gebhart/patrepeval huggingface dataset:
Highly Purified Recombinant Adeno-Associated Virus Vectors Are Biologically Active and Free of Detectable Helper and Wild-Type Viruses (1999)

Gene transfer vectors based on the replication-defective human parvovirus, adeno-associated virus type 2 (AAV-2), are viable candidates for in vivo and ex vivo human use. However, widespread testing of AAV vectors has been limited by difficulties in generating pure, high-titer vector stocks that are fully characterized. To address these issues, we have developed a single-step purification scheme using heparin affinity chromatography. Recovery from the crude lysate starting material exceeds 70%, and the end product rAAV vector is highly purified and appears to be free of adenovirus and cellular contaminates. Importantly, purified vectors retain predicted in vivo biologic activity. Concurrently, we have developed simple and rapid approaches for vector quantification using real-time PCR. These new methods, combined with the use of stable producer cell lines for rAAV production, make the commercial production of rAAV vectors for human use truly viable and pragmatic.
Method for avoiding false-positive results occurring in immunoglobulin M enzyme-linked immunosorbent assays due to presence of both rheumatoid factor and antinuclear antibodies (1981)

In a double-sandwich immunoglobulin M (IgM) enzyme-linked immunosorbent assay recently developed for the detection of IgM antibodies to Toxoplasma, the presence of either rheumatoid factor or antinuclear antibodies did not cause false-positive results. We recently noted, however, that in certain sera containing both rheumatoid factor and antinuclear antibodies, false-positive results do occur. In experiments to define the nature of the cross-reaction, these false-positive results were not found to be a consequence of interactions of the sera with Toxoplasma antigens, but rather were due to interactions of rheumatoid factor-antinuclear antibodies with the Fc portion of IgG antibodies used for the enzyme conjugate. This was avoided when the F(ab')2 fragment of IgG was used for the conjugate. The use of such F(ab')2 conjugates did not affect the sensitivity and, thereby, the usefulness of the double-sandwich IgM enzyme-linked immunosorbent assay for the diagnosis of acute acquired or congenital Toxoplasma infections. We concluded that F(ab')2 fragments of IgG antibodies can be used as enzyme conjugates to avoid false-positive results in sera positive for both rheumatoid factor and antinuclear antibodies in either the conventional test or in our double-sandwich IgM enzyme-linked immunosorbent assay.
Role ofBacillus anthracis Spore Structures in Macrophage Cytokine Responses (2007)

The innate immune response of macrophages (Mphi) to spores, the environmentally acquired form of Bacillus anthracis, is poorly characterized. We therefore examined the early Mphi cytokine response to B. anthracis spores, before germination. Mphi were exposed to bacilli and spores of Sterne strain 34F2 and its congenic nongerminating mutant (DeltagerH), and cytokine expression was measured by real-time PCR and an enzyme-linked immunosorbent assay. The exosporium spore layer was retained (exo+) or removed by sonication (exo-). Spores consistently induced a strong cytokine response, with the exo- spores eliciting a two- to threefold-higher response than exo+ spores. The threshold for interleukin-1beta (IL-1beta) production by wild-type Mphi was significantly lower than that required for tumor necrosis factor alpha expression. Cytokine production was largely dependent on MyD88, suggesting Toll-like receptor involvement; however, the expression of beta interferon in MyD88-/- Mphi suggests involvement of a MyD88-independent pathway. We conclude that (i) the B. anthracis spore is not immunologically inert, (ii) the exosporium masks epitopes recognized by the Mphi, (iii) the Mphi cytokine response to B. anthracis involves multiple pattern recognition receptors and signaling pathways, and (iv) compared to other cytokines, IL-1beta is expressed at a lower spore concentration.
Rho Family GTPases and Neuronal Growth Cone Remodelling: Relationship between Increased Complexity Induced by Cdc42Hs, Rac1, and Acetylcholine and Collapse Induced by RhoA and Lysophosphatidic Acid (1997)

