gebhart/patrepeval huggingface dataset:
Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways (2006)

Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation is central at all stages of atherosclerosis. It is implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium. It also acts at the onset of adverse clinical vascular events, when activated cells within the plaque secrete matrix proteases that degrade extracellular matrix proteins and weaken the fibrous cap, leading to rupture and thrombus formation. Cells involved in the atherosclerotic process secrete and are activated by soluble factors, known as cytokines. Important recent advances in the comprehension of the mechanisms of atherosclerosis provided evidence that the immunoinflammatory response in atherosclerosis is modulated by regulatory pathways, in which the two anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta play a critical role. The purpose of this review is to bring together the current information concerning the role of cytokines in the development, progression, and complications of atherosclerosis. Specific emphasis is placed on the contribution of pro- and anti-inflammatory cytokines to pathogenic (innate and adaptive) and regulatory immunity in the context of atherosclerosis. Based on our current knowledge of the role of cytokines in atherosclerosis, we propose some novel therapeutic strategies to combat this disease. In addition, we discuss the potential of circulating cytokine levels as biomarkers of coronary artery disease.
Soluble CD40L and Cardiovascular Risk in Women (2001)

High plasma concentrations of sCD40L may be associated with increased vascular risk in apparently healthy women.
Effect of Respiration on Venous Return and Stroke Volume in Cardiac Tamponade (1967)

In 40 lightly anesthetized dogs, 5 to 30 days after surgical preparation, flow was measured simultaneously in the venae cavae, pulmonary artery, pulmonary vein, and aorta with ultrasonic flowmeters. Intrapleural and pericardial pressures were measured via silastic cannulas. Pulmonary vein diameter was monitored by miniature mutual inductance coils. In the resting animal with sinus arrhythmia, inspiration increased heart rate and flow in the vena cava, and to a lesser extent, in the pulmonary vein. Left ventricular stroke volume (LVSV) varied directly with the right ventricular stroke volume (RVSV) in dogs with slow heart rates. Cardiac tamponade invariably caused tachycardia and a marked decrease in cardiac output, arterial pressure, pulse pressure, and stroke volume; venous pressure and diameter increased. Pericardial pressure, although markedly elevated, fell with inspiration paralleling the fall in intrapleural pressure. Flow in the pulmonary vein rose or remained constant with inspiration. Pulmonary vein diameter frequently increased with inspiration during tamponade, but only after the pulmonary artery diameter increased with the inspiratory surge. LVSV did not decline sharply with inspiration, and actually increased within 2 beats of the increase in RVSV. The sum of LVSV plus RVSV increased markedly with inspiration, contradicting the concept of fixed intrapericardial volume. Almost all of the changes of pulsus paradoxus reflect the normal respiratory effects on the RVSV, delayed by transit through the pulmonary bed and exaggerated by the small LVSV in a vasoconstricted state.
Synthesis of N29-desmethyl RA-VII. Identification of the pharmacophore of RA-I-VII and deoxybouvardin and reassignment of the subunit functional roles (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of N29-desmethyl RA-VII. Identification of the pharmacophore of RA-I-VII and deoxybouvardin and reassignment of the subunit functional rolesDale L. Boger, Daniel Yohannes, and James B. Myers Jr.Cite this: J. Org. Chem. 1992, 57, 5, 1319–1321Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/jo00031a001https://doi.org/10.1021/jo00031a001research-articleACS PublicationsRequest reuse permissionsArticle Views123Altmetric-Citations20LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Immunogenicity and epitope mapping of foreign sequences via genetically engineered filamentous phage. (1988)

