gebhart/patrepeval huggingface dataset:
Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions. (1991)

B19 parvovirus is pathogenic in humans, causing fifth disease, transient aplastic crisis, some cases of hydrops fetalis, and acquired pure red cell aplasia. Efforts to develop serologic assays and vaccine development have been hampered by the virus's extreme tropism for human bone marrow and the absence of a convenient culture system. We constructed recombinants containing either the major (VP2) or minor (VP1) structural proteins of B19 in a baculovirus-based plasmid, from which the polyhedrin gene had been deleted; these recombinant plasmids were used to generate recombinant infectious baculovirus. Subsequent infection of insect cells in vitro resulted in high-level expression of either B19VP1 or VP2. Parvovirus capsids were obtained by self-assembly in cell cultures coinfected with either VP1- and VP2-containing baculoviruses or, surprisingly, VP2-containing baculoviruses alone. Empty B19 capsids composed of VP1 and VP2 could replace serum virus as a source of antigen in a conventional immunoassay for detection of either IgG or IgM antiparvovirus antibodies in human serum. Immunization of rabbits with capsids composed of VP1 and VP2 resulted in production of antisera that recognized serum parvovirus on immunoblot and neutralized parvovirus infectivity for human erythroid progenitor cells. Baculovirus-derived parvovirus antigen can substitute for scarce viral antigen in immunoassays and should be suitable as a human vaccine.
Angiotensin Blockade Prevents Type 2 Diabetes by Formation of Fat Cells (2002)

Obesity is the prime risk factor for the development of type 2 diabetes. Recent clinical trials have shown that blockade of the renin-angiotensin system, either by inhibiting the angiotensin-converting enzyme or blocking the angiotensin type 1 receptor, may substantially lower the risk for type 2 diabetes. The mechanism underlying this effect is unknown. Based on our recent observation that angiotensin II markedly inhibits adipogenic differentiation of human adipocytes via the angiotensin type I receptor and that expression of angiotensin II-forming enzymes in adipose tissue is inversely correlated with insulin sensitivity, we propose the hypothesis that blockade of the renin-angiotensin system prevents diabetes by promoting the recruitment and differentiation of adipocytes. Increased formation of adipocytes would counteract the ectopic deposition of lipids in other tissues (muscle, liver, pancreas), thereby improving insulin sensitivity and preventing the development of type 2 diabetes.
Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas. (1997)

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are ideal neoplasms to study clonal progression and genetic diversity because of their large size and prominent intraductal component. We microdissected 55 histologically defined areas from 13 IPMNs, extracted the DNA from each, and performed polymerase chain reaction (PCR)-based microsatellite analysis to detect loss of heterozygosity on chromosome arms 1p, 3p, 6q, 8p, 9p, 17p, 18q, and 22q. LOH was identified at 1p in two cases, at 3p in four cases, at 6q in seven cases, at 8p in four cases, at 9p in eight cases, at 17p in five cases, at 18q in five cases, and at 22q in one of the IPMNs examined. In one of the IPMNs, the allelic losses were uniform throughout multiple microdissected areas, and in four of the IPMNs, there was evidence of clonal progression. In contrast, in three of the IPMNs, substantial allelic heterogeneity was seen. This remarkable heterogeneity may, in part, be due to the slow growth rate of these neoplasms.
Structure–activity studies on magainins and other host defense peptides (1995)

Host defense peptides are widely distributed in nature, being found in species from bacteria to humans. The structures of these peptides from insects, horseshoe crabs, frogs, and mammals are known to have the common features of a net cationic charge due to the presence of multiple Arg and Lys residues and in most cases the ability to form amphipathic structures. These properties are important for the mechanism of action that is thought to be a nonreceptor-mediated interaction with the anionic phospholipids of the target cell followed by incorporation into the membrane and disruption of the membrane structure. Host defense peptides have been shown to have broad spectrum antimicrobial activity, able to kill most strains of bacteria as well as some fungi, protozoa, and in addition, many types of tumor cells. Specificity for pathogenic cells over host cells is thought to be due to the composition of the cell membranes, with an increased proportion of anionic phospholipids making the pathogen more susceptible and the presence of cholesterol making the host membranes more resistant. Structure-activity relationship studies have been performed on insect cecropins and apidaecins, horseshoe crab tachyplesins and polyphemusins, and the frog magainins, CPFs (caerulein precursor fragments) and PGLa. In general, changes that increased the basicity and stabilized the amphipathic structure have increased the antimicrobial activity; however, as the peptides become more hydrophobic the degree of specificity decreases. One magainin-2 analogue, MSI-78, has been developed by Magainin Pharmaceuticals as a topical antiinfective and is presently in clinical trials for the treatment of infected diabetic foot ulcers.
Chaperonin filaments: The archaeal cytoskeleton? (1997)

