gebhart/patrepeval huggingface dataset:
Monoclonal antibodies with specificity for three different serotypes of Marek's disease viruses in chickens. (1983)

A total of 50 antibody-secreting hybridoma cells against Marek's disease virus (MDV) and turkey herpesvirus (HVT) have been produced. Eleven hybridomas were used for serotyping a panel of 15 pathogenic and nonpathogenic strains of MDV and HVT, representing three serotypes. The antibodies from the culture medium have fluorescence antibody (FA) titers of up to 100 and those from mouse ascitic fluid have titers ranging from 10(4) to 10(6). Monoclonal antibody T81 is type-common, i.e., it reacts at equal titer with all MDV and HVT tested. Of the remaining 10 antibodies, eight react only with pathogenic and attenuated strains of MDV (presumably serotype 1), one reacts only with nonpathogenic MDV (presumably) serotype 2), and one reacts only with strains of HVT (presumably serotype 3). Two hybridomas belong to IgG2a and IgG2b subclasses, respectively, and the remaining nine belong to IgG1 subclass. None of the antibodies specific for MDV strains reacted with homologous viruses in serum neutralization (SN), agar gel precipitin (AGP), or membrane immunofluorescence tests. Antibody L78, which is specific for HVT, was reactive with its homologous virus in the SN test; antibody from the culture medium showed an SN titer of 10 and that from mouse ascites a titer of 10,000. None of the antibodies specific for MDV or HVT reacted with other avian or mammalian herpesviruses, avian leukosis viruses (ALV), reticuloendotheliosis viruses (REV), or Marek's disease tumor-associated surface antigen (MATSA) expressed in a lymphoblastoid cell line, MDCC-MSB-1.
Neutral desorption sampling coupled to extractive electrospray ionization mass spectrometry for rapid differentiation of biosamples by metabolomic fingerprinting (2007)

It is of increasing interest and practical importance to develop convenient methods based on mass spectrometry for high-throughput analyses of biological samples. This is usually difficult because of the complex matrix and ion suppression effects. Generation of ions at ambient conditions is a promising solution to these problems because the sample is easily accessible and the ion suppression effect is reduced significantly. A new method for rapid on-line detection of metabolic markers in complex biological samples is described here. It combines atmospheric pressure desorption sampling by a gentle stream of air or nitrogen with extractive electrospray ionization (EESI) and mass spectrometric analysis. The resulting mass spectral fingerprints are shown to be able to detect spoilage of meat even in the frozen (-20 degrees C) state and the contamination of spinach by E. coli, and to identify metabolites and contaminants on human skin within seconds, in an on-line and high-throughput fashion. Typical molecular markers are identified using MS/MS data and by comparison with reference compounds. Differences between closely related samples are easily visualized by using principal component analysis (PCA) of the mass spectra data. The detection limit achieved is 10 fg/cm2 (S/N = 3) for histamine on the surface of frozen meat. The technique reported here shows potential for more advanced applications in multiple disciplines, including food regulation, homeland security, in vivo metabolomics, and clinical diagnosis.
Regulation of gene expression by SPARC during angiogenesis in vitro. Changes in fibronectin, thrombospondin-1, and plasminogen activator inhibitor-1. (1992)

