gebhart/patrepeval huggingface dataset:
Expression of neutral endopeptidase (enkephalinase) in heterologous COS-1 cells. Characterization of the recombinant enzyme and evidence for a glutamic acid residue at the active site. (1988)

Neutral endopeptidase (EC 3.4.24.11) is an integral membrane protein found in the plasma membrane of many cell types. The cDNA coding for the complete primary structure of neutral endopeptidase has recently been cloned and sequenced (Devault, A. Lazure, C., Nault, C., Le Moual, H., Seidah, N. G., Chretien, M., Kahn, P., Powell, J., Mallet, J., Beaumont, A., Roques, B. P., Crine, P., and Boileau, G. (1987) EMBO J. 6, 1317-1322). Comparison of the sequence of neutral endopeptidase with that of thermolysin, a bacterial Zn-metalloendopeptidase, suggests that Glu-584 in neutral endopeptidase probably corresponds to Glu-143 in thermolysin, which is an essential amino acid involved in catalysis. To test directly the importance of Glu-584 in the catalytic activity of neutral endopeptidase by site-directed metagenesis, we have constructed an expression vector in which the rabbit kidney cDNA encoding the entire neutral endopeptidase sequence is introduced downstream from the SV40 virus early promotor. After transfection in COS-1 monkey kidney cells, this vector was found to promote the expression of a protein with biochemical and catalytic properties identical to kidney neutral endopeptidase. Oligonucleotide-directed mutagenesis of Glu-584 to either valine or aspartic acid completely abolished the enzymatic activity of the recombinant protein without changing its affinity for the substrate-related tritiated inhibitor [3H]N-[(2R,2S)-3-hydroxyamino-carbonyl-2-benzyl-1-oxopropyl]-glycine. This observation clearly identifies Glu-584 as one of the important residues responsible for the catalytic activity of the enzyme.
Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide (1985)

Comparative surface feature analyses of the VP1 sequences of hepatitis A virus (HAV) and poliovirus type 1 allowed an alignment of the two sequences and an identification of probable HAV neutralization antigenic sites. A synthetic peptide containing the HAV-specific amino acid sequence of one of these sites induced anti-HAV-neutralizing antibodies. It is concluded that a structural homology exists between the two viruses, despite minimal primary sequence conservation.
Log-det heuristic for matrix rank minimization with applications to Hankel and Euclidean distance matrices (2004)

We present a heuristic for minimizing the rank of a positive semidefinite matrix over a convex set. We use the logarithm of the determinant as a smooth approximation for rank, and locally minimize this function to obtain a sequence of trace minimization problems. We then present a lemma that relates the rank of any general matrix to that of a corresponding positive semidefinite one. Using this, we readily extend the proposed heuristic to handle general matrices. We examine the vector case as a special case, where the heuristic reduces to an iterative l/sub 1/-norm minimization technique. As practical applications of the rank minimization problem and our heuristic, we consider two examples: minimum-order system realization with time-domain constraints, and finding lowest-dimension embedding of points in a Euclidean space from noisy distance data.
Solubility and Emulsifying Properties of Soy Protein Isolates Modified by Pancreatin (1997)

ABSTRACT Soy protein isolates (SPI) with varying degrees of hydrolysis (DH of 7, 11, 15, 17%) were produced using pancreatin. The surface hydrophobicity indices of pancreatin hydrolyzed SPI (PSPI) (34.5, 34.9, 39. 1, and 40.7 for 7, 11, 15, 17% DH, respectively) were higher than that of SPI (10.5) and control SPI (CSPI) (12.5, 11.9, 12.9, and 12.6 for 10, 60, 120, and 180 min incubation, respectively). The solubilities of PSPI at pH 4.5 were 2.7, 9.1, 11.9, and 18.7%, for 7, 11, 15, and 17% DH, respectively, while the solubilities of SPI and CSPI at the same pH were about 1. 6%. Solubilities of PSPI at pH 7. 0 were &gt; 90% for all DHs tested, while those of SPI and CSPI were 85%. The emulsifying activity index (EAI) of PSPI increased with increasing DH. PSPI with 15% DH had highest EAI (1. 122) which was higher (P &lt; 0. 05) than those of SPI (0.550) and CSPI after 120 min incubation without enzyme (0.568). These results suggest that PSPI could be used as an ingredient for emulsified products and where high solubility at low pH is required.
Gut microbiota diversity predicts immune status in HIV-1 infection (2015)

Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. Our data implicate that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.
Violating Bell's inequality with an artificial atom and a cat state in a cavity (2015)

The `Schrödinger's cat' thought experiment highlights the counterintuitive facet of quantum theory that entanglement can exist between microscopic and macroscopic systems, producing a superposition of distinguishable states like the fictitious cat that is both alive and dead. The hallmark of entanglement is the detection of strong correlations between systems, for example by the violation of Bell's inequality. Using the CHSH variant of the Bell test, this violation has been observed with photons, atoms, solid state spins, and artificial atoms in superconducting circuits. For larger, more distinguishable states, the conflict between quantum predictions and our classical expectations is typically resolved due to the rapid onset of decoherence. To investigate this reconciliation, one can employ a superposition of coherent states in an oscillator, known as a cat state. In contrast to discrete systems, one can continuously vary the size of the prepared cat state and therefore its dependence on decoherence. Here we demonstrate and quantify entanglement between an artificial atom and a cat state in a cavity, which we call a `Bell-cat' state. We use a circuit QED architecture, high-fidelity measurements, and real-time feedback control to violate Bell's inequality without post-selection or corrections for measurement inefficiencies. Furthermore, we investigate the influence of decoherence by continuously varying the size of created Bell-cat states and characterize the entangled system by joint Wigner tomography. These techniques provide a toolset for quantum information processing with entangled qubits and resonators. While recent results have demonstrated a high level of control of such systems, this experiment demonstrates that information can be extracted efficiently and with high fidelity, a crucial requirement for quantum computing with resonators.
The probioticEscherichia colistrain Nissle 1917 interferes with invasion of human intestinal epithelial cells by different enteroinvasive bacterial pathogens (2004)

The probiotic Escherichia coli strain Nissle 1917 (Mutaflor) of serotype O6:K5:H1 was reported to protect gnotobiotic piglets from infection with Salmonella enterica serovar Typhimurium. An important virulence property of Salmonella is invasion of host epithelial cells. Therefore, we tested for interference of E. coli strain Nissle 1917 with Salmonella invasion of INT407 cells. Simultaneous administration of E. coli strain Nissle 1917 and Salmonella resulted in up to 70% reduction of Salmonella invasion efficiency. Furthermore, invasion of Yersinia enterocolitica, Shigella flexneri, Legionella pneumophila and even of Listeria monocytogenes were inhibited by the probiotic E. coli strain Nissle 1917 without affecting the viability of the invasive bacteria. The observed inhibition of invasion was not due to the production of microcins by the Nissle 1917 strain because its isogenic microcin-negative mutant SK22D was as effective as the parent strain. Reduced invasion rates were also achieved if strain Nissle 1917 was separated from the invasive bacteria as well as from the INT407 monolayer by a membrane non-permeable for bacteria. We conclude E. coli Nissle 1917 to interfere with bacterial invasion of INT407 cells via a secreted component and not relying on direct physical contact with either the invasive bacteria or the epithelial cells.
Disease-Free Survival Versus Overall Survival As a Primary End Point for Adjuvant Colon Cancer Studies: Individual Patient Data From 20,898 Patients on 18 Randomized Trials (2005)

In patients treated on phase III adjuvant colon clinical trials, DFS and OS are highly correlated, both within patients and across trials. These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens, although marginally significant DFS improvements may not translate into significant OS benefits.
Nanoscale Transformations in Metastable, Amorphous, Silicon‐Rich Silica (2016)

Electrically biasing thin films of amorphous, substoichiometric silicon oxide drives surprisingly large structural changes, apparent as density variations, oxygen movement, and ultimately, emission of superoxide ions. Results from this fundamental study are directly relevant to materials that are increasingly used in a range of technologies, and demonstrate a surprising level of field-driven local reordering of a random oxide network.
Structural characterization of glycopeptide antibiotics related to vancomycin by fast atom bombardment mass spectrometry. (1985)

