gebhart/patrepeval huggingface dataset:
Plasminogen Activator Inhibitor-1 Induction after Experimental Intracerebral Hemorrhage (2002)

Serine proteases, such as thrombin and tissue-type plasminogen activator, play an important role in brain injury after intracerebral hemorrhage and other neurologic disorders. Plasminogen activator inhibitor-1 is one of the serine protease inhibitors, or serpins. The balance between serine proteases and serpins may affect the outcome of intracerebral hemorrhage. The purpose of this study was to determine whether plasminogen activator inhibitor-1 and tissue-type plasminogen activator are upregulated after intracerebral hemorrhage and the role that thrombin plays in that induction. Plasminogen activator inhibitor-1 protein levels were upregulated after intracerebral hemorrhage. Brain plasminogen activator inhibitor-1 content also increased after thrombin infusion in a dose-dependent manner. Hirudin, a specific thrombin inhibitor, blocked the upregulation of plasminogen activator inhibitor-1 after intracerebral hemorrhage. Time courses showed that plasminogen activator inhibitor-1 levels around the hematoma peaked at the first day. Plasminogen activator inhibitor-1-positive cells were detected in the perihematomal area and the ipsilateral basal ganglia after thrombin infusion, but not in the contralateral hemisphere. Plasminogen activator inhibitor-1 messenger RNA levels were increased at 24 hours after intracerebral hemorrhage and after thrombin infusion. However, tissue-type plasminogen activator protein levels were the same in the control, whole-blood, and thrombin-infusion groups. In conclusion, intracerebral hemorrhage and thrombin infusion stimulate plasminogen activator inhibitor-1 but not tissue-type plasminogen activator production in the brain. The upregulation of plasminogen activator inhibitor-1 may be neuroprotective by limiting thrombin or other serine protease-induced toxicity.
Structure-function study of the extracellular domain of the human IFN-alpha receptor (hIFNAR1) using blocking monoclonal antibodies: the role of domains 1 and 2. (1998)

We have performed a structure-function analysis of extracellular domain regions of the human IFN-alpha receptor (hIFNAR1) using mAbs generated by immunizing mice with a soluble hIFNAR1-IgG. Five mAbs described in this study recognize different epitopes as determined by a competitive binding ELISA and by alanine substitution mutant analyses of the hIFNAR1-IgG. Two mAbs, 2E1 and 4A7, are able to block IFN-stimulated gene factor 3 (ISGF3) formation and inhibit the antiviral cytopathic effect induced by several IFN-alpha (IFN-alpha 2/1, -alpha 1, -alpha 2, -alpha 5, and -alpha 8). None of these anti-IFNAR1 mAbs were able to block activity of IFN-beta. mAb 4A7 binds to a domain 1-hIFNAR1-IgG but not to a domain 2-hIFNAR1-IgG, which suggests that its binding region is located in domain 1. The binding of the most potent blocking mAb, 2E1, requires the presence of domain 1 and domain 2. The most critical residue for 2E1 binding is a lysine residue at position 249, which is in domain 2. These findings suggest that both domain 1 and domain 2 are necessary to form a functional receptor and that a region in domain 2 is important. IFN-beta recognizes regions of the hIFNAR complex that are distinct from those important for the IFN-alpha.
Use of murine embryonic fibroblasts to define Toll-like receptor activation and specificity (2004)

Toll-like receptors (TLRs) are critically involved in the innate immune response to bacterial, viral and fungal pathogens. We have studied human peripheral blood mononuclear cells, murine embryonic fibroblasts (MEFs) and a panel of human cell lines, including HEK, HeLa, AGS, ECV304 and U373 cells, for expression of TLR-specific mRNAs and for TLR-ligand dependent cytokine secretion. Peripheral blood cells expressed multiple TLRs; however, many studies have shown that blood contains multiple, heterogeneous cell populations with distinct patterns of TLR expression. Cell lines had variable expression of TLRs, and in most cases lacked TLR2 and TLR8 expression and only weakly expressed mRNAs for TLR5, TLR7 and TLR9. In contrast, MEFs expressed high levels of mRNA for TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8 and TLR9. MEFs were highly responsive to TLR-ligand activation and secreted high levels of both IL-6 and MCP-1 in response to TLR ligands. MEFs from mice with targeted deletions of TLR2, TLR4 and MyD88 demonstrated profound defects in their IL-6 response to their specific ligands, consistent with studies of macrophages and tissues from adult knockout animals. MEF cultures are homogenous and amenable to biochemical analysis and should allow rigorous studies of the contribution of individual TLRs to the innate immune response.
The development of oral vaccines based on live attenuated Salmonella strains (1993)

