gebhart/patrepeval huggingface dataset:
Protection of pancreatic beta-cell by the potential antioxidant bis-o-hydroxycinnamoyl methane, analogue of natural curcuminoid in experimental diabetes. (2004)

The experimental drug bis-o-hydroxycinnamoylmethane enhances the antioxidant defense against reactive oxygen species produced under hyperglycemic conditions and thus protects the pancreatic b -cell against loss and exhibits antidiabetic property.
Fibronectin receptor modulates cyclin-dependent kinase activity. (1992)

The high affinity fibronectin receptor (FNR) is expressed by hematopoietic cells, fibroblasts, and proliferating epidermal cells. Expression of this integrin is altered by chemical and viral transformation, suggesting that FNR dysfunction may play a role in growth control. This study demonstrates that exposing FA-K562 cells to glycine-arginine-glycine-aspartate-serine (GRGDS), a peptide ligand of the FNR, specifically stimulates p34/cdc2- and cyclin A-associated kinase activities. This occurs within 2 h of peptide addition. The 110-kDa form of the retinoblastoma protein appears within 3 h of GRGDS addition, consistent with activation of a G1/S kinase. DNA staining profiles demonstrate that GRGDS induces cell cycle progression within 24 h. Increased anchorage-independent growth is subsequently observed in GRGDS-treated FA-K562 cells. The control peptide, GRGES, which cannot bind the FNR, has none of these effects. This demonstrates that an extracellular integrin ligand can regulate cell proliferation. Furthermore, these results suggest that integrins link the extracellular environment and intracellular growth regulators.
Replacement of the F and G Proteins of Respiratory Syncytial Virus (RSV) Subgroup A with Those of Subgroup B Generates Chimeric Live Attenuated RSV Subgroup B Vaccine Candidates (1999)

Human respiratory syncytial virus (RSV) exists as two antigenic subgroups, A and B, both of which should be represented in a vaccine. The F and G glycoproteins are the major neutralization and protective antigens, and the G protein in particular is highly divergent between the subgroups. The existing system for reverse genetics is based on the A2 strain of RSV subgroup A, and most efforts to develop a live attenuated RSV vaccine have focused on strain A2 or other subgroup A viruses. In the present study, the development of a live attenuated subgroup B component was expedited by the replacement of the F and G glycoproteins of recombinant A2 virus with their counterparts from the RSV subgroup B strain B1. This gene replacement was initially done for wild-type (wt) recombinant A2 virus to create a wt AB chimeric virus and then for a series of A2 derivatives which contain various combinations of A2-derived attenuating mutations located in genes other than F and G. The wt AB virus replicated in cell culture with an efficiency which was comparable to that of the wt A2 and B1 parents. AB viruses containing temperature-sensitive mutations in the A2 background exhibited levels of temperature sensitivity in vitro which were similar to those of A2 viruses bearing the same mutations. In chimpanzees, the replication of the wt AB chimera was intermediate between that of the A2 and B1 wt viruses and was accompanied by moderate rhinorrhea, as previously seen in this species. An AB chimeric virus, rABcp248/404/1030, which was constructed to contain a mixture of attenuating mutations derived from two different biologically attenuated A2 viruses, was highly attenuated in both the upper and lower respiratory tracts of chimpanzees. This attenuated AB chimeric virus was immunogenic and conferred a high level of resistance on chimpanzees to challenge with wt AB virus. The rABcp248/404/1030 chimeric virus is a promising vaccine candidate for RSV subgroup B and will be evaluated next in humans. Furthermore, these results suggest that additional attenuating mutations derived from strain A2 can be inserted into the A2 background of the recombinant chimeric AB virus as necessary to modify the attenuation phenotype in a reasonably predictable manner to achieve an optimal balance between attenuation and immunogenicity in a virus bearing the subgroup B antigenic determinants.
Development of disease-resistant rice using regulatory components of induced disease resistance (2014)