Rho family GTPases have been assigned important roles in the formation of actin-based morphologies in nonneuronal cells. Here we show that microinjection of Cdc42Hs and Rac1 promoted formation of filopodia and lamellipodia in N1E-115 neuroblastoma growth cones and along neurites. These actin-containing structures were also induced by injection of Clostridium botulinum C3 exoenzyme, which abolishes RhoA-mediated functions such as neurite retraction. The C3 response was inhibited by coinjection with the dominant negative mutant Cdc42Hs(T17N), while the Cdc42Hs response could be competed by coinjection with RhoA. We also demonstrate that the neurotransmitter acetylcholine (ACh) can induce filopodia and lamellipodia on neuroblastoma growth cones via muscarinic ACh receptor activation, but only when applied in a concentration gradient. ACh-induced formation of filopodia and lamellipodia was inhibited by preinjection with the dominant negative mutants Cdc42Hs(T17N) and Rac1(T17N), respectively. Lysophosphatidic acid (LPA)-induced neurite retraction, which is mediated by RhoA, was inhibited by ACh, while C3 exoenzyme-mediated neurite outgrowth was inhibited by injection with Cdc42Hs(T17N) or Rac1(T17N). Together these results suggest that there is competition between the ACh- and LPA-induced morphological pathways mediated by Cdc42Hs and/or Rac1 and by RhoA, leading to either neurite development or collapse.
SOLIDS RETENTION IN ANAEROBIC WASTE TREATMENT SYSTEMS (1970)

Fifty years have passed since the first application of separate sludge di gestion to waste treatment. During this period numerous reports have con tributed to the knowledge of anaerobic waste treatment systems. In recent years, primarily since 1960, more re search attention has been directed to ward the microbial population dy namics of anaerobic systems (1) (2) (3). This paper presents the results of a laboratory study into the biolog ical solids retention time aspects of anaerobic waste treatment.
Plasma erythropoietin in health and disease. (1980)

Erythropoietin is a hormone produced by the kidneys and by certain extrarenal tissues and released into the circulation in response to tissue hypoxia. Its study has provided new information about oxygen transport and bone marrow stem cell function and its determination in plasma can give valuable diagnostic clues as to the etiology and pathogenesis of anemias and polycythemias. The various methods used for such measurements are discussed, and it is recommended that the in vivo bioassay in polycythemic mice be utilized until a workable radioimmune assay has been perfected. The results with the use of this in vivo bioassay to measure plasma erythropoietin in patients with uncomplicated anemia, aplastic anemia, anemia of renal disease, anemia of chronic inflammatory or neoplastic disorder polycythemia vera, and secondary polycythemia are charted and their diagnostic significance discussed.
Genetic Association of Bovine Lymphocyte Antigen DRB3 Alleles with Immunological Traits of Holstein Cattle (1997)

The associations between alleles at the BoLA (bovine lymphocyte antigen) DRB3 locus and 20 indicator traits of innate and adaptive immunity were investigated. Periparturient Holsteins (n = 127) were genotyped at the BoLA DRB3 locus using polymerase chain reaction and restriction fragment length polymorphism. Twenty-two alleles were observed in the study population, and frequencies ranged from 21 to < 1%. The same cattle were tested for a total of 20 innate and adaptive immunity traits, including lymphocyte response to mitogens (proliferative responses and Ig secretion), serum Ig, complement and conglutinin concentrations, total leukocyte count, and selected assays for neutrophil function. Models with gene substitution effects were used to investigate associations between BoLA DRB3 alleles and each of the immunological variables. Significant associations were found with 13 of the leukocyte functions tested. The number of immune parameters with significant associations with any allele ranged from 0 (with alleles DRB3.2*23 and DRB3.2*27) to 7 (with DRB3.2*8). The immunological parameter that had the most associations with alleles was serum IgG2 concentration with 6 alleles. One group of 4 alleles (representing 46% of the total allele frequency) was uniformly associated with increased IgM and complement and decreased mononuclear cell numbers. Thus, we demonstrated that the BoLA DRB3 genotype can influence measures of innate and adaptive immunity.
Reassembled plasma low density lipoproteins. Phospholipid-cholesterol ester-apoprotein B complexes. (1984)

Reassembled low density lipoprotein (LDL) complexes have been prepared by the interaction of lipid-free sodium deoxycholate-solubilized apoprotein B (apoB) of native human LDL with preformed, 200 A in diameter, microemulsions of cholesteryl oleate (CO), surface-stabilized by either egg yolk phosphatidylcholine ( EYPC ) or dimyristoyl phosphatidylcholine (DMPC). Gel chromatography of PC/CO/apoB complexes shows co-elution of the complex at 43% PC, 43% CO, and 14% apoB. Negative stain electron microscopy shows the particles to be circular, homogeneous, and approximately 200 A in diameter. PC/CO/apoB complexes exhibit beta-migration on agarose gels and show one high molecular weight protein band on 3.0% sodium dodecyl sulfate-polyacrylamide gels. Differential scanning calorimetry and x-ray scattering show the lipids in the complexes to undergo at least two specific thermal transitions depending on lipid composition, one associated with the core-located cholesterol esters similar to LDL and the protein-free microemulsions and the other from the phospholipid forming the surface monolayer. In addition, particle disruption-protein unfolding/denaturation occur irreversibly at 80-85 degrees C. At 4 degrees C, the secondary structure of apoB on complexes of EYPC /CO/apoB is similar to that of native LDL. For complexes of DMPC/CO/apoB, the secondary structure shows less alpha-helix which correlates with the difference in surface lipid environment. The reassembled complexes of PC/CO/apoB provide a defined system in which the components may be varied systematically in order to study the molecular organization, molecular interactions, and metabolism of LDL.
Imaging selective vulnerability in the developing nervous system (2010)