Safe, live attenuated Salmonella strains can be produced by introducing defined non-reverting mutations into the chromosome. Such rationally attenuated strains have proved to be excellent oral vaccines in several animal species and can therefore be considered as candidate vaccines against invasive salmonellosis in both animals and man. A panel of attenuating lesions is now available from which it is possible to tailor the level of attenuation and hence produce strains with different immunogenic properties. Because of the spectrum of immune responses produced by such Salmonella vaccine strains they have been utilised extensively as vectors for delivering heterologous antigens to the mammalian immune system. We have focussed on the development of a single dose oral tetanus vaccine based on attenuated Salmonella strains expressing a non-toxic, immunogenic protein derived from tetanus toxin (fragment C). Several different expression systems have been used for fragment C and candidate vaccine strains have been constructed that are capable of protecting orally immunised mice against a lethal challenge with tetanus toxin. An oral tetanus vaccine may help to reduce the mortality rate from tetanus in the developing world by overcoming the problems associated with the implementation of vaccine programmes using the current parenteral vaccine.
Dietary Fish and ω-3 Fatty Acid Consumption and Heart Rate Variability in US Adults (2008)

Habitual tuna/other fish and marine omega-3 consumption are associated with specific HRV components in older adults, particularly indices of vagal activity, baroreceptor responses, and sinoatrial node function. Cellular mechanisms and implications for clinical risk deserve further investigation.
The aetiology of otitis media with effusion: a review (2000)

Otitis media with effusion (OME) is the most common cause of deafness in children in the developed world. In this article we aim to present an overview of current research developments on the aetiology of OME and the resulting implications for treatment. In the model we describe, the primary event is inflammation of the middle ear mucosa, usually due to the presence of bacteria. This leads to the release of inflammatory mediators, which cause secretion of a mucin-rich effusion by up-regulating mucin genes. Prolonged stimulation of the inflammatory response and poor mucociliary clearance lead to persistence of the middle ear fluid, giving rise to the clinical presentation of OME. We describe OME in the following sequence: the initial production of the effusion, the composition of the effusion produced, and factors impairing clearance of the effusion.
Role and substrate specificity of the Streptomyces coelicolor RedH enzyme in undecylprodiginine biosynthesis (2008)

The function of RedH from Streptomyces coelicolor as an enzyme that catalyses the condensation of 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC) and 2-undecylpyrrole to form the natural product undecylprodiginine has been experimentally proven, and the substrate specificity of RedH has been probed in vivo by examining its ability to condense chemically-synthesised MBC analogues with 2-undecylpyrrole to afford undecylprodiginine analogues.
Genetic and Biochemical Aspects of Yeast Sterol Regulation Involving 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (1981)

Determinations of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity in haploid strains and diploid hybrids of wild-type Saccharomyces cerevisiae revealed that a genetic basis exists for control of this key regulatory enzyme in which low enzyme activity is phenotypically dominant to high enzyme activity. These observations suggested the existence of an inhibitor of reductase activity or a suppressor of enzyme synthesis. Feeding studies using an early sterol intermediate (mevalonolactone) and end-product sterol (ergosterol) indicated that a secondary regulatory site in this pathway operates to decrease the activity of HMG-CoA reductase. This diminution of activity was paralleled by increases in the accumulation of squalene, suggesting that this intermediate (or another isoprenoid derivative) may also play a significant role in the in vivo regulation of sterol biosynthesis. Lastly, feedback inhibition of HMG-CoA reductase by ergosterol was demonstrated in a yeast mutant which is permeable to this sterol. These studies showed that yeast can serve as a eukaryotic model system for a combined biochemical and genetic investigation into the factors which control the activity of HMG-CoA reductase.
Endocrine resistance in breast cancer: new roles for ErbB3 and ErbB4 (2011)