Repeat regions of the circumsporozoite protein gene of Plasmodium falciparum were cloned into the pIII gene of a filamentous phage. These genetically engineered filamentous phage display the recombinant proteins on their surface. We demonstrate that they are both antigenic and immunogenic in rabbits. The recombinant phage were shown to be useful as a source of antigen for this scarce malaria protein, for producing carrier-hapten conjugates for obtaining immunological reagents in rabbits, and for B epitope mapping. In addition, in mice the antibody response to the cloned antigens seems to be controlled by immune response genes. Therefore this system also has the potential for use in helper T cell epitope mapping using inbred mouse strains. This advantage will be of use in vaccine development.
Application of Personal Computers in Engineering (1985)

A number of self-contained personal computers have been in use at the Engineering Headquarters of the Canadian Broadcasting Corp. for three years. The uses to which they are put and the reasons for using them are discussed, with emphasis on why similar results would not be achieved so conveniently with large mainframe computers. Staff training and the control of program development are described, and some samples of current programs are included.
Increased transfer of iron to the fetus after total dose infusion of iron dextran during pregnancy. (1983)

After total dose infusion of iron dextran to 14 pregnant women the saturation of transferrin and the concentration of ferritin were increased in the cord blood at birth, compared with untreated cases. These changes suggest that the fetal iron stores may be increased by such treatment.
PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes (2005)

PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family essential for mammalian transcription and development. Although these complexes share eight identical subunits, only PBAF can facilitate transcriptional activation by nuclear receptors in vitro. Here we show that these complexes have selectivity in mediating transcription of different interferon-responsive genes. The selectivity by PBAF requires a novel subunit, BAF200, but not the previously described PBAF-specificity subunit, BAF180 (Polybromo). Our study provides in vivo evidence that PBAF and BAF regulate expression of distinct genes, and suggests that BAF200 plays a key role in PBAF function.
Applicability of an absolute quantitative procedure to monitor intra‐individual bcrabl transcript kinetics in clinical samples from chronic myelogenous leukemia patients (2000)

Chimeric bcr/abl fusion proteins are thought to be the molecular 'pathogen' of chronic myelogenous leukaemia (CML). Expression levels of the respective fusion RNAs reflect disease progression as well as remission upon therapeutic intervention in CML patients. However, there is no quick and reliable method that would allow the quantitative routine monitoring of bcr/abl hybrid transcripts. A fluorescent probe-based PCR assay (TaqMan) has been described to quantitfy the exact amount of target sequences. We have established TaqMan real-time RT-PCRs for M-bcr/abl (b2a2, b2a3, b3a2, b3a3) and m-bcr/abl (e1a2) fusion transcripts as well as for β-actin. All PCRs quantified as little as 10 copies/100 ng total cDNA. In order to investigate whether this procedure is appropriate for routine diagnostic monitoring, we performed retrospective measurements on 9 documented CML disease courses. Our data show that ongoing or relapsing CML is paralleled by increasing peripheral levels of bcr/abl fusion RNAs. Furthermore, sucessful anti-leukemic treatment is reflected by decreasing absolute bcr/abl transcript numbers. In contrast with conventional bcr/abl PCR techniques we could distinguish single positive values and gradually increasing copy numbers. Int. J. Cancer 86:741–746, 2000. © 2000 Wiley-Liss, Inc.
Both CRISPR/Cas‐based nucleases and nickases can be used efficiently for genome engineering in Arabidopsis thaliana (2014)

