gebhart/patrepeval huggingface dataset:
The Immunology of Macrophage Activation Syndrome (2019)

Synonymous with secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome (MAS) is a term used by rheumatologists to describe a potentially life-threatening complication of systemic inflammatory disorders, most commonly systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus (SLE). Clinical and laboratory features of MAS include sustained fever, hyperferritinemia, pancytopenia, fibrinolytic coagulopathy, and liver dysfunction. Soluble interleukin-2 receptor alpha chain (sCD25) and sCD163 may be elevated, and histopathology often reveals characteristic increased hemophagocytic activity in the bone marrow (and other tissues), with positive CD163 (histiocyte) staining. A common hypothesis as to the pathophysiology of many cases of MAS proposes a defect in lymphocyte cytolytic activity. Specific heterozygous gene mutations in familial HLH-associated cytolytic pathway genes (e.g., <i>PRF1, UNC13D</i>) have been linked to a substantial subset of MAS patients. In addition, the pro-inflammatory cytokine environment, particularly IL-6, has been shown to decrease NK cell cytolytic function. The inability of NK cells and cytolytic CD8 T cells to lyse infected and otherwise activated antigen presenting cells results in prolonged cell-to-cell (innate and adaptive immune cells) interactions and amplification of a pro-inflammatory cytokine cascade. The cytokine storm results in activation of macrophages, causing hemophagocytosis, as well as contributing to multi-organ dysfunction. In addition to macrophages, dendritic cells likely play a critical role in antigen presentation to cytolytic lymphocytes, as well as contributing to cytokine expression. Several cytokines, including tumor necrosis factor, interferon-gamma, and numerous interleukins (i.e., IL-1, IL-6, IL-18, IL-33), have been implicated in the cytokine cascade. In addition to broadly immunosuppressive therapies, novel cytokine targeted treatments are being explored to dampen the overly active immune response that is responsible for much of the pathology seen in MAS.
Gene Coexpression Network Topology of Cardiac Development, Hypertrophy, and Failure (2010)

Network modeling allows systems analysis of cardiovascular development and disease. Although we did not find evidence for a global coordinated program of fetal gene expression in adult myocardial adaptation, our analysis revealed specific gene expression modules active during both development and disease and specific candidates for their regulation.
Laser Raman molecular microprobe (MOLE) (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLaser Raman molecular microprobe (MOLE)P. Dhamelincourt, F. Wallart, M. Leclercq, A. T. Nguyen, and D. O. LandonCite this: Anal. Chem. 1979, 51, 3, 414A–420APublication Date (Print):March 1, 1979Publication History Published online21 September 2008Published inissue 1 March 1979https://pubs.acs.org/doi/10.1021/ac50039a002https://doi.org/10.1021/ac50039a002research-articleACS PublicationsRequest reuse permissionsArticle Views157Altmetric-Citations71LEARN 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
Asymptotic properties of the least-squares method for estimating transfer functions and disturbance spectra (1992)

The problem of estimating the transfer function of a linear system, together with the spectral density of an additive disturbance, is considered. The set of models used consists of linear rational transfer functions and the spectral densities are estimated from a finite-order autoregressive disturbance description. The true system and disturbance spectrum are, however, not necessarily of finite order. We investigate the properties of the estimates obtained as the number of observations tends to ∞ at the same time as the model order employed tends to ∞. It is shown that the estimates are strongly consistent and asymptotically normal, and an expression for the asymptotic variances is also given. The variance of the transfer function estimate at a certain frequency is related to the signal/noise ratio at that frequency and the model orders used, as well as the number of observations. The variance of the noise spectral estimate relates in a similar way to the squared value of the true spectrum.
Radical scavengers for Ménière's disease after failure of conventional therapy: a pilot study (2003)

This study suggests that treatment using radical scavengers has the potential to become an effective new therapy for MD.
MOLECULAR DIAGNOSIS OF THIOPURINE S-METHYLTRANSFERASE DEFICIENCY AS A GUIDE TO 6-MERCAPTOPURINE THERAPY IN CHILDHOOD IBD (1998)

