gebhart/patrepeval huggingface dataset:
The Cytotoxic Effect of Mouse Macrophages Stimulated in Vitro by a β‐1,3‐d‐Glucan from Yeast Cell Walls (1982)

Macrophages stimulated by an insoluble beta-1,3-D-glucan from yeast cell walls were able to destroy tumour cells as measured by the release of radioactive label from prelabelled 14C-thymidine cells. Target cells were B-16 melanoma, P-815 mastocytoma, and the L-929 cell line. A significant target cell killing by macrophages stimulated by glucan was observed after 72-96 h. The cytolysis of L-929 cells was investigated in some detail. No stable soluble cytolytic factor appeared to be released into the medium during the stimulation of macrophages by glucan, since cell-free spent medium had no cytotoxic effect on L-929 cells. The densities of the macrophage monolayers were critical for an effective target cell killing; dense cultures showed more cytotoxicity than less dense cultures. The kinetics of the development of macrophage-mediated cytotoxicity suggests a minimum stimulation period of 4 days for maximal cytolysis.
High-Resolution Labeling and Functional Manipulation of Specific Neuron Types in Mouse Brain by Cre-Activated Viral Gene Expression (2008)

We describe a method that combines Cre-recombinase knockin mice and viral-mediated gene transfer to genetically label and functionally manipulate specific neuron types in the mouse brain. We engineered adeno-associated viruses (AAVs) that express GFP, dsRedExpress, or channelrhodopsin (ChR2) upon Cre/loxP recombination-mediated removal of a transcription-translation STOP cassette. Fluorescent labeling was sufficient to visualize neuronal structures with synaptic resolution in vivo, and ChR2 expression allowed light activation of neuronal spiking. The structural dynamics of a specific class of neocortical neuron, the parvalbumin-containing (Pv) fast-spiking GABAergic interneuron, was monitored over the course of a week. We found that although the majority of Pv axonal boutons were stable in young adults, bouton additions and subtractions on axonal shafts were readily observed at a rate of 10.10% and 9.47%, respectively, over 7 days. Our results indicate that Pv inhibitory circuits maintain the potential for structural re-wiring in post-adolescent cortex. With the generation of an increasing number of Cre knockin mice and because viral transfection can be delivered to defined brain regions at defined developmental stages, this strategy represents a general method to systematically visualize the structure and manipulate the function of different cell types in the mouse brain.
Identification of Genotypic Changes in Human Immunodeficiency Virus Protease That Correlate with Reduced Susceptibility to the Protease Inhibitor Lopinavir among Viral Isolates from Protease Inhibitor-Experienced Patients (2001)

The association of genotypic changes in human immunodeficiency virus (HIV) protease with reduced in vitro susceptibility to the new protease inhibitor lopinavir (previously ABT-378) was explored using a panel of viral isolates from subjects failing therapy with other protease inhibitors. Two statistical tests showed that specific mutations at 11 amino acid positions in protease (L10F/I/R/V, K20M/R, L24I, M46I/L, F53L, I54L/T/V, L63P, A71I/L/T/V, V82A/F/T, I84V, and L90M) were associated with reduced susceptibility. Mutations at positions 82, 54, 10, 63, 71, and 84 were most closely associated with relatively modest (4- and 10-fold) changes in phenotype, while the K20M/R and F53L mutations, in conjunction with multiple other mutations, were associated with >20- and >40-fold-reduced susceptibility, respectively. The median 50% inhibitory concentrations (IC(50)) of lopinavir against isolates with 0 to 3, 4 or 5, 6 or 7, and 8 to 10 of the above 11 mutations were 0.8-, 2.7-, 13.5-, and 44.0-fold higher, respectively, than the IC(50) against wild-type HIV. On average, the IC(50) of lopinavir increased by 1.74-fold per mutation in isolates containing three or more mutations. Each of the 16 viruses that displayed a >20-fold change in susceptibility contained mutations at residues 10, 54, 63, and 82 and/or 84, along with a median of three mutations at residues 20, 24, 46, 53, 71, and 90. The number of protease mutations from the 11 identified in these analyses (the lopinavir mutation score) may be useful for the interpretation of HIV genotypic resistance testing with respect to lopinavir-ritonavir (Kaletra) regimens and may provide insight into the genetic barrier to resistance to lopinavir-ritonavir in both antiretroviral therapy-naive and protease inhibitor-experienced patients.
Customized brackets and the straight arch technique combined in one appliance to simplify lingual orthodontics (2012)