Endocrine resistance is a major limitation to the successful treatment of estrogen receptor-positive (ER(+)) breast cancer, and the EGFR (epidermal growth factor receptor) and ErbB-2 receptor tyrosine kinases are involved in this process. A recent study now implicates the other two ErbB family members, ErbB-3 and -4. Exposure of ER+ breast cancer cells to the pure antiestrogen, fulvestrant, increased levels of ErbB-3 or ErbB-4 and sensitivity to the growth-stimulatory effects of heregulin β1, a potent ligand for these receptors. Thus, the initial growth-inhibitory effects of fulvestrant appear compromised by cellular plasticity that allows rapid compensatory growth stimulation via ErbB-3/4. Further evaluation of pan-ErbB receptor inhibitors in endocrine-resistant disease appears warranted.
Low-Cost CPW Meander Inductors Utilizing Ink-Jet Printing on Flexible Substrate for High-Frequency Applications (2013)

This paper describes the design and fabrication of low-cost coplanar waveguide (CPW) miniature meander inductors. Inductors are fabricated on a flexible plastic polyimide foil in ink-jet printed technology with silver nanoparticle ink in a single layer. For the first time, the detailed characterization and simulation of CPW inductors in this technology is reported. The inductors are developed with impressive measured self-resonance frequency up to 18.6 GHz. The 2.107-nH inductor measures only 1 mm × 1.7 mm × 0.075 mm and demonstrates a high level of miniaturization in ink-jet printing technology. The measured response characteristics are in excellent agreement with the predicted simulation response.
3D Video and Free Viewpoint Video - Technologies, Applications and MPEG Standards (2006)

An overview of 3D and free viewpoint video is given in this paper with special focus on related standardization activities in MPEG. Free viewpoint video allows the user to freely navigate within real world visual scenes, as known from virtual worlds in computer graphics. Examples are shown, highlighting standards conform realization using MPEG-4. Then the principles of 3D video are introduced providing the user with a 3D depth impression of the observed scene. Example systems are described again focusing on their realization based on MPEG-4. Finally multi-view video coding is described as a key component for 3D and free viewpoint video systems. The conclusion is that the necessary technology including standard media formats for 3D and free viewpoint is available or will be available in the near future, and that there is a clear demand from industry and user side for such applications. 3D TV at home and free viewpoint video on DVD will be available soon, and will create huge new markets
Optimization and Scale-up of a Pd-Catalyzed Aromatic C−N Bond Formation: A Key Step in the Synthesis of a Novel 5-HT1B Receptor Antagonist (2008)

Searching for the best synthetic route for a given target molecule is a complex task and, by the same token, a key deliverable from a process R&D department. In this vein the challenge for our group was to identify a sustainable manufacturing process for a chiral compound, AR-A2, to be developed for the treatment of certain neurological disorders. Besides designing a method for assembling the core (R)-2-aminotetralin nucleus, a key feature in the overall synthesis was to provide a robust procedure for creating a new C−N bond between an aromatic ring and a heterocyclic moiety. The methodology employed a Buchwald−Hartwig coupling, and a highly efficient catalytic process was developed using Pd(OAc)2 as precatalyst, with loadings as low as 0.47 mol % (in laboratory trials one order of magnitude lower) together with (R)-BINAP as ligand. Optimizing the reaction conditions allowed a virtually quantitative conversion of the brominated aromatic substrate after heating to 110−115 °C in toluene for 4 h. Telescoping this step with a succeeding catalytic hydrogenation to effect an N-debenzylation, followed by precipitation of the benzoate salt offered an overall yield for the two consecutive steps of 88% at 125-kg batch size, combined with excellent stereochemical product purity of 98% ee.
Receptor-mediated endocytosis (1985)