Engineered nucleases can be used to induce site-specific double-strand breaks (DSBs) in plant genomes. Thus, homologous recombination (HR) can be enhanced and targeted mutagenesis can be achieved by error-prone non-homologous end-joining (NHEJ). Recently, the bacterial CRISPR/Cas9 system was used for DSB induction in plants to promote HR and NHEJ. Cas9 can also be engineered to work as a nickase inducing single-strand breaks (SSBs). Here we show that only the nuclease but not the nickase is an efficient tool for NHEJ-mediated mutagenesis in plants. We demonstrate the stable inheritance of nuclease-induced targeted mutagenesis events in the ADH1 and TT4 genes of Arabidopsis thaliana at frequencies from 2.5 up to 70.0%. Deep sequencing analysis revealed NHEJ-mediated DSB repair in about a third of all reads in T1 plants. In contrast, applying the nickase resulted in the reduction of mutation frequency by at least 740-fold. Nevertheless, the nickase is able to induce HR at similar efficiencies as the nuclease or the homing endonuclease I-SceI. Two different types of somatic HR mechanisms, recombination between tandemly arranged direct repeats as well as gene conversion using the information on an inverted repeat could be enhanced by the nickase to a similar extent as by DSB-inducing enzymes. Thus, the Cas9 nickase has the potential to become an important tool for genome engineering in plants. It should not only be applicable for HR-mediated gene targeting systems but also by the combined action of two nickases as DSB-inducing agents excluding off-target effects in homologous genomic regions.
Morphological evidence for penetration of anti-O antibody through the capsule of Klebsiella pneumoniae (1990)

The role of the capsule in the reaction with anti-O or anti-K serum was examined morphologically by the techniques of freeze-substitution and immunoelectron microscopy in two strains of Klebsiella pneumoniae differing in virulence for mice. Strain Chedid (O1:K2), an encapsulated virulent strain, has a thicker capsule (150 nm) than the encapsulated avirulent strain 277 (O1:K2) (60 nm). Two morphologically recognizable domains in the capsule created by the arrangement of the capsular filaments were clearly seen in strain Chedid but were less evident in strain 277. Anti-O antibody could penetrate through the capsular layer of both strains. The capsule has no function as a barrier for the penetration of the antibody. Anti-K antibody reacted only on the surface of the capsule and induced swelling of the capsule.
Site-directed mutagenesis and expression of PC2 in microinjected Xenopus oocytes. (1991)

The biosynthesis and post-translational maturation of PC2, a neuroendocrine-specific Kex2-like endoprotease, following expression in Xenopus oocytes is described. The initial translation product was a 75-kDa membrane-associated protein which was released from the oocytes as a glycosylated 71-kDa protein. During extended chase periods, the extracellular 71-kDa protein was converted to a mature 68-kDa product. A deletion mutant lacking a putative COOH-terminal amphipathic helix was still membrane-associated, suggesting that this domain was not essential for attachment of PC2 to membranes. Two putative proregion cleavage site mutants were also constructed. Conversion of the 75-kDa peptide to the 71-kDa peptide involved cleavage at the sequence Lys-Arg-Arg-Arg (amino acids 78-81), since mutation of this sequence to Lys-Val-Arg-Leu resulted in the secretion of the 75-kDa peptide. Extracellular conversion of the 71-kDa peptide to the 68-kDa peptide involved cleavage at the sequence Arg-Lys-Lys-Arg (amino acids 106-109), since deletion of this tetrabasic sequence resulted in secretion of the 71-kDa peptide without further conversion to the 68-kDa form. Finally, a mutation which changed a catalytically important Asp to Asn did not affect processing of proPC2. These results may be relevant to our understanding of mechanisms in the intracellular sorting and maturation of proPC2 in neuroendocrine cells.
CAD reference flow for 3D via-last integrated circuits (2010)

Next-decade computing power and interconnect bottle-neck challenge conventional IC design due to the ever increasing demands for high frequency and great bandwidth. Three-dimensional large-scale integration (3D-LSI) provides an opportunity to realize such high performance cores while reducing long latency. In this paper, we present a reference flow for the implementation of 3D via-last ICs in scalable face-to-back bonding style which leverages a mature set of 2D IC physical design tools. The first enabling technology of 3D-LSI is through-silicon via (TSV). Two kinds of TSV diameters are exemplified in the flow, namely, 5µm and 50µm. We propose an easy-to-adopt method to address the TSV-aware mixed-sized placement by considering the obstructions generated from adjacent-tier's floorplan, subject to certain TSV alignment constraints. Furthermore, the technique of clock tree synthesis (CTS) for a homogeneous die stack is developed to dramatically reduce the clock latency and skew. The mixed-sized placement and CTS of each tier can be done without iteration. To the best of our knowledge, no work has ever been published in literature discussing CTS for 3D via-last integration in a face-to-back fashion. Finally, to complete the proposed flow 2D timing-driven routing and modified off-line design rule check (DRC) and layout versus schematic (LVS) verification are performed very well.
Hydrogen sulfide downregulates the aortic l-arginine/nitric oxide pathway in rats (2007)