Infectious diseases cause huge crop losses annually. In response to pathogen attacks, plants activate defense systems that are mediated through various signaling pathways. The salicylic acid (SA) signaling pathway is the most powerful of these pathways. Several regulatory components of the SA signaling pathway have been identified, and are potential targets for genetic manipulation of plants' disease resistance. However, the resistance associated with these regulatory components is often accompanied by fitness costs; that is, negative effects on plant growth and crop yield. Chemical defense inducers, such as benzothiadiazole and probenazole, act on the SA pathway and induce strong resistance to various pathogens without major fitness costs, owing to their 'priming effect.' Studies on how benzothiadiazole induces disease resistance in rice have identified WRKY45, a key transcription factor in the branched SA pathway, and OsNPR1/NH1. Rice plants overexpressing WRKY45 were extremely resistant to rice blast disease caused by the fungus Magnaporthe oryzae and bacterial leaf blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo), the two major rice diseases. Disease resistance is often accompanied by fitness costs; however, WRKY45 overexpression imposed relatively small fitness costs on rice because of its priming effect. This priming effect was similar to that of chemical defense inducers, although the fitness costs were amplified by some environmental factors. WRKY45 is degraded by the ubiquitin-proteasome system, and the dual role of this degradation partly explains the priming effect. The synergistic interaction between SA and cytokinin signaling that activates WRKY45 also likely contributes to the priming effect. With a main focus on these studies, I review the current knowledge of SA-pathway-dependent defense in rice by comparing it with that in Arabidopsis, and discuss potential strategies to develop disease-resistant rice using signaling components.
Preliminary studies on vaccination of rhesus monkeys with irradiated sporozoites of Plasmodium knowlesi and characterization of surface antigens of these parasites. (1979)

Studies were conducted to develop an effective method of inducing protection against sporozoite-induced malaria in a primate system and to obtain information regarding the surface membrane antigens of sporozoites. Immunization of rhesus monkeys was performed with gamma-irradiated sporozoites of Plasmodium knowlesi. Levels of antisporozoite antibodies were monitored by immunofluorescence, sporozoite neutralization, and the circumsporozoite precipitate reaction, and appeared to correlate well with protection. Only the intravenous route was effective in inducing both protection and antisporozoite antibodies. Immunization with sporozoites mixed with Freund's complete adjuvant failed completely to induce protection and resulted in a minimal antibody response. Mechanisms of resistance to sporozoites probably involve the interaction of the host's immune system with the parasite's surface antigen(s). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of surface-labelled, partially purified sporozoites followed by autoradiography revealed the presence of a small number of labelled proteins in the extract. Immunoprecipitation with specific antisera to P. berghei detected primarily one of these membrane components, with an apparent molecular weight of 41 000. The molecular weight of this main surface antigen in sporozoites of P. berghei was different from that in sporozoites of P. knowlesi.
Effect of caffeine and tannins on cultivation and fructification of Pleurotus on coffee husks (2006)

The objective of this work was to study the effect of caffeine and tannins on Pleurotus sp. cultivation and to evaluate the feasibility of using coffee husks as substrate for mushroom cultivation. Eight strains of P. ostreatus and two strains of P. sajor-caju were screened on a medium prepared from agar extract of coffee husk. Based on best mycelial growth and biomass production, the strain P. ostreatus LPB 09 was selected for detailed studies. With the increase of caffeine concentration, the mycelial growth and the biomass production decreased, and no growth was observed when concentration of caffeine was 2500 mg/L. Furthermore, Pleurotus did not degrade the caffeine, but absorbed it. Tannin under 100 mg/L in the medium stimulated the growth of mycelia, but above 500 mg/L it had a negative effect. When the concentration reached 1000 mg/L, the fungus still survived and showed a certain tolerance to it. No tannic acid was found in the mycelia, but its concentration decreased in the medium. This fact confirmed that Pleurotus had the capacity of degrading tannic acid. Fructification occurred after 20 days of inoculation and the biological efficiency reached about 97% after 60 days. Caffeine content in the husk after cultivation was reduced to 60.7% and tannins to 79.2%. The results indicated the feasibility of using coffee husk without any pretreatment for the cultivation of Pleurotus.
A geodesic-active-contour-based variational model for short-axis cardiac MR image segmentation (2012)