10 Thiopurine S-methyltransferase (TPMT) is the major enzyme controlling metabolism of 6-mercaptopurine (6-MP). Low TPMT activity results in enhanced production of 6-TG and dose-dependent toxicity. High TPMT activity results in reduced therapeutic efficacy with 6-MP therapy. Eleven percent of the population has intermediate TPMT activity and 1:300 are TPMT deficient. The most common allelic variants of the TPMT gene responsible for reduced TPMT activity have been identified. We have previously reported preliminary data showing a low incidence of TPMT deficiency in IBD. We have now genotyped a large group of pediatric IBD patients and controls to determine the incidence of TPMT deficiency and have correlated TPMT genotyping with 6-MP toxicity and with RBC TPMT enzyme activity. TPMT genotyping was performed by restriction enzyme digestion of PCR-amplified DNA extracted from buccal brushings. Two of 50 IBD patients (4%) and five of 44 controls (11%) were found to carry low activity TPMT alleles. Twenty-eight of the 50 IBD patients had been treated with 6-MP or AZA. Five had experienced pancreatitis, hepatitis, or both associated with 6-MP therapy, none of which were found to have TPMT-deficient alleles. In preliminary studies in a control group, genotyping was 100% sensitive and specific for the determination of normal or low RBC TPMT activity. RBC TPMT activity was normal in 1 IBD patient with normal genotyping who had experienced pancreatitis and was above the normal range for 1 IBD patient with normal genotyping who had not been treated with 6-MP. These data suggest that TPMT deficiency may be less frequent in the IBD population than in the general population. Genotyping is predictive of low TPMT enzyme activity, but does not distinguish between the high and low ends of the normal TPMT activity range. Pancreatitis with 6-MP therapy does not appear to relate to TPMT activity. The combination of TPMT genotyping and enzyme assay may be useful for identifying patients at risk for dose-dependent toxicity and those who may need increases in dosage for therapeutic efficacy. (Supported by a grant from the Nemours Foundation)
Nucleoside hydrolases from Trypanosoma cruzi. (1984)

Four distinct nucleoside cleaving enzymes were detected in extracts of Trypanosoma cruzi epimastigotes. Two of these were nucleoside phosphorylases: one was specific for pyrimidines and the other for purines. The other two enzymes were nucleoside hydrolases. These hydrolytic enzymes were partially purified and their substrate and inhibitor specificities were studied. One of the hydrolases was designated inosine/guanosine hydrolase. It required purine substrates containing a 9-beta-D-ribofuranosyl substituent. Neither 2'-deoxyinosine, 2'-deoxyguanosine, nor hypoxanthine arabinoside served as substrates. The kinetic patterns obtained from combined product analysis and the mutual competitive inhibition of this enzyme by inosine and guanosine suggested that these substrates were cleaved at a common catalytic site. Inhibitor studies with several deoxyinosines have demonstrated the importance of the 2'-, 3'-, and 5'-hydroxyl groups for efficient binding to the enzyme. Adenosine, which did not serve as a substrate, was a potent competitive inhibitor (Ki = 8 microM) with respect to both inosine and guanosine. This enzyme had a particle weight of 106,000 +/- 10,000 as determined by Sephadex chromatography. The other hydrolase was specific for 2'-deoxyinosine. It only accepted purine substrates with a 6-oxo- and a 9-beta-D-2'-deoxyribofuranosyl substituent. Inosine, hypoxanthine arabinoside and a variety of deoxyinosines were not substrates nor did they strongly inhibit this enzyme. This enzyme had a particle weight of 19,000 +/- 2,000 as determined by Sephadex chromatography.
Quantitative Trait Loci Associated With Adventitious Shoot Formation in Tissue Culture and the Program of Shoot Development in Arabidopsis (2004)

Arabidopsis ecotypes, Columbia (Col) and Landsberg erecta (Ler), differ in their capacity to regenerate shoots in culture, as do many other cultivars and varieties of the same plant species. Recombinant inbred (RI) lines derived from a cross of Col x Ler were scored for shoot regeneration, and the Arabidopsis genome was scanned using composite interval mapping for loci associated with shoot regeneration. Three QTL were identified--a major one on chromosome 5 in which the Col parent contributed the superior allele and two minor QTL on chromosomes 1 and 4 in which the Ler parent contributed the superior alleles. The RI lines were binned into genotypic pools to isolate the effects of the major QTL on chromosome 5 while holding the minor QTL constant. To identify genes with expression levels that are associated with the allelic state of the major QTL on chromosome 5, oligonucleotide array expression patterns for genes in the LLC pool (Ler alleles at the minor QTL and a Col allele at the major QTL) were compared to those in the LLL pool (Ler alleles at all QTL). The genes that were significantly differentially expressed between the two pools included several encoding transcription factors and signaling or transposon-related proteins.
Monte Carlo Smoothing for Nonlinear Time Series (2004)

We develop methods for performing smoothing computations in general state-space models. The methods rely on a particle representation of the filtering distributions, and their evolution through time using sequential importance sampling and resampling ideas. In particular, novel techniques are presented for generation of sample realizations of historical state sequences. This is carried out in a forward-filtering backward-smoothing procedure that can be viewed as the nonlinear, non-Gaussian counterpart of standard Kalman filter-based simulation smoothers in the linear Gaussian case. Convergence in the mean squared error sense of the smoothed trajectories is proved, showing the validity of our proposed method. The methods are tested in a substantial application for the processing of speech signals represented by a time-varying autoregression and parameterized in terms of time-varying partial correlation coefficients, comparing the results of our algorithm with those from a simple smoother based on the filtered trajectories.
KVLQT1 mutations in three families with familial or sporadic long QT syndrome (1996)