Angiogenesis in vitro, the formation of capillary-like structures by cultured endothelial cells, is associated with changes in the expression of several extracellular matrix proteins. The expression of SPARC, a secreted collagen-binding glycoprotein, has been shown to increase significantly during this process. We now show that addition of purified SPARC protein, or an N-terminal synthetic peptide (SPARC4-23), to strains of bovine aortic endothelial cells undergoing angiogenesis in vitro resulted in a dose-dependent decrease in the synthesis of fibronectin and thrombospondin-1 and an increase in the synthesis of type 1-plasminogen activator inhibitor. SPARC decreased fibronectin mRNA by 75% over 48 h, an effect that was inhibited by anti-SPARC immunoglobulins. Levels of thrombospondin-1 mRNA were diminished by 80%. Over a similar time course, both mRNA and protein levels of type 1-plasminogen activator inhibitor (PAI-1) were enhanced by SPARC and the SPARC4-23 peptide. The effects were dose-dependent with concentrations of SPARC between 1 and 30 micrograms/ml. In contrast, no changes were observed in the levels of either type I collagen mRNA or secreted gelatinases. Half-maximal induction of PAI-1 mRNA or inhibition of fibronectin and thrombospondin mRNAs occurred with 2-5 micrograms/ml SPARC and approximately 0.05 mM SPARC4-23. Strains of endothelial cells that did not form cords and tubes in vitro had reduced or undetectable responses to SPARC under identical conditions. These results demonstrate that SPARC modulates the synthesis of a subset of secreted proteins and identify an N-terminal acidic sequence as a region of the protein that provides an active site. SPARC might therefore function, in part, to achieve an optimal ratio among different components of the extracellular matrix. This activity would be consistent with known effects of SPARC on cellular morphology and proliferation that might contribute to the regulation of angiogenesis in vivo.
Monoclonal-Antibody Therapy in Systemic Vasculitis (1990)

MONOCLONAL antibodies are potentially useful therapeutic agents in a variety of immunologically mediated diseases, offering the theoretical advantage of selective attack on cells implicated in the immunopathogenesis of these disorders. Antibodies to surface markers on lymphocytes, particularly T cells, have already demonstrated efficacy both in animal models and in clinical allograft rejection.1 2 3 For this purpose, monoclonal antibodies can be used either to block vital receptors for antigen, adhesion, or growth factors or to block target cells by harnessing the various natural effector systems (complement and accessory cells) that are activated by the Fc regions of cell-bound antibodies. The optimal use . . .
Longitudinal Analysis of Neural Network Development in Preterm Infants (2010)

Application of resting state functional connectivity magnetic resonance imaging (fcMRI) to the study of prematurely born infants enables assessment of the earliest forms of cerebral connectivity and characterization of its early development in the human brain. We obtained 90 longitudinal fcMRI data sets from a cohort of preterm infants aged from 26 weeks postmenstrual age (PMA) through term equivalent age at PMA-specific time points. Utilizing seed-based correlation analysis, we identified resting state networks involving varied cortical regions, the thalamus, and cerebellum. Identified networks demonstrated a regionally variable age-specific pattern of development, with more mature forms consisting of localized interhemispheric connections between homotopic counterparts. Anatomical distance was found to play a critical role in the rate of connection development. Prominent differences were noted between networks identified in term control versus premature infants at term equivalent, including in the thalamocortical connections critical for neurodevelopment. Putative precursors of the default mode network were detected in term control infants but were not identified in preterm infants, including those at term equivalent. Identified patterns of network maturation reflect the intricate relationship of structural and functional processes present throughout this important developmental period and are consistent with prior investigations of neurodevelopment in this population.
Regulation and mechanisms of macrophage cholesterol efflux (2002)

The accumulation of cholesterol in macrophage foam cells results from the uptake of retained and modified apoB lipoproteins (1) and is a central event in atherogenesis.Although it has long been known that HDL and its apolipoproteins can stimulate cholesterol efflux from macrophage foam cells (2, 3) and reduce atherogenesis in animal models (4, 5), this area of research has been enlivened by the elucidation of the genetic defect in Tangier disease, a condition in which there is a defect in apolipoprotein-mediated cholesterol efflux (6) and in which the hallmark pathology is the accumulation of macrophage foam cells in various tissues.Tangier disease is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1).This cell surface transporter facilitates the efflux of phospholipids and cholesterol onto lipid-poor apolipoproteins, initiating the formation of HDL particles.This Perspective will focus on recent studies on the regulation and role of ABCA1 in cellular cholesterol efflux, lipoprotein physiology, and atherogenesis, attempting to place this work in the broader context of studies on cellular cholesterol efflux, centripetal cholesterol transport, and ABC transporter structure and function.
Factor VIII-eGFP fusion proteins with preserved functional activity for the analysis of the early secretory pathway of factor VIII (2009)

