions. Furthermore, we demonstrate that AbrB2 also represses the hox operon, which encodes the Ni-Fe hydrogenase of biotechnological interest, and that the hox operon is weakly expressed even though it possesses the two sequences resembling canonical -10 and -35 promoter boxes. In both the AbrB2-repressed promoters of the abrB2 gene and the hox operon, we found a repeated DNA motif [TT-(N(5))-AAC], which could be involved in AbrB2 repression. Supporting this hypothesis, we found that a TT-to-GG mutation of one of these elements increased the activity of the abrB2 promoter. We think that our abrB2-deleted mutant with increased expression of the hox operon and hydrogenase activity, together with the reporter plasmids we constructed to analyze the abrB2 gene and the hox operon, will serve as useful tools to decipher the function and the regulation of hydrogen production in Synechocystis.
Alpha-toxin of Staphylococcus aureus (1991)

Alpha-toxin, the major cytotoxic agent elaborated by Staphylococcus aureus, was the first bacterial exotoxin to be identified as a pore former. The protein is secreted as a single-chain, water-soluble molecule of Mr 33,000. At low concentrations (less than 100 nM), the toxin binds to as yet unidentified, high-affinity acceptor sites that have been detected on a variety of cells including rabbit erythrocytes, human platelets, monocytes and endothelial cells. At high concentrations, the toxin additionally binds via nonspecific absorption to lipid bilayers; it can thus damage both cells lacking significant numbers of the acceptor and protein-free artificial lipid bilayers. Membrane damage occurs in both cases after membrane-bound toxin molecules collide via lateral diffusion to form ring-structured hexamers. The latter insert spontaneously into the lipid bilayer to form discrete transmembrane pores of effective diameter 1 to 2 nm. A hypothetical model is advanced in which the pore is lined by amphiphilic beta-sheets, one surface of which interacts with lipids whereas the other repels apolar membrane constitutents to force open an aqueous passage. The detrimental effects of alpha-toxin are due not only to the death of susceptible targets, but also to the presence of secondary cellular reactions that can be triggered via Ca2+ influx through the pores. Well-studied phenomena include the stimulation of arachidonic acid metabolism, triggering of granule exocytosis, and contractile dysfunction. Such processes cause profound long-range disturbances such as development of pulmonary edema and promotion of blood coagulation.(ABSTRACT TRUNCATED AT 250 WORDS)
IGF-I receptor signalling in transformation and differentiation (2001)

The type 1 insulin-like growth factor receptor (IGF-IR) sends several signals, some of which are contradictory. When the concentrations of insulin receptor substrate 1 (IRS-1), a major substrate of the IGF-IR, are high, the signal is mitogenic, anti-apoptotic, and can even cause malignant transformation. However, in the absence of IRS-1, the IGF-IR sends a differentiation signal, which leads to granulocytic differentiation in haemopoietic cells. The mitogenic signal of the IGF-IR/IRS-1 combination depends largely, but not exclusively, on the activation of the phosphatidylinositol-3 kinase (PI3K).
Streptococcal Histone-Like Protein: Primary Structure of hlpA and Protein Binding to Lipoteichoic Acid and Epithelial Cells (1998)

In addition to its role in the nucleoid, the histone-like protein (HlpA) of Streptococcus pyogenes is believed to act as a fortuitous virulence factor in delayed sequelae by binding to heparan sulfate-proteoglycans in the extracellular matrix of target organs and acting as a nidus for in situ immune complex formation. To further characterize this protein, the hlpA genes were cloned from S. pyogenes, S. gordonii, S. mutans, and S. sobrinus, using PCR amplification, and sequenced. The encoded HlpA protein of S. pyogenes has 91 amino acids, a predicted molecular mass of 9,647 Da, an isoelectric point of 9.81, and 90% to 95% sequence identity with HlpA of several oral streptococci. The consensus sequence of streptococcal HlpA has 69% identity with the consensus sequence of the histone-like HB protein of Bacillus species. Oral viridans group streptococci, growing in chemically defined medium at pH 6.8, released HlpA into the milieu during stationary phase as a result of limited cell lysis. HlpA was not released by these bacteria when grown at pH 6.0 or below. S. pyogenes did not release HlpA during growth in vitro; however, analyses of sera from 155 pharyngitis patients revealed a strong correlation (P < 0.0017) between the production of antibodies to HlpA and antibodies to streptolysin O, indicating that the histone-like protein is released by group A streptococci growing in vivo. Extracellular HlpA formed soluble complexes with lipoteichoic acid in vitro and bound readily to heparan sulfate on HEp-2 cell surfaces. These results support a potential role for HlpA in the pathogenesis of streptococcus-induced tissue inflammation.
The Phenylation of Esters by Reaction with Bromobenzene and Sodium Amide (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Phenylation of Esters by Reaction with Bromobenzene and Sodium AmideWilliam W. Leake and Robert LevineCite this: J. Am. Chem. Soc. 1959, 81, 7, 1627–1630Publication Date (Print):April 1, 1959Publication History Published online1 May 2002Published inissue 1 April 1959https://pubs.acs.org/doi/10.1021/ja01516a029https://doi.org/10.1021/ja01516a029research-articleACS PublicationsRequest reuse permissionsArticle Views594Altmetric-Citations26LEARN 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