Congenital long QT syndrome (LQTS) is a heterogeneous group of heritable disorders characterized by prolongation of the QT interval on the electrocardiogram, ventricular arrhythmias and sudden death. At least four genes can, when mutated, produce this phenotype. Of these genes, the recently identified KVLQT1 potassium channel is thought to be the one most commonly responsible. In this study, we used single strand conformational polymorphism (SSCP) analysis to screen two large and nine small LQTS families for mutations of the KVLQT1 potassium channel gene. We identified a novel missense mutation in two unrelated families which substitutes a serine for a conserved glycine in the putative pore region of the KVLQT1 channel. In a third family, a new alanine to valine mutation at a CpG dinucleotide resulted in the spontaneous occurrence of the long QT syndrome in monozygotic twin offspring of unaffected parents. Mutations at this same nucleotide have been observed in eight of the 19 LQTS families determined to have KVLQT1 mutations, suggesting this is a mutational hot spot. Both of these mutations alter the amino acid sequence in, or adjacent to, the pore of the channel and many diminish the channel's ability to conduct a repolarizing potassium current. To date, all KVLQT1 mutations determined to cause the LQTS are missense mutations. These data confirm the role of KVLQT1 in the LQTS and suggest that mutant KVLQT1 proteins may exert a dominant negative effect on repolarizing potassium currents by forming multimers with normal potassium channel protein subunits, dramatically reducing the number of fully-functional KVLQT1 channels.
Repeat-induced gene silencing: common mechanisms in plants and fungi. (1996)

One of the most surprising observations made in plant science in recent years is the inactivation of transgenes triggered by interactions between DNA repeats. In plants, we can differentiate between transcriptional silencing, most likely reflecting a regulation at the DNA level, and post-transcriptional silencing that affects steady state RNA levels. In the filamentous fungi Ascobolus immersus and Neurospora crassa, we find two premeiotic silencing processes that are also based on the interaction of repeated sequences. A common feature of transcriptional silencing in plants and premeiotic gene inactivation in filamentous fungi is that the repeated sequences undergo cytosine methylation. DNA methylation, which is either the cause or the consequence of gene silencing, can be associated with changes in chromatin structure. These structural changes are reminiscent of homology-based silencing mechanisms in Drosophila, an organism that lacks DNA methylation. Repeat-induced silencing may therefore reflect the activity of an endogenous mechanism, present in some species, which screens for homology and has significant implications for the organization and evolution of the genome.
Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes. (1990)

Recognition of an AUG initiator codon in a suboptimal context improves when a modest amount of secondary structure is introduced near the beginning of the protein-coding sequence. This facilitating effect depends on the position of the downstream stem-loop (hairpin) structure. The strongest facilitation is seen when the hairpin is separated from the preceding AUG codon by 14 nucleotides. Because 14 nucleotides corresponds to the approximate distance between the leading edge of the ribosome and its AUG-recognition center as measured by ribonuclease protection experiments, a likely explanation for the enhancing effect of a downstream hairpin is that secondary structure slows scanning, thereby providing more time for recognition of the AUG codon, and the facilitation is greatest when the 40S ribosome stalls with its AUG-recognition center directly over the AUG. The variable ability of mammalian ribosomes to initiate at non-AUG codons in vitro is also explicable by the presence or absence of a stem-loop structure just downstream from the alternative initiator codon. This may be relevant to recent reports of adventitious upstream initiation events at non-AUG codons in some vertebrate mRNAs that have structure-prone, G + C-rich leader sequences.
Miniature real-time intraoperative forward-imaging optical coherence tomography probe (2013)

Optical coherence tomography (OCT) has a tremendous global impact upon the ability to diagnose, treat, and monitor eye diseases. A miniature 25-gauge forward-imaging OCT probe with a disposable tip was developed for real-time intraoperative ocular imaging of posterior pole and peripheral structures to improve vitreoretinal surgery. The scanning range was 2 mm when the probe tip was held 3-4 mm from the tissue surface. The axial resolution was 4-6 µm and the lateral resolution was 25-35 µm. The probe was used to image cellophane tape and multiple ocular structures.
Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine (2021)

The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate. (Funded by Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services; COV1001 ClinicalTrials.gov number, NCT04436276.).
Tumor growth suppression by a retroviral vector displaying scFv antibody to CEA and carrying the iNOS gene. (2002)

This approach may also be applied to other tumor antigens expressed on cancer cells and is a step towards the cell specific suppression of tumorigenicity.
A general template-based method for the preparation of nanomaterials (1997)