Chaperonins are high molecular mass double-ring structures composed of 60-kDa protein subunits. In the hyperthermophilic archaeon Sulfolobus shibatae the two chaperonin proteins represent approximately 4% of its total protein and have a combined intracellular concentration of >30 mg/ml. At concentrations >/= 0.5 mg/ml purified chaperonins form filaments in the presence of Mg2+ and nucleotides. Filament formation requires nucleotide binding (not hydrolysis), and occurs at physiological temperatures in biologically relevant buffers, including a buffer made from cell extracts. These observations suggest that chaperonin filaments may exist in vivo and the estimated 4600 chaperonins per cell suggest that such filaments could form an extensive cytostructure. We observed filamentous structures in unfixed, uranyl-acetate-stained S. shibatae cells, which resemble the chaperonin filaments in size and appearance. ImmunoGold (Janssen) labeling using chaperonin antibodies indicated that many chaperonins are associated with insoluble cellular structures and these structures appear to be filamentous in some areas, although they could not be uranyl-acetate-stained. The existence of chaperonin filaments in vivo suggests a mechanism whereby their protein-folding activities can be regulated. More generally, the filaments themselves may play a cytoskeletal role in Archaea.
The Microbiology of Recurrent Rhinosinusitis After Endoscopic Sinus Surgery (1999)

A wide range of bacteria may be present in the infected post-ESS sinus cavity, with a considerable population of gram-negative organisms, including Pseudomonas species. Beta-Lactamase-producing organisms continue to be prevalent in postoperative sinus infections. Culture and sensitivity analyses of pathologic secretions may identify drug-resistant organisms or organisms related to difficult-to-treat infections in exacerbations of chronic rhinosinusitis in the postoperative setting.
Suppression of Sucrose Synthase Gene Expression Represses Cotton Fiber Cell Initiation, Elongation, and Seed Development (2003)

Cotton is the most important textile crop as a result of its long cellulose-enriched mature fibers. These single-celled hairs initiate at anthesis from the ovule epidermis. To date, genes proven to be critical for fiber development have not been identified. Here, we examined the role of the sucrose synthase gene (Sus) in cotton fiber and seed by transforming cotton with Sus suppression constructs. We focused our analysis on 0 to 3 days after anthesis (DAA) for early fiber development and 25 DAA, when the fiber and seed are maximal in size. Suppression of Sus activity by 70% or more in the ovule epidermis led to a fiberless phenotype. The fiber initials in those ovules were fewer and shrunken or collapsed. The level of Sus suppression correlated strongly with the degree of inhibition of fiber initiation and elongation, probably as a result of the reduction of hexoses. By 25 DAA, a portion of the seeds in the fruit showed Sus suppression only in the seed coat fibers and transfer cells but not in the endosperm and embryo. These transgenic seeds were identical to wild-type seeds except for much reduced fiber growth. However, the remaining seeds in the fruit showed Sus suppression both in the seed coat and in the endosperm and embryo. These seeds were shrunken with loss of the transfer cells and were <5% of wild-type seed weight. These results demonstrate that Sus plays a rate-limiting role in the initiation and elongation of the single-celled fibers. These analyses also show that suppression of Sus only in the maternal seed tissue represses fiber development without affecting embryo development and seed size. Additional suppression in the endosperm and embryo inhibits their own development, which blocks the formation of adjacent seed coat transfer cells and arrests seed development entirely.
Bone Toxicity of Locally Applied Aminoglycosides (1995)

The effect of tobramycin on osteoblasts was studied. Osteoblast-like cells from the MG-63 human osteosarcoma cell line were grown in antibiotic-free media and exposed to concentrations of tobramycin: first at order of magnitude intervals between 0 and 10,000 micrograms/ml, and then at closer intervals between 100 and 1,000 micrograms/ml to more accurately define toxic levels. Cell number and 3H-thymidine incorporation at 0, 24 and 72 h were determined. Similarly, primary cultures of rat osteoblasts were exposed to the same concentrations of tobramycin to confirm the validity of the MG-63 cell line as a model for nontransformed cells. The results of this study demonstrate that local levels of tobramycin of < or = 200 micrograms/ml have little or no effect on osteoblast replication. Concentrations of 400 micrograms/ml significantly decreased cell replication, and concentrations of 10,000 micrograms/ml caused cell death. Results obtained with primary rat osteoblast cultures were similar to those obtained from the MG-63 cultures at the tested tobramycin concentrations.
Structure and Hemimethylated CpG Binding of the SRA Domain from Human UHRF1 (2008)