The aim of the present study was to investigate the effect of hydrogen sulfide (H(2)S) signaling by nitric oxide (NO) in isolated rat aortas and cultured human umbilical vein endothelial cells (HUVECs). Both administration of H(2)S and NaHS, as well as endogenous H(2)S, reduced NO formation, endothelial nitric oxide synthase (eNOS) activity, eNOS transcript abundance, and l-arginine (l-Arg) transport (all P < 0.01). The kinetics analysis of eNOS activity and l-Arg transport showed that H(2)S reduced V(max) values (all P < 0.01) without modifying K(m) parameters. Use of selective NOS inhibitors verified that eNOS [vs. inducible NOS (iNOS) and neuronal NOS (nNOS)] was the specific target of H(2)S regulation. H(2)S treatment (100 micromol/l) reduced Akt phosphorylation and decreased eNOS phosphorylation at Ser1177. H(2)S reduced l-Arg uptake by inhibition of a system y+ transporter and decreased the CAT-1 transcript. H(2)S treatment reduced protein expression of eNOS but not of nNOS and iNOS. Pinacidil (K(ATP) channel opener) exhibited the similar inhibitory effects on the l-Arg/NOS/NO pathway. Glibenclamide (K(ATP) channel inhibitor) partly blocked the inhibitory effect of H(2)S and pinacidil. An in vivo experiment revealed that H(2)S downregulated the vascular l-Arg/eNOS/NO pathway after intraperitoneal injection of NaHS (14 micromol/kg) in rats. Taken together, our findings suggest that H(2)S downregulates the vascular l-Arg/NOS/NO pathway in vitro and in vivo, and the K(ATP) channel could be involved in the regulatory mechanism of H(2)S.
Growth and activities of sulphate-reducing bacteria in gut contents of healthy subjects and patients with ulcerative colitis (1991)

During fermentation in the human large intestine, terminal oxidative processes may involve the activities of dissimilatory sulphate-reducing bacteria (SRB).Approximately 50% of healthy individuals harbour significant populations of SRB in faeces.In mixed culture, growth of SRB in vitro was modulated by sulphate availability, with sulphated polysaccharides such as mucin, chondroitin sulphate and carrageenan causing increased growth rates and sulphide production when compared with starch, pectin and arabinogalactan.Rates of H,S production were higher among SRB isolated from patients with ulcerative colitis in contrast to those present in healthy volunteers.The majority (up to 92%) of SRB in faecal samples belonged to the genus Desulfouibrio.In vitro studies demonstrated that compared to isolates from healthy subjects, Desulfovibrio
Kinetics and sequence specificity of drug-DNA interactions: an in vitro transcription assay (1986)

An assay has been developed to detect the DNA sequence specificity of drug binding sites, and the kinetics of dissociation of drug from those sites, under conditions involving active transcription of the DNA. Specific transcriptional blockage sites were detected in the presence of actinomycin D and a bisintercalator, bis(anthracycline); the rate of RNA chain growth past the drug binding sites yields the rate of dissociation of drug from these sites. Rate constants for dissociation from the whole promoter fragment measured by the detergent sequestration method were found to be significantly faster than the rate determined for dissociation from the specific transcriptional blockage site. However, the absence of significant blockage at other drug binding sites implies much more rapid drug dissociation from those sites in the transcriptional complex. We conclude that transcriptional blockage results from a DNA sequence-dependent interaction of the drug-DNA complex with RNA polymerase; the sequences that are effective for blockage appear to be GpC for actinomycin and (CpA)3 for a bis(daunomycin) compound. Transcriptional inhibition may in general show greater sequence specificity than is exhibited by simple binding.
Identification of neural circuits underlying P300 abnormalities in schizophrenia (1999)