This article reviews a general template-based approach for the preparation of nanomaterials. The method involves the synthesis of a desired material within the pores of a nanoporous membrane. We have termed this approach ‘template synthesis’ because the pores within these nanoporous membranes act as templates for the synthesis of nanostructures of the desired material. Because the pores within these membranes are cylindrical and of uniform diameter, monodisperse nanocylinders of the desired material are obtained. Depending on the chemistry of the pore wall and material, these nanocylinders may be either hollow (a tubule) or solid (a fibril or nanowire). This template process will be shown to be a very general approach in the fabrication of nanotubes and fibrils composed of a variety of materials including polymers, metals, semiconductors, carbons, and other materials.
PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. (2000)

PTK787/ZK 222584 (1-[4-chloroanilino]-4-[4-pyridylmethyl] phthalazine succinate) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, active in the submicromolar range. It also inhibits other class III kinases, such as the platelet-derived growth factor (PDGF) receptor beta tyrosine kinase, c-Kit, and c-Fms, but at higher concentrations. It is not active against kinases from other receptor families, such as epidermal growth factor receptor, fibroblast growth factor receptor-1, c-Met, and Tie-2, or intracellular kinases such as c-Src, c-Abl, and protein kinase C-alpha. PTK787/ZK 222584 inhibits VEGF-induced autophosphorylation of kinase insert domain-containing receptor (KDR), endothelial cell proliferation, migration, and survival in the nanomolar range in cell-based assays. In concentrations up to 1 microM, PTK787/ZK 222584 does not have any cytotoxic or antiproliferative effect on cells that do not express VEGF receptors. After oral dosing (50 mg/kg) to mice, plasma concentrations of PTK787/ZK 222584 remain above 1 microM for more than 8 h. PTK787/ZK 222584 induces dose-dependent inhibition of VEGF and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, it also inhibits the growth of several human carcinomas, grown s.c. in nude mice, as well as a murine renal carcinoma and its metastases in a syngeneic, orthotopic model. Histological examination of tumors revealed inhibition of microvessel formation in the interior of the tumor. PTK787/ZK 222584 is very well tolerated and does not impair wound healing. It also does not have any significant effects on circulating blood cells or bone marrow leukocytes as a single agent or impair hematopoetic recovery after concomitant cytotoxic anti-cancer agent challenge. This novel compound has therapeutic potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.
2nd international workshop on software engineering methods in spreadsheets (SEMS 2015) (2015)

Spreadsheets are heavily used in industry, because they are easily written and adjusted, using an intuitive visual interface. They often start out as simple tools; however, over time spreadsheets can become increasingly complex, up to the point where they become complicated and inflexible. In many ways, are similar to software: both concern the storage and manipulation of data and the presentation of results to the user. Because of this similarity, many methods and techniques from software engineering can be applied to spreadsheets.The role of SEMS, the International Workshop on Software Engineering Methods in Spreadsheets is to explore the possibilities of applying successful methods from software engineering to spreadsheets. Some, like testing and visualization, have been tried before and can be built upon. For methods that have not yet been tried on spreadsheets, SEMS will serve as a platform for early feedback.The SEMS program included an industrial keynote, spreadsheet stories (success or failure), short and long research papers, a good mix of industrial and academic researchers, as well as lively discussion and debate.
CD4+CD25+ regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy (2005)

CD4+CD25+ regulatory T cells (Tregs) are essential negative regulators of immune responses. Here, we examined the signaling properties of human Tregs, using CD4+CD25+ Treg and CD4+CD25- control (Tcont) cell lines generated from cord blood. Treg cell lines were markedly hyporesponsive to stimulation with dendritic cells and with anti-CD3/CD28-coated beads. Hyporesponsiveness was reversed by exogenous interleukin-2 (IL-2). T-cell receptor (TCR)-CD3/CD28-mediated activation of Rap1 and Akt was retained in Tregs, but activation of Ras, mitogenactivated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated kinase 1/2 (Erk1/2) was impaired. Tregs were blocked from cell cycle progression due to decrease of cyclin E and cyclin A and increase of p27kip1 (p27kip cyclin dependent kinase inhibitor). IL-2 induced sustained increase of cyclin E and cyclin A and prevented up-regulation of p27kip1. Tregs had high susceptibility to apoptosis that was reversed by IL-2, which correlated with activation of Erk1/2, up-regulation of Bcl-x(L) (B-cell CLL/lymphoma 2-like nuclear gene encoding mitochondrial protein, transcript variant 2), and phosphorylation of Bad (Bcl2 antagonist of cell death) at Ser112. Thus, Tregs share biochemical characteristics of anergy, including abortive activation of Ras-MEK-Erk, increased activation of Rap1, and increased expression of p27kip1. In addition, our results indicate that TCR-CD3/CD28-mediated and IL-2 receptor-mediated signals converge at the level of MEK-Erk kinases to regulate Treg survival and expansion and suggest that manipulation of the MEK-Erk axis may represent a novel strategy for Treg expansion for immunotherapy.