gebhart/patrepeval huggingface dataset:
Evaluation of new generationSalmonella entericaserovar Typhimurium vaccines with regulated delayed attenuation to induce immune responses against PspA (2008)

Increasing the immunogenicity to delivered antigens by recombinant attenuated Salmonella vaccines (RASV) has been the subject of intensive study. With this goal in mind, we have designed and constructed a new generation of RASV that exhibit regulated delayed attenuation. These vaccine strains are phenotypically wild type at the time of immunization and become attenuated after colonization of host tissues. The vaccine strains are grown under conditions that allow expression of genes required for optimal invasion and colonization of host tissues. Once established in the host, these virulence genes are turned off, fully attenuating the vaccine strain. In this study, we compared 2 of our newly developed regulated delayed attenuation Salmonella enterica serovar Typhimurium strains chi9088 and chi9558 with the Deltacya Deltacrp Deltaasd strain chi8133, for their abilities to express and present a secreted form of the alpha-helical region of pneumococcal surface protein A (PspA) to the mouse immune system. All 3 strains induced high levels of serum antibodies specific for PspA as well as to Salmonella antigens in orally immunized mice. However, both RASVs expressing delayed attenuation elicited significantly greater anti-PspA immune responses, including serum IgG and T cell secretion of IL-4 and IFN-gamma, than other groups. Also, vaccination with delayed attenuation strains resulted in a greater degree of protection against Streptococcus pneumoniae challenge than in mice vaccinated with chi8133 (71-86% vs. 21% survival, P </= 0.006). Together, the results demonstrate that the regulated attenuation strategy results in highly immunogenic antigen delivery vectors for oral vaccination.
Paper‐PEG‐based membranes for hydrophobic interaction chromatography: Purification of monoclonal antibody (2007)

This article discusses the preparation of novel Paper-PEG interpenetrating polymer network-based membranes as inexpensive alternative to currently available adsorptive membranes. The Paper-PEG membranes were developed for carrying out hydrophobic interaction membrane chromatography (HIMC). PEG is normally very hydrophilic but can undergo phase separation and become hydrophobic in the presence of high antichaotropic salt concentrations. Two variants of the Paper-PEG membranes, Paper-PEG 1 and Paper-PEG 2 were prepared by grafting different amounts of the polymer on filter paper and these were tested for their hydraulic properties and antibody binding capacity. The better of the two membranes (Paper-PEG 1) was then used for purifying the monoclonal antibody hIgG1-CD4 from simulated mammalian cell culture supernatant. The processing conditions required for purification were systematically optimized. The dynamic antibody binding capacity of the Paper-PEG 1 membrane was about 9 mg/mL of bed volume. A single step membrane chromatographic process using Paper-PEG 1 membrane gave high monoclonal antibody purity and recovery. The hydraulic permeability of the paper-based membrane was high and was maintained even after many runs, indicating that membrane fouling was negligible and the membrane was largely incompressible.
Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors (2004)

Stimulation of cells with various peptide growth factors induces the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) through activation of phosphatidylinositol 3-kinase. The action of this enzyme is reversed by that of the tumor suppressor PTEN. With the use of cells overexpressing NADPH oxidase 1 or peroxiredoxin II, we have now shown that H2O2 produced in response to stimulation of cells with epidermal growth factor or platelet-derived growth factor potentiates PIP3 generation and activation of the protein kinase Akt induced by these growth factors. We also show that a small fraction of PTEN molecules is transiently inactivated as a result of oxidation of the essential cysteine residue of this phosphatase in various cell types stimulated with epidermal growth factor, platelet-derived growth factor, or insulin. These results suggest that the activation of phosphatidylinositol 3-kinase by growth factors might not be sufficient to induce the accumulation of PIP3 because of the opposing activity of PTEN and that the concomitant local inactivation of PTEN by H2O2 might be needed to increase the concentration of PIP3 sufficiently to trigger downstream signaling events. Furthermore, together with previous observations, our data indicate that peroxiredoxin likely participates in PIP3 signaling by modulating the local concentration of H2O2.
Production of Short-Chain-Length/Medium-Chain-Length Polyhydroxyalkanoate (PHA) Copolymer in the Plastid of Arabidopsis thaliana Using an Engineered 3-Ketoacyl-acyl Carrier Protein Synthase III (2009)