We propose a novel geodesic-active-contour-based (GAC-based) variational model that uses two level-set functions to segment the right and left ventricles and the epicardium in short-axis magnetic resonance (MR) images. For the right ventricle, the myocardial wall is typically very thin and hard to identify using the resolution of existing MR scanners. We propose to use two level sets to identify both the endocardial wall by pushing away one level-set function from another, in the setting of the edge-driven GAC model with a new edge detection function. Existing edge detection functions have strict restrictions on the location of initial contours. We develop a new edge detection function that relaxes this restriction and propose an iterative method that uses a sequence of edge detection functions to minimize the energy of our model successively. Experimental results are presented to validate the effectiveness of the proposed model.
FTDP-17: An early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation (1999)

Recently, mutations in the tau gene on chromosome 17 were found causative for autosomal dominantly inherited frontotemporal dementia and parkinsonism (FTDP-17). We describe a family carrying a missense mutation at nucleotide 1137 C --> T, resulting in the amino acid substitution P301S. Methods of investigations include clinical, electrophysiological, and imaging techniques. This kindred presents with a novel phenotype characterized by an early onset of rapidly progressive frontotemporal dementia and parkinsonism in combination with epileptic seizures. We define the dopaminergic deficits as being predominantly presynaptic by the use of single-photon emission computed tomography with a dopamine transporter ligand. The association of this early-onset phenotype with P301S mutation is not entirely consistent with current criteria for the diagnosis of frontotemporal dementias and may encourage the search for tau mutations in diseases similar but not identical to FTDP-17. Also, the change from proline to serine suggests that this mutation might contribute to tau hyperphosphorylation.
Closure Properties of Bulgarian Clinical Text (2013)

Sublanguages are specialized genres of language associated with specific domains and document types. When sublanguages can be recognized and adequately characterized, they are useful for a variety of types of natural language processing applications. Although there are sublanguage studies related to languages other than English, all previous work on sublanguage recognition has focused on sublanguages related to general English. This paper tests whether a sublanguage detecting technique developed for English can be applied to another language. Bulgarian clinical documents are an excellent test case, because of a number of unique linguistic properties that affect their lexical and morphological characteristics. Bulgarian clinical documents were studied with respect to their closure properties and were found to fit the sublanguage model and exhibit characteristics like those noted for sublanguages related to English. It was also confirmed that the clinical sublanguage phenomenon is not a coincidental phenomenon of English, but applies to other languages as well. Implications of this fact for natural language processing are proposed.
Quantitative analysis of Argonaute protein reveals microRNA-dependent localization to stress granules (2006)

Argonaute proteins associate with microRNAs (miRNAs) that bind mRNAs through partial base-pairings to primarily repress translation in animals. A fraction of Argonaute proteins and miRNAs biochemically cosediment with polyribosomes, yet another fraction paradoxically accumulates in ribosome-free processing bodies (PBs) in the cytoplasm. In this report, we give a quantitative account of the Argonaute protein localization and dynamics in living cells in different cellular states. We find that the majority of Argonaute is distributed diffusely in the cytoplasm, and, when cells are subjected to stress, Argonaute proteins accumulate to newly assembled structures known as stress granules (SGs) in addition to PBs. Argonaute proteins displayed distinct kinetics at different structures: exchange faster at SGs and much slower at PBs. Further, miRNAs are required for the Argonaute protein localization to SGs but not PBs. These quantitative kinetic data provide insights into miRNA-mediated repression.
Development of a simple but effective cancer vaccine consisting of an antigen and a cationic lipid (2007)