The concept of the appliance we describe in this article is based on a number of technological advances. The brackets, created in accordance with CAD/CAM are the product of an original process that makes them resistant to de-bonding providing a high resistance to bracket loss. They are also compatible with the use of a veritable straight wire enabling the use of prefabricated standard wires. The manufacturing process uses a maximum of digitized resources to elaborate a numerical set-up usable by the practitioners. A 3D computerised treatment control is performed from the beginning to the end of the assembly line and warrants a perfect precision of the bonding placement.Appliances are completely personalized for each patient taking into account particular anatomic features as well as the prescriptions of practitioners. As a result practitioners will benefit from a number of theoretical advantages making treatment more pleasant and functionally smoother at every phase of therapy. Managing the Lingualjet appliance is simple and transforms straight wire lingual therapy into a procedure comparable in every way to traditional use of the straight wire in buccally bonded attachments.
The Probability of Unique Solutions of Sequencing by Hybridization (1994)

We determine the asymptotic limiting probability as m → ∞ that a random string of length m over some alphabet ∑ can be determined uniquely by its substrings of length l. This is an abstraction of a problem faced when trying to sequence DNA clones by SBH.
Supramolecular Azobenzene-Based Materials for Optical Generation of Microstructures (2007)

We propose a concept of supramolecular materials for effective all-optical generation of surface relief structures and optical anisotropy. The materials are based on the ionic interactions between photochromic azobenzene units and polyelectrolytes. The materials are easy to produce and they allow the inscription of the 1.8 μm deep surface relief gratings. Moreover, the induced structures were thermally very stable. Both distinctive features of the new materials, namely, the dynamic behavior of molecular orientation and the high thermal stability of surface structures, have been explained in terms of the network of oppositely charged ions inherent to the materials. Due to the simplicity and versatility of the concept, the new family of materials for different applications in optics, sensorics, and biology may be designed.
Immunogenomic engineering of a plug-and-(dis)play hybridoma platform (2016)

Hybridomas, fusions of primary mouse B cells and myelomas, are stable, rapidly-proliferating cell lines widely utilized for antibody screening and production. Antibody specificity of a hybridoma clone is determined by the immunoglobulin sequence of the primary B cell. Here we report a platform for rapid reprogramming of hybridoma antibody specificity by immunogenomic engineering. Here we use CRISPR-Cas9 to generate double-stranded breaks in immunoglobulin loci, enabling deletion of the native variable light chain and replacement of the endogenous variable heavy chain with a fluorescent reporter protein (mRuby). New antibody genes are introduced by Cas9-targeting of mRuby for replacement with a donor construct encoding a light chain and a variable heavy chain, resulting in full-length antibody expression. Since hybridomas surface express and secrete antibodies, reprogrammed cells are isolated using flow cytometry and cell culture supernatant is used for antibody production. Plug-and-(dis)play hybridomas can be reprogrammed with only a single transfection and screening step.
Human nuclear clusterin mediates apoptosis by interacting with Bcl‐XL through C‐terminal coiled coil domain (2011)

Clusterin (CLU), a glycoprotein, is involved in apoptosis, producing two alternatively spliced isoforms in various cell types. The pro-apoptotic CLU appears to be a nuclear isoform (nuclear clusterin; nCLU), and the secretory CLU (sCLU) is thought to be anti-apoptotic. The detailed molecular mechanism of nCLU as a pro-apoptotic molecule has not yet been clear. In the current study, overexpressed nCLU induced apoptosis in human kidney cells. Biochemical studies revealed that nCLU sequestered Bcl-XL via a putative BH3 motif in the C-terminal coiled coil (CC2) domain, releasing Bax, and promoted apoptosis accompanied by activation of caspase-3 and cytochrome c release. These results suggest a novel mechanism of apoptosis mediated by nCLU as a pro-apoptotic molecule.
Shade trees (1984)