Considering the difficulty in detecting factor (F)VIII in vivo, fluorescently labelled FVIII protein provides a tool to analyse the intracellular localisation, bio distribution, and pharmacokinetics of the protein in living organisms. Here, we report the use of FVIII full length and B-domain deleted proteins, fused to enhanced green fluorescent protein (eGFP) at the C-terminus of the coagulation protein via a nine amino acid spanning linker. Comparison of the FVIII-eGFP fusion proteins to their unlabelled counterparts showed no impairment with respect to recombinant expression levels, intracellular processing, specific coagulant activity and decay at physiological temperature. Confocal live cell imaging demonstrated ER-Golgi-transport of B-domain deleted FVIII-eGFP in vesicular tubular carriers. Using temperature blocks and release experiments, imaging of FVIII-eGFP fusion proteins enabled for the first time the visualisation of the early secretory pathway of B-domain deleted FVIII in living cells and in particular highlighted the apparent deficit of active transport carriers, an observation consistent with the low rates of FVIII secretion seen in recombinant expression systems.
Combined effects of vancomycin and imipenem against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo (1999)

Infectious disease caused by methicillin-resistant Staphylococcus aureus (MRSA) often develops in compromised hosts in whom a single administration of vancomycin is usually not effective. We assessed the combined antimicrobial effects of vancomycin and imipenem against MRSA growth in vitro as well as in vivo using a neutropenic mouse thigh infection model. Synergic and additive effects of the two drugs were observed for 34 and two, respectively, of the 36 clinical isolates of MRSA, as determined by the chequerboard method. For MRSA strain N, postantibiotic effect (PAE) values obtained in vitro were 1.9-2.6 h for vancomycin and 2.6-3.5 h for imipenem, while higher values of 2.7-4.4 h were obtained for the combination of vancomycin and imipenem. In vivo, a single administration of vancomycin at 1 or 2 mg/kg or of imipenem/cilastatin at 5 mg/kg produced growth curves similar to those in controls, with a suppressive time of 0 h. Imipenem/cilastatin at 10 mg/kg demonstrated a suppressive time of 3.1 h. Combinations of vancomycin 1 mg/kg plus imipenem/cilastatin 5 mg/kg, vancomycin 1 mg/kg plus imipenem/cilastatin 10 mg/k and vancomycin 2 mg/kg plus imipenem/cilastatin 10 mg/kg demonstrated suppressive times of 2.9, 3.9 and 5.2 h, respectively, indicating that combined administration was effective. Simultaneous administration of the two drugs was more effective than sequential administration. Thus, combined administration of vancomycin and imipenem/cilastatin proved effective for MRSA in vivo. The combined effects seemed to be synergic, since a single administration of either drug did not show anti-MRSA effects at the doses used in the combined regimen.
Atmospheric-Pressure Cold Plasma Induces Transcriptional Changes in Ex Vivo Human Corneas (2015)

These findings of transient oxidative stress accompanied by wide-range transcriptome adjustments support the further development of APCP as an ocular disinfectant.
Selectively Reduced Expression of Synaptic Plasticity-Related Genes in Amyloid Precursor Protein + Presenilin-1 Transgenic Mice (2003)

A critical question in Alzheimer's disease (AD) research is the cause of memory loss that leads to dementia. The amyloid precursor protein + presenilin-1 (APP+PS1) transgenic mouse is a model for amyloid deposition, and like AD, the mice develop memory deficits as amyloid deposits accumulate. We profiled gene expression in these transgenic mice by microarray and quantitative RT-PCR (qRT-PCR). At the age when these animals developed cognitive dysfunction, they had reduced mRNA expression of several genes essential for long-term potentiation and memory formation (Arc, Zif268, NR2B, GluR1, Homer-1a, Nur77/TR3). These changes appeared to be related to amyloid deposition, because mRNA expression was unchanged in the regions that did not accumulate amyloid. Transgene expression was similar in both amyloid-containing and amyloid-free regions of the brain. Interestingly, these changes occurred without apparent changes in synaptic structure, because a number of presynaptic marker mRNAs (growth-associated protein-43, synapsin, synaptophysin, synaptopodin, synaptotagmin, syntaxin) remained stable. Additionally, a number of genes related to inflammation were elevated in transgenic mice, primarily in the regions containing amyloid. In AD cortical tissue, the same memory-associated genes were downregulated. However, all synaptic and neuronal transcripts were reduced, implying that the loss of neurons and synapses contributed to these changes. We conclude that reduced expression of selected genes associated with memory consolidation are linked to memory loss in both circumstances. This suggests that the memory loss in APP+PS1 transgenic mice may model the early memory dysfunction in AD before the degeneration of synapses and neurons.
Noncompetitive flow injection immunoassay for a hapten, .alpha.-(difluoromethyl)ornithine (1993)