Research Article| November 15 1985 Receptor-mediated endocytosis T Wileman; T Wileman Search for other works by this author on: This Site PubMed Google Scholar C Harding; C Harding Search for other works by this author on: This Site PubMed Google Scholar P Stahl P Stahl Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1985) 232 (1): 1–14. https://doi.org/10.1042/bj2320001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation T Wileman, C Harding, P Stahl; Receptor-mediated endocytosis. Biochem J 15 November 1985; 232 (1): 1–14. doi: https://doi.org/10.1042/bj2320001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1985 London: The Biochemical Society1985 Article PDF first page preview Close Modal You do not currently have access to this content.
T-Lymphocyte Priming and Protection Against Friend Leukemia by Vaccinia-Retrovirus env Gene Recombinant (1986)

The current prevalence of the acquired immune deficiency syndrome in humans has provoked renewed interest in methods of protective immunization against retrovirus-induced diseases. In this study, a vaccinia-retrovirus recombinant vector was constructed to study mechanisms of immune protection against Friend virus leukemia in mice. The envelope (env) gene from Friend murine leukemia virus (F-MuLV) was inserted into the genome of a vaccinia virus expression vector. Infected cells synthesized gp85, the glycosylated primary product of the env gene. Processing to gp70 and p15E, and cell surface localization, were similar to that occurring in cells infected with F-MuLV. Mice inoculated with live recombinant vaccinia virus had an envelope-specific T-cell proliferative response and, after challenge with Friend virus complex, developed neutralizing antibody and cytotoxic T cells (CTL) and were protected against leukemia. In contrast, unimmunized and control groups developed a delayed neutralizing antibody response, but no detectable CTL, and succumbed to leukemia. Genes of the major histocompatibility complex influenced protection induced by the vaccinia recombinant but not that induced by attenuated N-tropic Friend virus.
Fusing multiple sensors through behaviors with the distributed architecture (2010)

This paper describes a new action selection mechanism that allows the robot controller to dynamically determine which goals (tasks) are most applicable in the current state of the environment. This allows the robotic controller to resolve conflicting goals that arise, allow multiple non-conflicting goals to run simultaneously, and dynamically switch to a new goal if the target for the goal has been found in the environment. This is accomplished by using a behavior based paradigm and allowing each behavior to calculate its own activation level (run level). The behaviors then use the activation level to compete for control in a new distributed control architecture to allow execution of multiple (and sometimes conflicting) goals on a robotic system.
Optical bleaching of perovskite (CH3NH3)PbI3 through room-temperature phase transformation induced by ammonia (2014)

Ammonia induces a phase transformation of perovskite (CH3NH3)PbI3, leading to a rapid (<1 s) change in its color from brown to colorless (400-800 nm). This color change is reversed within seconds upon removing the NH3 source.
Reactive Oxygen Species in Inflammation and Tissue Injury (2013)

Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.
[The effect of phospholipid liposomes on atherosclerosis and serum lipid in rabbits]. (1996)

In order to study the effect of oral phospholipid liposomes on regression of atherosclerosis process, serum total cholesterol triglyceride, lipoprotein cholesterol and atherosclerotic lesion on the aorta wall in different groups of 20 New Zealand rabbits were observed. Results showed that phospholipid liposomes could obviously increase high density lipoprorein cholesterol concentration and decrease serum total cholesterol triglyceride and very low density lipoprorein cholesterol concentration. Phospholipid liposomes could also reduce the size of atherosclerotic lesion on the aortic wall. In comparision with the results observed in phospholipid group, there was significant difference (P < 0.05, P < 0.01 or P < 0.001). It suggested that oral phospholipid liposomes could effectively regress atherosclerotic lesion on the arterial wall and regulate serum lipid to reduce cholesterol deposit on the arterial wall in experimental rabbits. It might provide some experimental basis for human being to prevent and treat atherosclerosis.
Deficiency of protein C in congenital thrombotic disease. (1981)