Shading is an important part of computer imagery, but shaders have been based on fixed models to which all surfaces must conform. As computer imagery becomes more sophisticated, surfaces have more complex shading characteristics and thus require a less rigid shading model. This paper presents a flexible tree-structured shading model that can represent a wide range of shading characteristics. The model provides an easy means for specifying complex shading characteristics. It is also efficient because it can tailor the shading calculations to each type of surface.
On the Antimicrobial and Hemolytic Activities of Amphiphilic β ‐Peptides (2001)

Not generally harmful: The antimicrobial and hemolytic activity of amphiphilic β-homo (β-H) peptides with the general formula H-(β-HAla-β-HLys-β-HPhe)-OH (see schematic representation) were investigated to unravel their potential for applications in medicinal chemistry. Only moderate activities were found for some of the peptides tested, critically depending on the side-chain composition of the amphiphilic helix.
Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent (2004)

These results suggest that a subset of immediate early and SRF target genes are activated by the Rho-MKL pathway. MKL may also contribute to the induction of other SRF target genes however its role is not essential, possibly due to other activation mechanisms such as MAPK phosphorylation of TCFs.
Overproduction of Threonine Aldolase Circumvents the Biosynthetic Role of Pyruvate Decarboxylase in Glucose-Limited Chemostat Cultures ofSaccharomyces cerevisiae (2003)

Pyruvate decarboxylase-negative (Pdc(-)) mutants of Saccharomyces cerevisiae require small amounts of ethanol or acetate to sustain aerobic, glucose-limited growth. This nutritional requirement has been proposed to originate from (i) a need for cytosolic acetyl coenzyme A (acetyl-CoA) for lipid and lysine biosynthesis and (ii) an inability to export mitochondrial acetyl-CoA to the cytosol. To test this hypothesis and to eliminate the C(2) requirement of Pdc(-) S. cerevisiae, we attempted to introduce an alternative pathway for the synthesis of cytosolic acetyl-CoA. The addition of L-carnitine to growth media did not restore growth of a Pdc(-) strain on glucose, indicating that the C(2) requirement was not solely due to the inability of S. cerevisiae to synthesize this compound. The S. cerevisiae GLY1 gene encodes threonine aldolase (EC 4.1.2.5), which catalyzes the cleavage of threonine to glycine and acetaldehyde. Overexpression of GLY1 enabled a Pdc(-) strain to grow under conditions of carbon limitation in chemostat cultures on glucose as the sole carbon source, indicating that acetaldehyde formed by threonine aldolase served as a precursor for the synthesis of cytosolic acetyl-CoA. Fractionation studies revealed a cytosolic localization of threonine aldolase. The absence of glycine in these cultures indicates that all glycine produced by threonine aldolase was either dissimilated or assimilated. These results confirm the involvement of pyruvate decarboxylase in cytosolic acetyl-CoA synthesis. The Pdc(-) GLY1 overexpressing strain was still glucose sensitive with respect to growth in batch cultivations. Like any other Pdc(-) strain, it failed to grow on excess glucose in batch cultures and excreted pyruvate when transferred from glucose limitation to glucose excess.
Relative Spatial Positions of Tryptophan and Cationic Residues in Helical Membrane-active Peptides Determine Their Cytotoxicity (2011)