A noncompetitive flow injection immunoassay method has been developed to assay small haptens. In this assay the sample containing the hapten is incubated with excess enzyme-labeled monovalent antibody for a brief period. The excess antibody is then separated from the bound antibody by eluting through an antigen-immobilized immunoaffinity column. The enzyme label of the eluting antibody-hapten complex is fluorometrically detected. The applicability of the method is demonstrated by assaying alpha-(difluoromethyl)ornithine (DFMO), an anticancer drug in human plasma samples. The assay is sensitive enough to detect 200 amol of DFMO. Interferences from other similar endogenous amines have been eliminated by selective immunoaffinity purification of the antibodies.
Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes (1998)

It has been thought that lumbar intervertebral discs were innervated segmentally. We have previously shown that the L5-L6 intervertebral disc in the rat is innervated bilaterally from the L1 and L2 dorsal root ganglia through the paravertebral sympathetic trunks, but the pathways between the disc and the paravertebral sympathetic trunks were unknown. We have now studied the spines of 17 rats to elucidate the exact pathways. We examined serial sections of the lumbar spine using immunohistochemistry for calcitonin gene-related peptide, a sensory nerve marker. We showed that these nerve fibres from the intervertebral disc ran through the sinuvertebral nerve into the rami communicantes, not into the corresponding segmental spinal nerve. In the rat, sensory information from the lumbar intervertebral discs is conducted through rami communicantes. If this innervation pattern applies to man, simple decompression of the corresponding nerve root will not relieve discogenic pain. Anterior interbody fusion, with the denervation of rami communicantes, may be effective for such low back pain.
Potential of CXCR4 antagonists for the treatment of metastatic lung cancer (2011)

Despite advances in surgery, chemotherapy and radiotherapy over the last decades, the death rate from lung cancer has remained largely unchanged, which is mainly due to metastatic disease. Because of the overall poor prognosis, new treatment strategies for lung cancer patients are urgently needed, and targeting CXCR4 constitutes such a novel, attractive strategy. Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokine receptors and adhesion molecules. Lung cancer cells express CXCR4 (CD184), a seven-transmembrane G-protein-coupled chemokine receptor. Stromal cells within the tumor microenvironment constitutively secrete stromal cell-derived factor-1 (SDF-1/CXCL12), the ligand for CXCR4. Activation of CXCR4 induces lung cancer cell migration and adhesion to stromal cells, which in turn provides growth- and drug-resistance signals to the tumor cells. CXCR4 antagonists, such as Plerixafor (AMD3100) and T140 analogues (TN14003/BKT140), can disrupt CXCR4-mediated tumor cell adhesion to stromal cells and sensitize lung cancer cells to cytotoxic drugs. Therefore, targeting the CXCR4-CXCL12 axis is a novel, attractive therapeutic approach in small-cell lung cancer and non-small-cell lung cancer. In this article, we summarize data about the cellular and molecular microenvironment in small-cell lung cancer and non-small-cell lung cancer, as well as the role of CXCR4 in tumor-stroma crosstalk. In addition, we review the current status of the preclinical and clinical development of CXCR4 antagonists.
DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination (2017)