A family with a history of recurring thrombosis was studied to determine if a plasma protein deficiency could account for the observed disease. Protein C levels in plasma were determined immunologically using the Laurell rocket technique. The propositus, his father, and his paternal uncle, who are severely affected, had 38-49% of normal levels of protein C antigen, whereas unaffected family members had normal levels. There was no familial deficiency of antithrombin III and plasminogen. Because activated protein C is a potent in vitro anticoagulant enzyme and an in vivo profibrinolytic agent, it is suggested that the recurrent thrombotic disease in this family is due to an inherited deficiency in protein C.
Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells (2014)

Hemophilia A is the X-linked bleeding disorder caused by deficiency of coagulation factor VIII (FVIII). To address serious complications of inhibitory antibody formation in current replacement therapy, we created tobacco transplastomic lines expressing FVIII antigens, heavy chain (HC) and C2, fused with the transmucosal carrier, cholera toxin B subunit. Cholera toxin B-HC and cholera toxin B-C2 fusion proteins expressed up to 80 or 370 µg/g in fresh leaves, assembled into pentameric forms, and bound to GM1 receptors. Protection of FVIII antigen through bioencapsulation in plant cells and oral delivery to the gut immune system was confirmed by immunostaining. Feeding of HC/C2 mixture substantially suppressed T helper cell responses and inhibitor formation against FVIII in mice of 2 different strain backgrounds with hemophilia A. Prolonged oral delivery was required to control inhibitor formation long-term. Substantial reduction of inhibitor titers in preimmune mice demonstrated that the protocol could also reverse inhibitor formation. Gene expression and flow cytometry analyses showed upregulation of immune suppressive cytokines (transforming growth factor β and interleukin 10). Adoptive transfer experiments confirmed an active suppression mechanism and revealed induction of CD4(+)CD25(+) and CD4(+)CD25(-) T cells that potently suppressed anti-FVIII formation. In sum, these data support plant cell-based oral tolerance for suppression of inhibitor formation against FVIII.
Oxidized low-density lipoprotein, OXPAPC, corrects defects in maturation and cytokine secretion of peripheral blood dendritic cells from sepsis patients. (2014)

DCs from sepsis patients are defective in maturation and cytokine secretion and these defects can be corrected by OXPAPC treatment.
Inhibitors of c-Jun N-Terminal Kinases: An Update (2014)

The c-Jun N-terminal kinases (JNKs) are serine/threonine kinases implicated in the pathogenesis of various diseases. Recent advances in the development of novel inhibitors of JNKs will be reviewed. Significant progress in the design of JNK inhibitors displaying selectivity versus other kinases has been achieved within the past 4 years. However, the development of isoform selective JNK inhibitors is still an open task.
Effect of trifluoroethanol on protein secondary structure: an NMR and CD study using a synthetic actin peptide (1992)

The structure of a synthetic peptide comprising the 28 amino-terminal residues of actin has been examined by 1H-NMR and CD spectroscopy. The peptide is largely unstructured and flexible in solution but becomes increasingly structured at higher trifluoroethanol (TFE) concentrations. As judged by CD with the use of two additional peptides (actin 1-20 and actin 18-28), TFE induces formation of up to 48% helical content within residues 1-20, while residues 21-28 exhibit no helical propensity. Similar results were obtained by using NMR-derived distance information in restrained molecular dynamics calculations. The calculated structure of actin 1-28 peptide in 80% TFE is well defined for the first 23 residues with a backbone root mean square deviation of 0.5 A. Two helices are formed from residues 4-13 and 16-20, and a beta-turn is formed from residues 13-16. The N-terminal residues 1-3 exhibit increased flexibility and a helix-like conformation while the C-terminal residues 21-28 show no regular secondary structure. These results are compared with the predicted secondary structure and the structure of the corresponding sequence in the crystal structure of actin [Kabsch et al. (1990) Nature 347, 37-44]. The significance of the TFE-induced peptide structure is discussed.