A series of glycopeptide antibiotics related to the vancomycin-ristocetin family have been successfully analyzed by fast atom bombardment mass spectrometry (FABMS). The FAB mass spectra of glycopeptides weighing up to 2,100 daltons exhibit intense molecular ions and fragment ions from which information concerning carbohydrate composition and sequence are readily obtained. Careful adjustment of the FABMS experimental conditions has enabled the accurate masses of the glycopeptides to be determined by high resolution FABMS with an accuracy of better than six ppm. Comparison of the observed molecular ion cluster pattern with calculated isotope distributions reveals the precise number of chlorine atoms in these molecules, which, together with the accurate mass data, can be used to restrict the number of possible elemental compositions to a meaningfully small value. These techniques have been used to characterize several glycopeptides of known structure including ristocetin, actinoidin, avoparcin, vancomycin and A35512B, as well as aridicins A, B and C which are three new, novel members of the vancomycin class.
Subgap states in transparent amorphous oxide semiconductor, In–Ga–Zn–O, observed by bulk sensitive x-ray photoelectron spectroscopy (2008)

We investigated the electronic states in amorphous In–Ga–Zn–O films with high carrier concentrations by optical absorption and hard x-ray photoelectron spectroscopy (HX-PES). Films having different Hall mobilities were prepared and their annealing effects were examined. All HX-PES spectra showed Fermi edge structures and extra subgap densities of states (DOSs). Tail-like structures observed in the optical spectra originate from subgap DOSs (⪢1020cm−3) near valence band maximas (VBMs). Subgap DOSs near VBMs provide a reason why In–Ga–Zn–O thin film transistors show hard saturation in off states and are difficult to operate in an inversion p-channel mode.
Elliptic grid generation with orthogonality and spacing control on an arbitrary number of boundaries (1990)

A procedure for the generation of two and quasi-three-dimensional grids with control of orthogonality and spacing with respect to any and/or all boundaries of the domain is described. The elliptic grid generation equations of Thompson are solved implicitly. Control of the grid behavior is achieved through the introduction of forcing functions terms in the manner of Steger and Sorenson or in a modification of the method of Hilgenstock. The forcing function terms are constructed on the boundaries and propagated into the domain using transfinite Lagrangian bivariate interpolation. An anisotropic transfinite stencil is introduced and is shown to produce excellent grid behavior particularly in the vicinity of corner singularities. Emphasis is placed on the generation of viscous grids and the method is shown to be suited for use in the generation of grids for internal as well as external flow geometries. A FORTRAN program named PISCES has been written to implement the algorithm. Examples of grids for internal and external flows are given that highlight the characteristics and behavior of the algorithm.
A protocol for generating high numbers of mature and functional human mast cells from peripheral blood (2007)

This study describes an efficient protocol for generating mature MCs from human peripheral blood with a functional phenotype of connective tissue-type MCs. Use of these cultured human MCs will increase our knowledge and understanding about human MC development and biology in human disease.
The stress-activated protein kinases are major c-Jun amino-terminal kinases activated by ischemia and reperfusion (1994)

The signal transduction pathways that mediate activation of trans acting factors controlling an organ's response to ischemia are unknown. The stress-activated protein kinases (SAPKs), a subfamily of the extracellular signal-regulated kinases (ERKs), phosphorylate c-Jun within the amino-terminal transactivation domain and are activated in response to a variety of cellular stresses. We determined whether SAPKs are activated in response to ischemia, an extreme, albeit common, pathophysiologic stress. Rats underwent 40 min of renal ischemia followed by reperfusion for 0, 5, 20, or 90 min. SAPKs were immunoprecipitated from kidney lysates and kinase activity assayed with recombinant GST-c-Jun(1-135), containing the amino-terminal transactivation domain of c-Jun as substrate. SAPKs were not activated by ischemia alone, but reperfusion for as little as 5 min was associated with a 4.6-fold increase in kinase activity. Kinase activity was increased 7.6-fold at 20 min following reperfusion and remained elevated at 90 min of reperfusion (4.9-fold). In contrast, activity of the related ERK-1 and -2 was increased only 1.3-fold and only at the 5-min reperfusion time point. When SAPKs were immunodepleted from kidney extracts prior to incubation of the extracts with agarose-coupled GST-c-Jun(1-135), it was found that SAPKs accounted for the majority of the amino-terminal c-Jun kinase activity of kidney at 5 min following reperfusion. In Madin-Darby canine kidney epithelial cells, ATP repletion, following ATP depletion induced by chemical anoxia, was associated with a 9-15-fold activation of SAPKs with a similar time course of activation to that seen in the kidney after ischemia and reperfusion. In conclusion, the SAPKs are markedly activated very early after reperfusion of ischemic kidney and following ATP repletion of anoxic cells in culture. We propose that this activation of SAPKs may trigger part of the kidney's early genetic response to ischemia, possibly by enhancing trans acting activity of c-Jun.
Production of l-phenylalanine from glycerol by a recombinant Escherichia coli (2009)