Canonical non-homologous end joining (c-NHEJ) repairs DNA double-strand breaks (DSBs) in G1 cells with biphasic kinetics. We show that DSBs repaired with slow kinetics, including those localizing to heterochromatic regions or harboring additional lesions at the DSB site, undergo resection prior to repair by c-NHEJ and not alt-NHEJ. Resection-dependent c-NHEJ represents an inducible process during which Plk3 phosphorylates CtIP, mediating its interaction with Brca1 and promoting the initiation of resection. Mre11 exonuclease, EXD2, and Exo1 execute resection, and Artemis endonuclease functions to complete the process. If resection does not commence, then repair can ensue by c-NHEJ, but when executed, Artemis is essential to complete resection-dependent c-NHEJ. Additionally, Mre11 endonuclease activity is dispensable for resection in G1. Thus, resection in G1 differs from the process in G2 that leads to homologous recombination. Resection-dependent c-NHEJ significantly contributes to the formation of deletions and translocations in G1, which represent important initiating events in carcinogenesis.
Antibodies against Phospholipids other than Cardiolipin: Potential Roles for Both Phospholipid and Protein (1996)

Autoantibodies to phospholipids other than cardiolipin have received less attention, to date, than anti-cardiolipin antibodies. This review focuses on these antibodies and potential roles for both phospholipid and protein in their reactivity. We review data in the literature indicating that antibodies to phosphatidylethanolamine and some lupus anticoagulant antibodies recognize phospholipid-binding proteins in association with phospholipid. Kininogens appear to be involved in the binding of antibodies to phosphatidylethanolamine, while phosphatidylserine-binding proteins, such as prothrombin and annexin V, have been implicated in lupus anticoagulant antibody recognition. These proteins bind to phospholipids that normally reside in the inner monolayer of the cell membrane, suggesting that exposure of these lipids is necessary for protein binding and antibody recognition to occur. In contrast, other autoantibodies, in particular those reactive with erythrocytes, appear to be directed at phospholipids that normally occur in the outer membrane leaflet, such as phosphatidylcholine. In summary, there is clearly accumulating evidence that antibodies to phospholipids other than cardiolipin recognize epitopes on phospholipid-binding proteins. It is not clear whether recognition of these epitopes is due to an increase in antigen density or a change in the protein or phospholipid structure, but it is likely that both protein and phospholipid structure play an important role in the in vivo interactions of these antibodies.
Evolution of dendritic patterns during alloy solidification: Onset of the initial instability (1998)

The evolution of a dendritic pattern from a planar solid-liquid interface during directional solidification of a binary alloy was investigated experimentally. The model alloy used was the transparent organic crystal succinonitrile doped with the laser dye coumarin 152. The buildup of solute ahead of the initially stable planar interface and the subsequent instability of the planar front were measured in detail and compared with recent theoretical calculations by Warren and Langer [Warren, J. A. & Langer, J. S. (1993) Phys. Rev. E 47, 2702- 2712]. The fluorescence of coumarin 152 was used for direct observations of the evolution of the solute concentration profile ahead of the initially planar solid-liquid interface. UV absorption was used to produce thermal perturbations of the sample that generated spatially periodic modulations of the planar interface. This technique allows for measurement of both positive and negative linear growth coefficients (determined from the growth or decay rate of the modulation after the perturbation is switched off) for a large range of wave vectors. Measurements of the evolution of the concentration profile and the linear growth coefficients, and the occurrence of the initial instability, were in good agreement with the Warren-Langer predictions.
Towards the synthesis of epothilone A: Enantioselective preparation of the thiazole sidechain and macrocyclic ring closure (1997)

A synthetic approach to a new class of microtubule-stabilizing natural products is described which employs a macrocyclic olefination strategy to cyclize the 16-membered lactone ring. The C13C19 thiazole subunit of epothilone A and B is prepared in high enantioselectivity using a catalytic asymmetric allylation reaction.
Translational Regulation and RNA Localization in Drosophila Oocytes and Embryos (2001)

Translational control is a prevalent means of gene regulation during Drosophila oogenesis and embryogenesis. Multiple maternal mRNAs are localized within the oocyte, and this localization is often coupled to their translational regulation. Subsequently, translational control allows maternally deposited mRNAs to direct the early stages of embryonic development. In this review we outline some general mechanisms of translational regulation and mRNA localization that have been uncovered in various model systems. Then we focus on the posttranscriptional regulation of four maternal transcripts in Drosophila that are localized during oogenesis and are critical for embryonic patterning: bicoid (bcd), nanos (nos), oskar (osk), and gurken (grk). Cis- and trans-acting factors required for the localization and translational control of these mRNAs are discussed along with potential mechanisms for their regulation.