Why do cells in the central nervous system respond differently to different stressors and why is this response so age-dependent? In the immature brain, there are regions of selective vulnerability that are predictable and depend on the age when the insult occurs and the severity of the insult. This damage is both region and cell population specific. Vulnerable cell populations include the subplate neurons and oligodendrocyte precursors early in development and the neurons closer to the end of human gestation. Mechanisms of injury include excitotoxicity, oxidative stress and inflammation as well as accelerated apoptosis. Advanced imaging techniques have shown us particular patterns of injury according to age at insult. These changes seen in the newborn at the time of injury on magnetic resonance imaging correlate well with the neurodevelopmental outcome. New questions about how the injury evolves and how the newborn brain adapts and repairs itself have emerged as we now know that injury in the newborn brain can evolve over days and weeks, rather than hours. The ability to follow these processes has allowed us to investigate the role of repair in attenuating the injury. Neurogenesis and angiogenesis exist in response to ischemic injury and can be enhanced by processes that are known to protect the brain. The injury response in the developing brain is a complex process that evolves over time and is amenable to repair.
Natural and synthetic sialic acid‐containing inhibitors of influenza virus receptor binding (2003)

Influenza viruses attach to susceptible cells via multivalent interactions of their haemagglutinins with sialyloligosaccharide moieties of cellular glycoconjugates. Soluble macromolecules containing sialic acid from animal sera and mucosal fluids can act as decoy receptors and competitively inhibit virus-mediated haemagglutination and infection. Although a role for these natural inhibitors in the innate anti-influenza immunity is still not clear, studies are in progress on the design of synthetic sialic acid-containing inhibitors of receptor binding which could be used as anti-influenza drugs.
Correlation between In Vivo and In Vitro Efficacy of Antimicrobial Agents against Foreign Body Infections (1990)

Implant-associated infections are often resistant to antibiotic therapy. Routine sensitivity tests fail to predict therapeutic success. Therefore experimental in vitro tests were sought that would better correlate with drug efficacy in device-related infections. The activity of six different antibiotics against methicillin-resistant Staphylococcus epidermidis was investigated. In vivo studies were performed with the guinea pig tissue-cage animal model; in vitro studies with minimum inhibiting and bactericidal concentrations, time-kill studies of growing and stationary-phase microorganisms, the killing of glass-adherent S. epidermidis. Drug efficacy on stationary and adherent microorganisms, but not minimum inhibiting concentrations, predicted the outcome of device-related infections. Rifampin cured 12 of 12 infections and was also the most efficient drug in any experimental in vitro test. Similarly, the failure of ciprofloxacin to eradicate foreign body infections correlated with its low efficacy on stationary-phase and adherent S. epidermidis.
Fibroblast-Specific Deletion of Hypoxia Inducible Factor-1 Critically Impairs Murine Cutaneous Neovascularization and Wound Healing (2015)

Background: Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. Methods: The authors generated floxed HIF-1 mice (HIF-1loxP/loxP) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1loxP/loxP with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. Results: Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p < 0.05). HIF-1α knockout mice showed significantly impaired revascularization of ischemic tissue and wound closure and vascularity (p < 0.05). Conclusions: Loss of HIF-1α from fibroblasts results in delayed wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.
How is visual salience computed in the brain? Insights from behaviour, neurobiology and modelling (2017)