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.
Neutrophil Fc gamma RIIIb deficiency, nature, and clinical consequences: a study of 21 individuals from 14 families (1995)

Several individuals have been described whose neutrophils lack the normally abundantly expressed IgG Fc gamma receptor IIIb (Fc gamma RIIIb). We now studied the responsible genomic defect and analyzed the medical history in detail of 21 Fc gamma RIIIb-negative donors identified in 14 unrelated families. We developed a polymerase chain reaction allele-specific-primer annealing assay to genotype for the NA polymorphism of the Fc gamma RIIIB gene. All Fc gamma RIIIb-deficient individuals were negative for both the NA1 and the NA2 allele. In all cases the complete absence of the Fc gamma RIIIB alleles was confirmed using a Southern blot-based restriction fragment length polymorphism assay. Furthermore, an additional deletion of the next more telomeric located Fc gamma RIIC gene was found. Family studies showed that at least one Fc gamma RIIIB allele was absent in both parents in 6 families, whereas in 2 families the father had a normal phenotype. Two individuals suffered from an autoimmune thyroiditis. Four individuals had had multiple episodes of infection, 3 had only incidental infections, and 14 never had any serious infection. Genotyping showed a normal Fc gamma RIIa phenotype distribution among the Fc gamma RIIIb-negative individuals, thus excluding the possibility that the presence of the favorable IgG2-binding low-responder isoform of Fc gamma RIIa (131-H) contributed to the overall absence of recurrent bacterial infections.
Arylamine toxins from funnel-web spider (Agelenopsis aperta) venom antagonize N-methyl-D-aspartate receptor function in mammalian brain. (1991)

The venom of the North American funnel-web spider Agelenopsis aperta contains a variety of arylamine toxins (the alpha-agatoxins) that paralyze insects by blocking glutamatergic neuromuscular transmission. We have tested six synthetic alpha-agatoxins for their ability to antagonize glutamate receptor function in mammalian brain. These compounds produce, at submicromolar concentrations, noncompetitive inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated elevations in the concentration of cytosolic free calcium in cultured rat cerebellar granule neurons. In contrast, the alpha-agatoxins are relatively weak antagonists of elevations in the cytosolic free calcium concentration induced by non-NMDA receptor agonists. The alpha-agatoxins also produce reversible suppression of the NMDA receptor-mediated excitatory postsynaptic potential in rat hippocampal slices at concentrations that have little effect on the non-NMDA receptor-mediated population spike. We conclude that the alpha-agatoxins are selective and reversible noncompetitive antagonists at NMDA receptors in mammalian brain.
The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. (1994)

A number of inflammatory disease states occur with greatly increased frequency in individuals inheriting the human major histocompatibility complex class I allele HLA-B27. In a minority of cases, namely those with B27-associated reactive arthritis, there is good evidence that the disease state is triggered by infection with an enteric or genitourinary bacterial pathogen. For the majority of B27-associated disease, no definite pathogenetic role for bacteria has been established. However, in these latter cases intestinal inflammation can often be demonstrated, and it sometimes occupies a major part of the clinical picture. Rats transgenic for B27 are known to develop a disorder resembling B27-associated human disease, with prominent intestinal, joint, skin, and male genital inflammatory lesions. We report here that B27 transgenic rats raised in a germfree environment do not develop inflammatory intestinal or peripheral joint disease, whereas the skin and genital inflammatory lesions are unaffected by the germfree state. These findings support the concept that gut and joint inflammation are pathogenetically closely related, and they provide direct evidence that the commensal gut flora play an important role in the pathogenesis of B27-associated gut and joint inflammation.