Short-chain-length/medium-chain-length (SCL/MCL) polyhydroxyalkanoate (PHA) was produced in the plastids of Arabidopsis thaliana. Phe87Thr (F87T) mutated 3-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) from Escherichia coli , and Ser325Thr/Gln481Lys (ST/QK) mutated polyhydroxyalkanoate (PHA) synthase (PhaC1) from Pseudomonas sp. 61-3, along with the beta-ketothiolase (PhaA) and acetoacetyl-CoA reductase (PhaB) from Ralstonia eutropha (Cupriavidus necator) genes were introduced into Arabidopsis. The transgenic Arabidopsis produced PHA copolymers composed of monomers consisting of 4-14 carbons. The introduction of the engineered PHA synthase resulted in a 10-fold increase in PHA content compared to plants expressing the wild-type PHA synthase. In addition, expression of the engineered fabH gene in the plastid led to an increase in the amount of the SCL monomer, 3-hydroxybutyrate, incorporated into PHA, and contributed to supply of MCL monomers for PHA production.
A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow (2004)

Abstract Homing of bone marrow stromal cells (MSCs) to bone and bone marrow after transplantation, important for the correction of conditions such as metabolic storage disorders, can occur but with poor efficiency. Substantial improvements in engraftment will be required in order to derive a clinical benefit from MSC transplantation. Chemokines are the most important factors controlling cellular migration. Stromal-derived factor-1 (SDF-1) has been shown to be critical in promoting the migration of cells to the bone marrow, via its specific receptor CXCR4. The aim of our study was to investigate CXCR4 expression on MSCs and its role in mediating migration to bone marrow. We show that CXCR4, although present at the surface of a small subset of MSCs, is important for mediating specific migration of these cells to bone marrow. (Blood. 2004; 104:2643-2645)
Human stem cell-derived retinal cells for macular diseases (2014)

1 report the mid-term and long-term outcomes of the use of human embryonic stem-cell (hESC)-derived retinal pigment epithelial cells for the treatment of dry atrophic age-related macular degeneration and Stargardt's macular dystrophy, the leading causes of adult and juvenile blindness in the developed world. Both eye diseases involve a disruption of the retinal pigment epithelium, a layer of cells behind the retina that helps to maintain photoreceptors and preserve the blood-retina barrier. In the studies, hESC were diff erentiated into retinal pigment epithelium cells, and these cells were injected into the subretinal space in the eye with the worst vision in 18 patients— nine with atrophic age-related macular degeneration and nine with Stargardt's macular dystrophy. The median follow-up was 22 months. Visual acuity improved in ten eyes, remained the same or improved in seven eyes, and decreased by more than ten letters in one eye. The untreated fellow eyes did not show similar improvement. The safety and visual acuity outcomes in the 18 patients further validate the earlier fi ndings reported for the fi rst patient in two studies in 2012. 2,3
Enhancements for integrated wireless personal communications over metropolitan area networks (2002)

The IEEE 802.6 metropolitan area network (MAN) has been proposed previously to provide for the distributed control of networks providing personal communications services (PCS). This paper continues investigations into voice transport on the MAN using pre-arbitrated (PA) bandwidth, and for signaling and data transport using queue arbitrated (QA) bandwidth. A new scheme for the transport of PCS voice is proposed. Capacity gains are realized with PA access by locating a gateway to the public switched telephone network (PSTN) at the head of bus (HOB) in a closed-bus MAN. Reductions in PCS signaling delays on the MAN are realized by applying the preemptive priority mechanism (PPM). In summary, improvements to the PA and QA transport mechanisms, as applied to personal communications networks (PCNs), are developed and assessed. Additionally, an architecture for a MAN-based PCN is presented in the context of the intelligent network (IN) and future migration towards ATM/B-ISDN.
Clinical Applications of VEGF-Trap (Aflibercept) in Cancer Treatment (2010)