The production of L-phenylalanine is conventionally carried out by fermentations that use glucose or sucrose as the carbon source. This work reports on the use of glycerol as an inexpensive and abundant sole carbon source for producing L-phenylalanine using the genetically modified bacterium Escherichia coli BL21(DE3). Fermentations were carried out at 37 degrees C, pH 7.4, using a defined medium in a stirred tank bioreactor at various intensities of impeller agitation speeds (300-500 rpm corresponding to 0.97-1.62 m s(-1) impeller tip speed) and aeration rates (2-8 L min(-1), or 1-4 vvm). This highly aerobic fermentation required a good supply of oxygen, but intense agitation (impeller tip speed approximately 1.62 m s(-1)) reduced the biomass and L-phenylalanine productivity, possibly because of shear sensitivity of the recombinant bacterium. Production of L-phenylalanine was apparently strongly associated with growth. Under the best operating conditions (1.30 m s(-1) impeller tip speed, 4 vvm aeration rate), the yield of L-phenylalanine on glycerol was 0.58 g g(-1), or more than twice the best yield attainable on sucrose (0.25 g g(-1)). In the best case, the peak concentration of L-phenylalanine was 5.6 g L(-1), or comparable to values attained in batch fermentations that use glucose or sucrose. The use of glycerol for the commercial production of L-phenylalanine with E. coli BL21(DE3) has the potential to substantially reduce the cost of production compared to sucrose- and glucose-based fermentations.
Drug−Protein Adducts:  An Industry Perspective on Minimizing the Potential for Drug Bioactivation in Drug Discovery and Development (2003)

It is generally accepted that there is neither a well-defined nor a consistent link between the formation of drug−protein adducts and organ toxicity. Because the potential does exist, however, for these processes to be causally related, the general strategy at Merck Research Laboratories has been to minimize reactive metabolite formation to the extent possible by appropriate structural modification during the lead optimization stage. This requires a flexible approach to defining bioactivation issues in a variety of metabolism vectors and typically involves the initial use of small molecule trapping agents to define the potential for bioactivation. At some point, however, there is a requirement to synthesize a radiolabeled tracer and to undertake covalent binding studies in vitro, usually in liver microsomal (and sometimes hepatocyte) preparations from preclinical species and human, and also in vivo, typically in the rat. This paper serves to provide one pragmatic approach to addressing the issue of bioactivation from an industry viewpoint based on protocols adopted by Merck Research Laboratories. The availability of a dedicated Labeled Compound Synthesis group, coupled to a close working relationship between Drug Metabolism and Medicinal Chemistry, represents a framework within which this perspective becomes viable; the overall aim is to bring safer drugs to patients.
FGF-8 isoforms differ in NIH3T3 cell transforming potential. (1995)

We previously identified Fgf-8 as a frequently activated gene in tumors from mouse mammary tumor virus-infected Wnt-1 transgenic mice, suggesting that Fgf-8 is a proto-oncogene. We further determined that multiple, secreted protein isoforms that differ at their mature amino termini are encoded by alternatively spliced mRNAs transcribed from the gene. We now present evidence that there are differences in the potency of NIH3T3 cell transformation displayed by three of the FGF (fibroblast growth factor)-8 isoforms. We find that stable transfection of a cDNA for the FGF-8b isoform leads to marked morphological transformation of NIH3T3 cells and rapid tumorigenicity of the transfected cells in nude mice. In contrast, transfection of a cDNA for the FGF-8a or FGF-8c isoform results in moderate morphological changes in the NIH3T3 cells, and the transfected cells are weakly tumorigenic in nude mice. All three transfections result in cells that express comparable amounts of Fgf-8 mRNA and that produce the FGF-8 protein isoforms. The morphological changes observed in NIH3T3 cells can be reproduced by the addition of recombinant FGF-8 protein isoforms to the culture medium. Therefore, these results indicate that there are differences in the potency of transformation of NIH3T3 cells by FGF-8 protein isoforms and suggest that these FGF-8 isoforms may have different in vivo functions.
Adjuvant synergy: The effects of nasal coadministration of adjuvants (2004)