Human UHRF1 (ubiquitin-like PHD and RING finger 1) functions to maintain CpG DNA methylation patterns through DNA replication by co-localizing with the DNA methyltransferase DNMT1 at chromatin in mammals. Recent studies show that UHRF1 binds selectively to hemimethylated CpG via its conserved SRA (SET- and RING finger-associated) domain. However, the underlying molecular mechanism is not known. Here, we report a 1.95 A resolution crystal structure of the SRA domain of human UHRF1. Using NMR structure-guided mutagenesis, electrophoretic mobility shift assay, and fluorescence anisotropy analysis, we determined key amino acid residues for methyl-DNA binding that are conserved in the SRA domain.
Identification of TRAIL as an Interferon Regulatory Factor 3 Transcriptional Target (2005)

Interferon production and apoptosis in virus-infected cells are necessary to prevent progeny virus production and to eliminate infected cells. Paramyxovirus infection induces apoptosis through interferon regulatory factor 3 (IRF-3), but the exact mechanism of how IRF-3 functions is unknown. We show that IRF-3 is involved in the transcriptional induction of TRAIL, a key player in the apoptosis pathway. IRF-3 upregulates TRAIL transcription following viral infection and binds an interferon-stimulated response element in the TRAIL promoter. The mRNA for TRAIL and its receptor, DR5, are induced following viral infection. These studies identify TRAIL as a novel IRF-3 transcriptional target.
ChemInform Abstract: Modern Machine‐Aided Methods of Oligodeoxyribonucleotide Synthesis (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Pseudomonas fluorescens CHA0 Produces Enantio-pyochelin, the Optical Antipode of the Pseudomonas aeruginosa Siderophore Pyochelin (2007)

The siderophore pyochelin is made by a thiotemplate mechanism from salicylate and two molecules of cysteine. In Pseudomonas aeruginosa, the first cysteine residue is converted to its D-isoform during thiazoline ring formation whereas the second cysteine remains in its L-configuration, thus determining the stereochemistry of the two interconvertible pyochelin diastereoisomers as 4'R, 2''R, 4''R (pyochelin I) and 4'R, 2''S, 4''R (pyochelin II). Pseudomonas fluorescens CHA0 was found to make a different stereoisomeric mixture, which promoted growth under iron limitation in strain CHA0 and induced the expression of its biosynthetic genes, but was not recognized as a siderophore and signaling molecule by P. aeruginosa. Reciprocally, pyochelin promoted growth and induced pyochelin gene expression in P. aeruginosa, but was not functional in P. fluorescens. The structure of the CHA0 siderophore was determined by mass spectrometry, thin-layer chromatography, NMR, polarimetry, and chiral HPLC as enantio-pyochelin, the optical antipode of the P. aeruginosa siderophore pyochelin. Enantio-pyochelin was chemically synthesized and confirmed to be active in CHA0. Its potential biosynthetic pathway in CHA0 is discussed.
Discriminative training and maximum entropy models for statistical machine translation (2001)

We present a framework for statistical machine translation of natural languages based on direct maximum entropy models, which contains the widely used source-channel approach as a special case. All knowledge sources are treated as feature functions, which depend on the source language sentence, the target language sentence and possible hidden variables. This approach allows a baseline machine translation system to be extended easily by adding new feature functions. We show that a baseline statistical machine translation system is significantly improved using this approach.
Differential and common recognition of the catalytic sites of the cGMP-dependent and cAMP-dependent protein kinases by inhibitory peptides derived from the heat-stable inhibitor protein. (1986)

Synthetic peptides corresponding to the active domain of the heat-stable inhibitor protein of cAMP-dependent protein kinase (Cheng, H.-C., Kemp, B. E., Pearson, R. B., Smith, A. J., Misconi, L., Van Patten, S. M., and Walsh, D. A. (1986) J. Biol. Chem. 261, 989-992) were tested as inhibitors of cGMP-dependent protein kinase. The peptides themselves were not substrates. cGMP-dependent protein kinase activity was assayed using histone H2B and two synthetic peptide substrates. Consistent with previous observations of other peptide inhibitors of this enzyme (Glass, D. B. (1983) Biochem. J. 213, 159-164), the inhibitory peptides had no effect on the phosphorylation of histone H2B, but they competitively inhibited cGMP-dependent phosphorylation of the two peptide substrates. The parent inhibitor peptide, PKI(5-24)amide, and a series of analogs had Ki (or IC50) values for cGMP-dependent protein kinase in the range of 15-190 microM. In contrast to their effects on the cAMP-dependent protein kinase, the inhibitory peptides were substantially less potent with cGMP-dependent protein kinase, and potency was reduced by the presence of the NH2-terminal residues (residues 5-13). We conclude that the two protein kinases share a recognition of the basic amino acid cluster within the pseudosubstrate region of the peptide, but that the cGMP-dependent protein kinase does not recognize additional NH2-terminal determinants that make the inhibitor protein extremely potent toward the cAMP-dependent enzyme. Even- when tested at high concentrations and with peptide substrates, the native inhibitor protein did not inhibit cGMP-dependent protein kinase under assay conditions in which the peptides derived from it were inhibitory. Thus, the native inhibitor protein appears to have structural features which block interaction with the cGMP-dependent enzyme and enhance its selectivity for cAMP-dependent protein kinase.
Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. (1986)