Human papillomavirus (HPV) oncoproteins E6 and E7 which are constitutively expressed in cervical cancer cells are ideal targets for developing immunotherapies for treatment of existing HPV-associated carcinoma. In this project, we developed a simple, safe, and efficient, peptide-based therapeutic cancer vaccine, DOTAP/E7 complex, which comprises only two molecules: a DOTAP cationic lipid and an MHC class I-restricted peptide antigen derived from HPV-16 E7 protein. TC-1 cell line which is HPV-16 E7+ was used as a tumor model in an H-2b murine system. Tumor-bearing mice showed significant tumor inhibition following a single injection of DOTAP/E7 at the optimal lipid dose, suggesting that DOTAP liposome alone can be a potent adjuvant. E7 peptide formulated with DOTAP was taken up by dendritic cells (DC) and induced DC activation and migration to the draining lymph node (DLN), eliciting antigen-specific CD8+ cytotoxic T lymphocyte (CTL) responses. The mechanism of DOTAP as a vaccine adjuvant was revealed by DOTAP-mediated reactive oxygen species (ROS) production in DC. At the optimal lipid dose, DOTAP/E7 generates an adequate level of ROS for the initiation of the vaccine mechanism. In addition, we have improved the vaccine formulation by incorporation of E7-lipopeptide instead of the water-soluble native E7 peptide. The improved DOTAP/E7-lipopeptide vaccine showed a significantly enhanced therapeutic effect, including CTL response and anti-tumor activity. The vaccine was also effective for suppression of tumor growth in later stages of tumor progression, suggesting applications for advanced cancer treatment. Furthermore, we extended the studies of the vaccine efficacy observed in the mouse model to human cells in vitro. Instead of H-2Db-restricted peptide, an HLA-A2-restricted E7 peptide epitope (hE7) was formulated into the liposome. In vitro stimulation of naïve HLA-A2+ human T lymphocytes by DOTAP/hE7-activated autologous DC elicited a stronger clonal T cell proliferation and higher HPV-specific CTL response compared to those stimulated with DC pulsed with hE7 peptide alone. The in vivo CTL and anti-tumor activity induced by DOTAP/hE7 vaccine were demonstrated in an HLA-A2 transgenic mouse model. Overall, our data suggest that DOTAP/hE7 is a potent therapeutic cancer vaccine formulation with potential for clinical applications for the treatment of HPV-related neoplasia.
Cell cycle regulation by the intrinsically disordered proteins p21 and p27 (2012)

Today, it is widely accepted that proteins that lack highly defined globular three-dimensional structures, termed IDPs (intrinsically disordered proteins), play key roles in myriad biological processes. Our understanding of how intrinsic disorder mediates biological function is, however, incomplete. In the present paper, we review disorder-mediated cell cycle regulation by two intrinsically disordered proteins, p21 and p27. A structural adaptation mechanism involving a stretchable dynamic linker helix allows p21 to promiscuously recognize the various Cdk (cyclin-dependent kinase)-cyclin complexes that regulate cell division. Disorder within p27 mediates transmission of an N-terminal tyrosine phosphorylation signal to a C-terminal threonine phosphorylation, constituting a signalling conduit. These mechanisms are mediated by folding upon binding p21/p27's regulatory targets. However, residual disorder within the bound state contributes critically to these functional mechanisms. Our studies provide insights into how intrinsic protein disorder mediates regulatory processes and opportunities for designing drugs that target cancer-associated IDPs.
Structural Basis for Treating Tumor Necrosis Factor α (TNFα)-associated Diseases with the Therapeutic Antibody Infliximab (2013)

The structure may lead to understanding the mechanism of mAb anti-TNFα Monoclonal antibody (mAb) drugs have been widely used for treating tumor necrosis factor α (TNFα)-related diseases for over 10 years. Although their action has been hypothesized to depend in part on their ability to bind precursor cell surface TNFα, the precise mechanism and the epitope bound on TNFα remain unclear. In the present work, we report the crystal structure of the infliximab Fab fragment in complex with TNFα at a resolution of 2.6 Å. The key features of the TNFα E-F loop region in this complex distinguish the interaction between infliximab and TNFα from other TNF-receptor structures, revealing the mechanism of TNFα inhibition by overlapping with the TNFα-receptor interface and indicating the crucial role of the E-F loop in the action of this therapeutic antibody. This structure also indicates the formation of an aggregated network for the activation of complement-dependent cytolysis and antibody-dependent cell-mediated cytotoxicity, which result in development of granulomatous infections through TNFα blockage. These results provide the first experimental model for the interaction of TNFα with therapeutic antibodies and offer useful information for antibody optimization by understanding the precise molecular mechanism of TNFα inhibition.
Ligand occupancy of the alpha-V-beta3 integrin is necessary for smooth muscle cells to migrate in response to insulin-like growth factor. (1996)