Modern peptide and protein subunit vaccines suffer from poor immunogenicity and require the use of adjuvants. However, none of the currently licensed adjuvants can elicit cell-mediated immunity or are suitable for mucosal immunization. In this study we explored the immunological effect of nasal co-administration of adjuvants with distinct functions: cholera toxin subunit B, a potent mucosal adjuvant that induces strong humoral responses, muramy di-peptide (MDP), an adjuvant known to elicit cell mediated immunity but rarely used nasally, and chitosan, an adjuvant that achieves specific physiological effects on mucosal membranes that improve antigen uptake. Groups of five female BALB/c mice received on days 1 and 56 nasal instillations of the recombinant Helicobacter pylori antigen urease admixed to single or multiple adjuvant combinations. Serum IgG kinetics were followed over 24 weeks. At the conclusion of the experiment, local antibody responses were determined and antigen-specific recall responses in splenocyte cultures were assayed for proliferation and cytokine production. The combination of adjuvants was shown to further contribute to the increased antigenicity of recombinant H. pylori urease. The data presented here outline and support facilitation of increased immunomodulation by an adjuvant previously defined as an effective mucosal adjuvant (chitosan) for another adjuvant (MDP) that is not normally effective via this route.
Does a Fibronectin and Aggrecan Complex Play a Role in Painful Vertebral Disks? (2013)

The FAC was identified in some painful disks by diskography. There was no significant correlation between the Pfirrmann grade or pre/intraoperative pain scores during diskography and complex concentrations within the disk measured by disk lavage.
The highly conserved amino acid sequence motif Tyr-Gly-Asp-Thr-Asp-Ser in alpha-like DNA polymerases is required by phage phi 29 DNA polymerase for protein-primed initiation and polymerization. (1990)

The alpha-like DNA polymerases from bacteriophage phi 29 and other viruses, prokaryotes and eukaryotes contain an amino acid consensus sequence that has been proposed to form part of the dNTP binding site. We have used site-directed mutants to study five of the six highly conserved consecutive amino acids corresponding to the most conserved C-terminal segment (Tyr-Gly-Asp-Thr-Asp-Ser). Our results indicate that in phi 29 DNA polymerase this consensus sequence, although irrelevant for the 3'----5' exonuclease activity, is essential for initiation and elongation. Based on these results and on its homology with known or putative metal-binding amino acid sequences, we propose that in phi 29 DNA polymerase the Tyr-Gly-Asp-Thr-Asp-Ser consensus motif is part of the dNTP binding site, involved in the synthetic activities of the polymerase (i.e., initiation and polymerization), and that it is involved particularly in the metal binding associated with the dNTP site.
Differential Expression of Proteoglycan Epitopes and Growth Characteristics of Intervertebral Disc Cells Grown in Alginate Bead Culture (2001)

This study assessed the growth characteristics and proteoglycan (PG) production in vitro of cells isolated from various zones; annulus fibrosus (AF), the transitional zone (TZ, an opalescent region situated between the AF and nucleus pulposus, NP) and the NP of the ovine intervertebral disc. The isolated cells were subsequently cultured in calcium alginate microspheres. Cellular metabolic activity was assessed over the 10 days of culture by the bioreduction of a tetrazolium dye substrate to a coloured formazan chromophore which could be measured colorimetrically at 490 nm. These data were correlated with the DNA content of beads measured using the fluorescent dye Hoechst 33258. Viable and non-viable cells in alginate beads were also assessed histochemically using the fluorescent dyes 5-chloromethylfluorescein diacetate and ethidium homodimer-1. PGs synthesised in culture were examined immunohistologically using monoclonal antibodies to defined glycosaminoglycan side chain PG epitopes. The results obtained clearly showed that AF and TZ cells differed from NP cells in the measured indices of cellular metabolism and in the extent of matrix deposition. In contrast to cells from the NP the cells from the AF and TZ were more metabolically active and programmed more to cellular proliferation than to matrix production.