Angiogenesis is one of the key acquired characteristics or "hallmarks" essential for the growth and development of all solid tumor types. The antiangiogenic agent vascular endothelial growth factor-Trap (VEGF-Trap) (aflibercept), which is a composite decoy receptor based on VEGF receptor-1 and VEGF receptor-2 fused to an Fc segment of immunoglobulin G1 that binds specifically to VEGF, has demonstrated preclinical efficacy in a range of different tumor types. VEGF-Trap exerts its antiangiogenic effects through regression of tumor vasculature, remolding or normalization of surviving vasculature, and inhibition of new tumor vessel growth. Preclinical and clinical studies have reported that VEGF-Trap can be combined effectively with both chemotherapy and radiotherapy. This review examines the main effects of VEGF-Trap on tumor vasculature and on different types of solid tumors, and explores the preclinical and clinical benefits of incorporating VEGF-Trap into anticancer treatment strategies.
Maintenance of broad-host-range incompatibility group P and group Q plasmids and transposition of Tn5 in Bartonella henselae following conjugal plasmid transfer from Escherichia coli (1997)

The first demonstration of conjugal plasmid transfer from Escherichia coli to Bartonella henselae is reported. Transconjugants bearing plasmids of incompatibility groups P (IncP) and Q (IncQ), expressing various resistance markers, were generated. Tn5 transposons delivered on suicide plasmids by conjugation showed transpositional insertion into random chromosomal sites.
Dietary Gangliosides Enhance in Vitro Lipid Uptake in Weanling Rats (2005)

We speculate that the enhanced uptake of long-chain fatty acids in weanling rats fed GANG may be caused by a modification in physical properties of the BBM.
UNDERSTANDING ONLINE KNOWLEDGE CONTRIBUTION IN SOCIAL LEARNING PERSPECTIVE (2012)

Online open knowledge sharing is the idea that the Internet can promote the aggregation and dissemination of useful knowledge between a potentially large number of people. Starting from the knowledge sharing idea, various types of online open knowledge sharing services have provided the central platform for users to interact with each other, share their knowledge, and even jointly create new knowledge. In this study, we derive two research questions: 1) what framework can better explain online knowledge contribution? and 2) what factors influence online knowledge contribution? The study draws on both social learning theory and the social model of knowledge creation to investigate the overall antecedents of knowledge contribution and to examine three facets, user-oriented, service-oriented, and community-oriented knowledge contribution behaviour. In the study, we examine which knowledge sharing antecedents motivate people to contribute to knowledge sharing in the framework based on the social model of knowledge creation. We then verify each variable and hypothesis using a survey and the PLS analysis. This study uses social learning perspective to include all three aspects of knowledge sharing behaviour: personal, community-related, and service-related antecedents. With this new perspective, while previous studies have focused on personal cognitive factors in this area, this study examines the integrative influence of factors from social learning and social knowledge creation antecedents. In addition, our findings offer guidance and insights for knowledge sharing service practitioners and managers who are trying to encourage users? contributions.
Quantitative Proteomic Analysis of Niemann-Pick Disease, Type C1 Cerebellum Identifies Protein Biomarkers and Provides Pathological Insight (2012)

Niemann-Pick disease, type C1 (NPC1) is a fatal, neurodegenerative disorder for which there is no definitive therapy. In NPC1, a pathological cascade including neuroinflammation, oxidative stress and neuronal apoptosis likely contribute to the clinical phenotype. While the genetic cause of NPC1 is known, we sought to gain a further understanding into the pathophysiology by identifying differentially expressed proteins in Npc1 mutant mouse cerebella. Using two-dimensional gel electrophoresis and mass spectrometry, 77 differentially expressed proteins were identified in Npc1 mutant mice cerebella compared to controls. These include proteins involved in glucose metabolism, detoxification/oxidative stress and Alzheimer disease-related proteins. Furthermore, members of the fatty acid binding protein family, including FABP3, FABP5 and FABP7, were found to have altered expression in the Npc1 mutant cerebellum relative to control. Translating our findings from the murine model to patients, we confirm altered expression of glutathione s-transferase α, superoxide dismutase, and FABP3 in cerebrospinal fluid of NPC1 patients relative to pediatric controls. A subset of NPC1 patients on miglustat, a glycosphingolipid synthesis inhibitor, showed significantly decreased levels of FABP3 compared to patients not on miglustat therapy. This study provides an initial report of dysregulated proteins in NPC1 which will assist with further investigation of NPC1 pathology and facilitate implementation of therapeutic trials.
GMP-140 binding to neutrophils is inhibited by sulfated glycans. (1991)