Inherent in visual scene analysis is a bottleneck associated with the need to sequentially sample locations with foveating eye movements. The concept of a 'saliency map' topographically encoding stimulus conspicuity over the visual scene has proven to be an efficient predictor of eye movements. Our work reviews insights into the neurobiological implementation of visual salience computation. We start by summarizing the role that different visual brain areas play in salience computation, whether at the level of feature analysis for bottom-up salience or at the level of goal-directed priority maps for output behaviour. We then delve into how a subcortical structure, the superior colliculus (SC), participates in salience computation. The SC represents a visual saliency map via a centre-surround inhibition mechanism in the superficial layers, which feeds into priority selection mechanisms in the deeper layers, thereby affecting saccadic and microsaccadic eye movements. Lateral interactions in the local SC circuit are particularly important for controlling active populations of neurons. This, in turn, might help explain long-range effects, such as those of peripheral cues on tiny microsaccades. Finally, we show how a combination of in vitro neurophysiology and large-scale computational modelling is able to clarify how salience computation is implemented in the local circuit of the SC.This article is part of the themed issue 'Auditory and visual scene analysis'.
Laparoscopic skills training and assessment (2004)

The tools are now available for the development of a structured, competency-based, laparoscopic surgical training programme.
Thiordoxin regulates the DNA binding activity of NF-χB by reduction of a disulphid bond involving cysteine 62 (1992)

A role for redox regulation in activation of the NF-kappa B transcription factor was suggested by the observation that DNA binding activity of free protein, but not preformed DNA-protein complex, is inhibited by -SH modifying agents but enhanced by reducing agents. Mutagenesis of conserved cysteine residues in the p50 subunit identified amino acid 62 as being important for DNA binding, as a serine substitution at this position reduces DNA binding affinity, but renders the protein insensitive to -SH modifying agents. DNA binding activity of the wild type protein but not the amino acid 62 mutant was also stimulated by thioredoxin while detection of disulphide cross linked dimers in p50 but not the amino acid 62 mutant suggests that thioredoxin stimulates DNA binding by reduction of a disulphide bond involving cysteine 62. The physiological relevance of these findings was supported by the observation that cotransfection of a plasmid expressing human thioredoxin and an HIV LTR driven reporter construct resulted in an NF-kappa B dependent increase in expression of the reporter gene. Thus modification of p50 by thioredoxin, a gene induced by stimulation of T-lymphocytes in parallel with NF-kappa B translocation, is a likely step in the cascade of events leading to full NF-kappa B activation.
TH-17 Cell-Related Cytokines' Potential Role in the Pathogenesis of Severe Asthma (2008)

Severe asthma represents a distinct, poorly-understood phenotype of asthma that has higher morbidity, mortality and a disproportionate need for health care support. Studies have indicated the presence of a specific inflammatory response in severe asthmatics, including the paucity of expression of classical Th-2 type cytokines. Following antigenic stimulation, naive CD4+ T cells proliferate and differentiate into various effector subsets such as Th-1 and Th-2 cells. A third subset of CD4+ T cells has recently been identified and designated as Th-17 cells, which produce IL-17A and F, IL-6, and TNF-alpha. In severe asthma, there may be a predominant Th-17 phenotype. These cells may promote the release of neutrophil chemotactic factors and induce the expression of GR-beta, which is responsible for corticosteroid hyporesponsiveness in immune and structural cells. If the role of Th-17 cytokines is confirmed, it might provide a new option in controlling this refractory subtype of asthma.
A Study of Reaction Kinetics by Near-Infrared Spectroscopy. 1. Comprehensive Analysis of a Model Epoxy/Amine System (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Study of Reaction Kinetics by Near-Infrared Spectroscopy. 1. Comprehensive Analysis of a Model Epoxy/Amine SystemJovan Mijovic and Sasa AndjelicCite this: Macromolecules 1995, 28, 8, 2787–2796Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ma00112a026https://doi.org/10.1021/ma00112a026research-articleACS PublicationsRequest reuse permissionsArticle Views1944Altmetric-Citations154LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Efficient JavaVM just-in-time compilation (1998)

Conventional compilers are designed for producing highly optimized code without paying much attention to compile time. The design goals of Java just-in-time compilers are different: produce fast code at the smallest possible compile time. In this article we present a very fast algorithm for translating JavaVM byte code to high quality machine code for RISC processors. This algorithm handles combines instructions, does copy elimination and coalescing and does register allocation. It comprises three passes: basic block determination, stack analysis and register preallocation, final register allocation and machine code generation. This algorithm replaces an older one in the CACAO JavaVM implementation reducing the compile time by a factor of seven and producing slightly faster machine code. The speedup comes mainly from following simplifications: fixed assignment of registers at basic block boundaries, simple register allocator better exception handling better memory management and fine tuning the implementation. The CACAO system is currently faster than every JavaVM implementation for the Alpha processor and generates machine code for all used methods of the javac compiler and its libraries in 60 milliseconds on an Alpha workstation.