The cytotoxic activity of 10 analogs of the idealized amphipathic helical 21-mer peptide (KAAKKAA)3, where three of the Ala residues at different positions have been replaced with Trp residues, has been investigated. The peptide's cytotoxic activity was found to be markedly dependent upon the position of the Trp residues within the hydrophobic sector of an idealized α-helix. The peptides with Trp residues located opposite the cationic sector displayed no antitumor activity, whereas those peptides with two or three Trp residues located adjacent to the cationic sector exhibited high cytotoxic activity when tested against three different cancer cell lines. Dye release experiments revealed that in contrast to the peptides with Trp residues located opposite the cationic sector, the peptides with Trp residues located adjacent to the cationic sector induced a strong permeabilizing activity from liposomes composed of a mixture of zwitterionic phosphatidylcholine and negatively charged phosphatidylserine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS)) (2:1) but not from liposomes composed of zwitterionic phosphatidylcholine, POPC. Fluorescence blue shift and quenching experiments revealed that Trp residues inserted deeper into the hydrophobic environment of POPC/POPS liposomes for peptides with high cytotoxic activity. Through circular dichroism studies, a correlation between the cytotoxic activity and the α-helical propensity was established. Structural studies of one inactive and two active peptides in the presence of micelles using NMR spectroscopy showed that only the active peptides adopted highly coiled to helical structures when bound to a membrane surface.
Antioxidative and antihemolytic activities of soybean isoflavones (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntioxidative and antihemolytic activities of soybean isoflavonesMichael Naim, Benjamin Gestetner, Aron Bondi, and Yehudith BirkCite this: J. Agric. Food Chem. 1976, 24, 6, 1174–1177Publication Date (Print):November 1, 1976Publication History Published online1 May 2002Published inissue 1 November 1976https://pubs.acs.org/doi/10.1021/jf60208a029https://doi.org/10.1021/jf60208a029research-articleACS PublicationsRequest reuse permissionsArticle Views467Altmetric-Citations171LEARN 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
Synthesis and Characterization of Bradykinin B2 Receptor Agonists Containing Constrained Dipeptide Mimics (1999)

We have previously shown that substitution of the D-Tic-Oic dipeptide by a (3S)-[amino]-5-(carbonylmethyl)-2,3-dihydro-1, 5-benzothiazepin-4(5H)-one (D-BT) moiety in the bradykinin B(2) receptor antagonist HOE 140 resulted in a full potent and selective bradykinin B(2) receptor agonist (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-Arg-OH, JMV1116) exhibiting a high affinity for the human receptor (K(i) 0.7 nM). In the present study, we have investigated the effects of replacement of the D-Tic-Oic moiety by various constrained dipeptide mimetics. The resulting compounds were tested for their binding affinity toward the cloned human B(2) receptor and for their functional interaction with the bradykinin-induced contraction of isolated human umbilical vein. Subsequently, we have designed novel bradykinin B(2) receptor agonists which are likely to be resistant to enzymatic cleavage by endopeptidases and which might represent interesting new pharmacological tools. In an attempt to increase the potency of compound JMV1116, both its N-terminal part and the D-BT moiety were modified. Substitution of the D-arginine residue by a L-lysine residue led to a 10-fold more potent bradykinin B(2) ligand [compound 22 (JMV1465) (K(i) 0.07 nM)], retaining full agonist activity on human umbilical vein. Substitution of the D-BT moiety by a (3S)-[amino]-5-(carbonylmethyl)-2,3-dihydro-8-methyl-1, 5-benzothiazepin-4(5H)-one [D-BT(Me)] moiety led to compound 23 (JMV1609) which exhibited a higher agonist activity (pD(2) = 7.4) than JMV1116 (pD(2) = 6.8).
A Demonstration of TouchLight, an Imaging Touch Screen and Display for Gesture-Based Interaction (2004)

A novel touch screen technology is presented. TouchLight uses simple image processing techniques to combine the output of two video cameras placed behind a semi-transparent plane in front of the user. The resulting image shows objects that are on the plane. This technique is well suited for application with a commercially available projection screen material (DNP HoloScreen) which permits projection onto a transparent sheet of acrylic plastic in normal indoor lighting conditions. The resulting touch screen display system transforms an otherwise normal sheet of acrylic plastic into a high bandwidth input/output surface suitable for gesture-based interaction.
Growth‐Inhibiting Activities of Phenethyl Isothiocyanate and Its Derivatives against Intestinal Bacteria (2009)