GMP-140 is a 140-kDa granule membrane glycoprotein localized to the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells. Expression of GMP-140 on the activated cell surface has been shown to mediate the adhesion of thrombin-activated platelets to neutrophils and monocytes and the transient adhesion of neutrophils to endothelium. In contrast, fluid-phase GMP-140 strongly inhibits the CD18-dependent adhesion of tumor necrosis factor alpha-activated neutrophils to endothelium suggesting that GMP-140 can also serve an anti-adhesive function. In the present report, it is demonstrated that fluid-phase GMP-140 which exists predominantly as a tetramer binds to a single class of high affinity receptor on neutrophils and HL60 cells. Binding of 125I-labeled GMP-140 to neutrophils and HL60 cells and the rosetting of neutrophils and HL60 cells by thrombin-activated platelets were inhibited by EDTA, excess unlabeled fluid-phase GMP-140, Fab fragments of an affinity-purified rabbit anti-GMP-140 antibody, and by the murine anti-GMP-140 monoclonal antibody, AK 4. Both neutrophil and HL60 GMP-140 binding and platelet rosetting were strongly inhibited by heparin, fucoidin, and dextran sulfate 500,000, were partially inhibited by dextran sulfate 5,000 and lambda- and kappa-carrageenan, but were not inhibited by chondroitins 4- and 6-sulfate. Since this sulfated glycan specificity is identical to that previously reported by us for GMP-140, the present results suggest that the sulfated glycan binding site and the neutrophil receptor binding site on GMP-140 are either identical or proximal.
Phosphorylation of Tau Protein as the Link between Oxidative Stress, Mitochondrial Dysfunction, and Connectivity Failure: Implications for Alzheimer’s Disease (2013)

Alzheimer's disease (AD) is defined by the concurrence of abnormal aggregates composed of phosphorylated tau protein and of abnormal cellular changes including neurite degeneration, loss of neurons, and loss of cognitive functions. While a number of mechanisms have been implicated in this complex disease, oxidative stress remains one of the earliest and strongest events related to disease progression. However, the mechanism that links oxidative stress and cognitive decline remains elusive. Here, we propose that phosphorylated tau protein could be playing the role of potential connector and, therefore, that a combined therapy involving antioxidants and check points for synaptic plasticity during early stages of the disease could become a viable therapeutic option for AD treatment.
The production of chaetoglobosins, sterigmatocystin, O-methylsterigmatocystin, and chaetocin by Chaetomium spp. and related fungi (1979)

Production of mycotoxins by Chaetomium spp. and related fungi on rice culture was examined by a combination of cytotoxicity tests using HeLa cells and thin-layer chromatography. Three species, C. mollipilium, C. rectum, and C. subaffine, as well as C. cochliodes and C. globosum, were proved to produce chaetoglobosins. From cultures of four strains of Chaetomium sp., assigned to C. thielavioideum, and one strain of Farrowia sp., chaetocin, sterigmatocystin, and O-methylsterigmatocystin were isolated. Morphological characteristics of the producers of sterigmatocystins are described.
Analysis of resistance to human immunodeficiency virus type 1 protease inhibitors by using matched bacterial expression and proviral infection vectors (1995)

There are already reports, from clinical trials with human immunodeficiency virus type 1 protease inhibitors, of the emergence of drug-resistant mutants which have one or more point mutations in their protease genes. To examine roles of individual and multiple amino acid substitutions in terms of altered enzyme and virus drug sensitivities, we have produced matched vectors for bacterial expression and virus production. Both vectors accept the same restriction enzyme fragment, produced by PCR or PCR-mutagenesis of the protease gene, allowing parallel expression of mutant enzymes in Escherichia coli and in recombinant viruses. The utility of this vector system was demonstrated by using protease variants glycine to valine at amino acid 48 (G48V) and leucine to methionine at amino acid 90 (L90M) identified after passage of HIV-1 in the Roche phase II clinical trial protease inhibitor Ro 31-8959 (H. Jacobsen, K. Yasargil, D. L. Winslow, J. C. Craig, A. Krohn, I. B. Duncan, and J. Mous, Virology 206:527, 1995). G48V, L90M, and G48V/L90M exhibited successively less processing in vitro than the wild-type enzyme, and the purified enzymes were 220-, 20-, and 720-fold, respectively, less sensitive to Ro 31-8959. The reduced enzyme sensitivity correlated directly with the sensitivities of the matched recombinant viruses, in that individual mutations L90M and G48V conferred 2-fold and 4- to 6-fold increases in 50% inhibitory concentration, respectively, whereas G48V/L90M was 8 to 10 times less sensitive to Ro 31-8959. A proviral vector with the entire protease gene deleted was constructed for use as an in vivo recombination target for an overlapping protease PCR fragment, generating wild-type infectious virus. Finally, direct ligation of restriction fragments, generated from random PCR mutagenesis, into the proviral vector should provide a library of protease mutations that allow extremely rapid selection of highly resistant viral variants.
Correction of Murine Sickle Cell Disease Using γ-Globin Lentiviral Vectors to Mediate High-level Expression of Fetal Hemoglobin (2008)