We used radioligand binding techniques and measurement of beta-agonist-mediated positive inotropic responses in isolated cardiac tissue to examine beta-adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. In tissue derived from 48 human hearts the receptor subtypes identified in nonfailing ventricle by radioligand binding were beta 1 (77%) and beta 2 (23%), with no evidence of an "atypical" beta-adrenergic receptor. In failing left ventricle the beta 1:beta 2 ratio was markedly different, i.e., 60:38. This decrease in the beta 1 proportion and increase in the beta 2 proportion in the failing ventricles were due to a 62%, "selective" down-regulation of the beta 1 subpopulation, with little or no change in beta 2 receptors. In muscle bath experiments in isolated trabeculae derived from nonfailing and failing right ventricles, both beta 1- and beta 2-adrenergic receptors were coupled to a positive inotropic response. In nonfailing myocardium, beta 1 responses predominated, as the selective beta 1 agonist denopamine produced a response that was 66% of the total contractile response of isoproterenol. In heart failure the beta 1 component was markedly decreased, while the beta 2 component was not significantly diminished. Moreover, in heart failure the beta 2 component increased in prominence, as the contractile response to the selective beta 2 agonist zinterol increased from a minority (39%) to a majority (60%) of the total response generated by isoproterenol. We conclude that failing human ventricular myocardium contains a relatively high proportion of beta 2 receptors, due to selective down-regulation of beta 1 receptors. As a result, in the failing human heart the beta 2-receptor subpopulation is a relatively important mediator of inotropic support in response to nonselective beta-agonist stimulation and is available for inotropic stimulation by selective beta 2 agonists.
Transverse correlation length in thin film media (1992)

A method to estimate a transverse correlation length lambda in magnetic thin-film media has been developed. Using a pseudomicrotrack (or filamentary track) analysis, expressions for estimating lambda of the media have been derived. lambda can be determined from the slope of the correlation coefficient of read back signals read at different lateral positions. It was observed that lambda does not strongly depend on the remanent magnetic state for a single-layer medium with strong intergranular coupling but decreases significantly near demagnetization for a multilayer medium.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Event-based hyperspectral EELS: towards nanosecond temporal resolution (2022)

The acquisition of a hyperspectral image is nowadays a standard technique used in the Scanning Transmission Electron Microscope. It relates the spatial position of the electron probe to the spectral data associated with it [1]. In the case of Electron Energy Loss Spectroscopy (EELS), frame-based hyperspectral acquisition is much slower than the achievable rastering time of the scan unit (SU), which sometimes leads to undesirable effects in the sample, such as electron irradiation damage, that goes unperceived during frame acquisition In this work, we have developed an event-based hyperspectral EELS by using a Timepix3 application-specific integrated circuit detector with two supplementary timeto-digital (TDC) lines embedded. In such a system, electron events are characterized by their positional and temporal coordinates [3], but TDC events only by temporal ones. By sending reference signals from the SU to the TDC line To exemplify the possibilities behind event-based hyperspectral EELS, we have studied the decomposition of calcite (CaCO 3 ) into calcium oxide (CaO) and carbon dioxide (CO 2 ) under the electron beam irradiation (Figure The present work has been recently published in ref.
Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease (2010)

Our data suggest that inhibition of mTOR by rapamycin, an intervention that extends lifespan in mice, can slow or block AD progression in a transgenic mouse model of the disease. Rapamycin, already used in clinical settings, may be a potentially effective therapeutic agent for the treatment of AD.
Blood Monocytes: Development, Heterogeneity, and Relationship with Dendritic Cells (2009)

Monocytes are circulating blood leukocytes that play important roles in the inflammatory response, which is essential for the innate response to pathogens. But inflammation and monocytes are also involved in the pathogenesis of inflammatory diseases, including atherosclerosis. In adult mice, monocytes originate in the bone marrow in a Csf-1R (MCSF-R, CD115)-dependent manner from a hematopoietic precursor common for monocytes and several subsets of macrophages and dendritic cells (DCs). Monocyte heterogeneity has long been recognized, but in recent years investigators have identified three functional subsets of human monocytes and two subsets of mouse monocytes that exert specific roles in homeostasis and inflammation in vivo, reminiscent of those of the previously described classically and alternatively activated macrophages. Functional characterization of monocytes is in progress in humans and rodents and will provide a better understanding of the pathophysiology of inflammation.