The growth-inhibiting activities of Sinapis alba L. seed-derived materials were examined on the growth of Bifidobacterium bifidum, B. breve, B. longum, Clostridium difficile, C. perfringens, Escherichia coli, Lactobacillus acidophilus, and L. casei. The active component of S. alba seeds was purified using silica gel column chromatography and HPLC and was identified as phenethyl isothiocyanate by various spectroscopic analyses. The antimicrobial activity of phenethyl isothiocyanate varied according to the dose and bacterial strain tested. Phenethyl isothiocyanate strongly inhibited the growth of C. difficile and C. perfringens at 1 mg/disc, and weakly (+) inhibited its growth at 0.1 mg/disc. Furthermore, phenethyl isothiocyanate moderately (++) inhibited the growth of E. coli at a dose of 2 mg/disc, but did not inhibit the growth of bifidobacteria and lactobacilli. Addition of various functional groups to isothiocyanates resulted in selective inhibitory activity against harmful bacteria with low concentrations of aromatic isothiocyanates demonstrating greater inhibitory activity against clostridia and E. coli than aliphatic isothiocyanates. In conclusion, aromatic isothiocyanates containing phenethyl-, benzyl-, and benzoyl-groups might be useful in the development of novel preventive and therapeutic agents against diseases caused by harmful intestinal bacteria.
Bioreactor Operations—Preparation, Sterilization, Charging, Culture Initiation and Harvesting (2000)

Preparation




Cleaning




Instrumentation




Maintenance of Valves and Changing of O-Rings and Gaskets




Connections to Receive Charging Fluids






Sterilization




Theory




Principles (Unambiguous Flow of Steam)




Monitoring and Control






Charging




Fluid Transfers




Volume Control (Weight, Level)




Foam/Tangential Inlets




Sterile Connections/Disconnections




pH Priming




Instrumentation Checks






Culture Initiation




Transfer of Cell Inoculum




Initial Mixing/Planting Conditions




Initial Sampling




Control Cultures Set Up






Harvesting




Discharge






Nomenclature (See Frontmatter page xvii)




Bibliography





Keywords:

good manufacturing practice;
cell lines;
cell types;
cell culture media
Heat Shock Proteins 70 and 90 Inhibit Early Stages of Amyloid β-(1–42) Aggregation in Vitro (2006)

Alzheimer disease is a neurological disorder that is characterized by the presence of fibrils and oligomers composed of the amyloid beta (Abeta) peptide. In models of Alzheimer disease, overexpression of molecular chaperones, specifically heat shock protein 70 (Hsp70), suppresses phenotypes related to Abeta aggregation. These observations led to the hypothesis that chaperones might interact with Abeta and block self-association. However, although biochemical evidence to support this model has been collected in other neurodegenerative systems, the interaction between chaperones and Abeta has not been similarly explored. Here, we examine the effects of Hsp70/40 and Hsp90 on Abeta aggregation in vitro. We found that recombinant Hsp70/40 and Hsp90 block Abeta self-assembly and that these chaperones are effective at substoichiometric concentrations (approximately 1:50). The anti-aggregation activity of Hsp70 can be inhibited by a nonhydrolyzable nucleotide analog and encouraged by pharmacological stimulation of its ATPase activity. Finally, we were interested in discerning what type of amyloid structures can be acted upon by these chaperones. To address this question, we added Hsp70/40 and Hsp90 to pre-formed oligomers and fibrils. Based on thioflavin T reactivity, the combination of Hsp70/40 and Hsp90 caused structural changes in oligomers but had little effect on fibrils. These results suggest that if these chaperones are present in the same cellular compartment in which Abeta is produced, Hsp70/40 and Hsp90 may suppress the early stages of self-assembly. Thus, these results are consistent with a model in which pharmacological activation of chaperones might have a favorable therapeutic effect on Alzheimer disease.
hDAF porcine cardiac xenograft maintains cardiac output after orthotopic transplantation into baboon – a perioperative study (2005)

Our results demonstrate that in the early phase after orthotopic transplantation of hDAF pig hearts to baboons, cardiac function of the donor heart is maintained and exceeds baseline CO. However, in the early intraoperative phase this was only possible by using inotropic substances and vasopressors due to the inevitable blood loss and dilution by the priming of the bypass circuit.