Increased levels of red cell fetal hemogloblin, whether due to hereditary persistence of expression or from induction with hydroxyurea therapy, effectively ameliorate sickle cell disease (SCD). Therefore, we developed erythroid-specific, gamma-globin lentiviral vectors for hematopoietic stem cell (HSC)-targeted gene therapy with the goal of permanently increasing fetal hemoglobin (HbF) production in sickle red cells. We evaluated two different gamma-globin lentiviral vectors for therapeutic efficacy in the BERK sickle cell mouse model. The first vector, V5, contained the gamma-globin gene driven by 3.1 kb of beta-globin regulatory sequences and a 130-bp beta-globin promoter. The second vector, V5m3, was identical except that the gamma-globin 3'-untranslated region (3'-UTR) was replaced with the beta-globin 3'-UTR. Adult erythroid cells have beta-globin mRNA 3'-UTR-binding proteins that enhance beta-globin mRNA stability and we postulated this design might enhance gamma-globin expression. Stem cell gene transfer was efficient and nearly all red cells in transplanted mice expressed human gamma-globin. Both vectors demonstrated efficacy in disease correction, with the V5m3 vector producing a higher level of gamma-globin mRNA which was associated with high-level correction of anemia and secondary organ pathology. These data support the rationale for a gene therapy approach to SCD by permanently enhancing HbF using a gamma-globin lentiviral vector.
Low-Dose Aspirin-Induced Ulceration Is Attenuated by Aspirin–Phosphatidylcholine: A Randomized Clinical Trial (2010)

Low-dose aspirin induced a surprisingly high incidence of acute gastroduodenal ulcers in at risk subjects, highlighting that aspirin's upper GI risk begins early and may require gastroprotection. Local mechanisms of GI protection are important as aspirin's preassociation with surface-active phospholipids significantly reduced mucosal damage. PL2200 may be an attractive alternative or complement to proton pump inhibitors in older patients who are at risk of aspirin-induced ulceration. Longer-term studies assessing clinical GI events are desirable to confirm the clinical GI safety profile of PL2200.
Resonance Properties of Ring Circuits (1957)

The ring guide or ring circuit, a microwave device consisting of a waveguide having the ends connected to form an annular ring, has properties similar to those of ordinary resonant cavities. Wave propagation within the ring guide, its interaction with a waveguide to which it is coupled, and its resonant circuit properties are investigated in this report. The properties of a prototype circuit consisting of a ring guide of rectangular cross section were found to agree with theory.
Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. (1988)

A substantially enriched preparation of Alzheimer paired helical filaments (PHFs) has been used as a starting point for biochemical studies. Pronase treatment, which strips off adhering proteins, leaves a resistant core that is structurally intact. This has been used to raise a monoclonal antibody that decorates the filament core. The antibody has been used to follow the extraction of two peptide fragments (9.5 and 12 kDa) by immunoblotting. The link between the PHF as a morphological entity and these peptides has been established independently by photoaffinity labeling with a chemical ligand to the PHF core. Sequence analysis of these peptides was used to design oligonucleotide probes for cloning a cognate cDNA, which leads to its identification as human microtubule-associated tau protein. The sequencing of the 9.5- and 12-kDa peptides shows they are derived from a conserved region of tau containing three repeating segments. Since these fragments have been copurified with the Pronase-resistant core and are only released by subsequent steps, the corresponding part of the tau molecule must be tightly bound in the PHF core.