Smooth muscle cells (SMCs) have been shown to migrate in response to insulin-like growth factor I (IGF-I). However, the mechanism mediating this response has not been determined. The migration rates of porcine and human vascular SMCs were assessed in a monolayer wounding assay. IGF-I and IGF-II induced increases of 141% and 97%, respectively, in the number of cells that migrated in 4 days. The presence of 0.2% fetal bovine serum in the culture medium was necessary for the IGFs to stimulate migration over uncoated plastic surfaces. However, if vitronectin was used as the substratum, IGF-I stimulated migration by 162% even in the absence of serum. To determine the role of integrins in mediating this migration, SMC surface proteins were labeled with 125I and immunoprecipitated with specific anti-integrin antibodies. Integrins containing alpha-V (vitronectin receptor), alpha5 (fibronectin receptor), and alpha3 (collagen/laminin receptor) subunits were the most abundant. IGF-I treatment caused a 73% reduction in alpha5-integrin subunit protein and a 25% increase in alpha-V subunit. More importantly, ligand binding of alpha-V-beta3 was increased by 2.4-fold. We therefore examined whether the function of the alpha-V-beta3 integrin was important for IGF-I-mediated migration. The disintegrin kistrin was shown by affinity crosslinking to specifically bind with high affinity to alpha-V-beta3 and not to alpha5-beta1 or other abundant integrins. The related disintegrin echistatin specifically inhibited 125I-labeled kistrin binding to alpha-V-beta3, while a structurally distinct disintegrin, decorsin, had 1000-fold lower affinity. The addition of increasing concentrations of either kistrin or echistatin inhibited IGF-I-induced migration, whereas decorsin had a minimal effect. The potency of these disintegrins in inhibiting IGF-I-induced migration paralleled their apparent affinity for the alpha-V integrin. Furthermore, an alpha-V-beta3 blocking antibody inhibited SMC migration by 80%. In summary, vitronectin receptor activation is a necessary component of IGF-I-mediated stimulation of smooth muscle migration, and alpha-V-beta3 integrin antagonists appear to be important reagents for modulating this process.
Insulinlike Growth Factor-I???Mediated Migration and Invasion of Human Colon Carcinoma Cells Requires Activation of c-Met and Urokinase Plasminogen Activator Receptor (2005)

IGF-I and HGF cooperate to induce migration and invasion of CRC cells, and c-Met and uPA/uPAR are required for IGF-I-mediated migration and invasion. In our in vitro model of CRC migration and invasion, uPA and uPAR appear to be downstream of IGF-IR and c-Met and are required for migration and invasion. Elucidation of the pathways that contribute to tumor progression and metastasis should provide a foundation for the rational development and use of targeted therapies for CRC.
Software metrics (2nd ed.): a rigorous and practical approach (1997)

The half-life of an insecticide on a treated object can be used as a crucial test for evaluating the residual effect. On cotton and nylon bednets, the half-life of deltamethrin was 65.6 and 55.4 days, whereas the half-life of permethrin on cotton and nylon bednets was 35.0 and 27.4 days. A deltamethrin-impregnated bednet (10 mg/m2) is effective for 6-7 months and costs less than DDT residual spraying (2g/m2) on the inner walls of rooms.
Pre-tRNA splicing in a nuclear extract from human leukaemia cells: separation of endonuclease and ligase activities (1988)

Journal Article Pre-tRNA splicing in a nuclear extract from human leukaemia cells: separation of endonuclease and ligase activities Get access Kurt Herrenknecht, Kurt Herrenknecht * Institut für Biochemie, Bayerische Julius-Maximilians-UniversitätRöntgenring 11, D-8700 Würzburg, FRG * Present address: Max-Planck-Institut für Immunbiologie, Stübeweg 51, D—7800 Freiburg, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans van Tol, Hans van Tol Institut für Biochemie, Bayerische Julius-Maximilians-UniversitätRöntgenring 11, D-8700 Würzburg, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans J. Gross Hans J. Gross Institut für Biochemie, Bayerische Julius-Maximilians-UniversitätRöntgenring 11, D-8700 Würzburg, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 16, Issue 15, 11 August 1988, Pages 7713–7714, https://doi.org/10.1093/nar/16.15.7713 Published: 11 August 1988 Article history Received: 17 June 1988 Revision received: 14 July 1988 Accepted: 14 July 1988 Published: 11 August 1988