gebhart/patrepeval huggingface dataset:
Variant cell lines selected for alterations in the function of the hyaluronan receptor CD44 show differences in glycosylation. (1995)

CD44 is a major cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA). However, the ability of CD44 to bind ligand is strictly regulated. Three activation states of CD44 have been demonstrated: (a) inactive; (b) inducible (by certain CD44-specific mAb); and (c) constitutively active. Starting with two parental cell lines expressing CD44 in the inactive state, a pre-B cell (RAW 253) and a fibroblast (L cells), we used fluorescence-activated cell sorting with fluorescein-conjugated hyaluronan in the presence of inducing mAb to derive variant cell lines with CD44 in the inducible state. Constitutively active derivatives were isolated from the inducible variants by a further round of fluorescence-activated cell sorting in the absence of inducing antibody. However, constitutively active variants could not be isolated directly from parental cells expressing CD44 in the inactive state. These results suggest that two genetic events must occur to obtain an active CD44-HA receptor from an inactive receptor. Variant and parental cell-derived CD44 molecules exhibited differences in migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis that were partly attributable to differences in N-linked glycosylation. Furthermore, culture in tunicamycin for 2-3 d converted parental and inducible cell lines into cells showing constitutive CD44-mediated HA binding. Also, removal of cell surface glycosaminoglycan chains by culture of cells in p-nitrophenyl beta-D-xylopyranoside or treatment with chondroitinase ABC resulted in conversion of cells with an inactive CD44 receptor to an inducible state. These results indicate that carbohydrate side chains of CD44 and/or other molecules on the cell surface that interact with CD44 are potentially involved in regulating the HA-binding function of CD44 on the cell surface.
Buck-boost DC-AC inverter: proposal for a new control strategy (2004)

The buck-boost DC-AC inverter is a special topology consisting of two buck-boost DC-DC converters that generate an AC output voltage in a single stage. This is achieved by means of driving both buck-boost DC-DC converters with two 180/spl deg/ phase-shifted DC-biased sinusoidal references. The differential output voltage is therefore an AC output voltage whose peak value is independent of the DC input voltage. The advantageous configuration of the buck-boost DC-AC inverter (AC voltage generated in a single stage, reduced number of semiconductors, small losses, output voltage naturally filtered, no dependence on the input voltage level, etc.) has a drawback related to the control of both buck-boost, as they are required to work in a variable operating point condition. This paper proposes a new double-loop control strategy for both buck-boost DC-DC converters that includes different compensations and feed-forward loops that make possible a fast and accurate control of both converters in a variable operating point condition. In addition, the proposed strategy achieves a high immunity to external perturbations such as input voltage and output load disturbances. Simulation tests show the robust performance in these situations as well as in case of transient short circuits and nonlinear loads connection.
Insulin Inhibits the Pro-Inflammatory Transcription Factor Early Growth Response Gene-1 (Egr)-1 Expression in Mononuclear Cells (MNC) and Reduces Plasma Tissue Factor (TF) and Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations (2002)

We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-kappa B (a pro-inflammatory transcription factor) content in MNC while also reducing the plasma concentration of NF-kappa B dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5% dextrose (100 mL/h) and KCI (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 +/- 14% of basal level) and 4 h (47 +/- 17% of the basal level; P<0.01). PAI-1 levels (basal = 100%) decreased significantly after insulin infusion at 2 h (57 +/- 6.7% of the basal level) and at 4 h (58 +/- 8.3% of the basal level; P<0.001). Plasma TF levels (basal = 100%) decreased to 76 +/- 7.7% of the basal level at 2 h and to 85 +/- 10.4% of the basal level at 4 h (P<0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.
PSOLAR: design, utility, and preliminary results of a prospective, international, disease-based registry of patients with psoriasis who are receiving, or are candidates for, conventional systemic treatments or biologic agents. (2012)

PSOLAR is a disease-based registry designed to assess therapeutic risk and benefit in the general psoriasis population.
Progress in the development of immunotherapy for the treatment of patients with cancer (2001)

Several recent developments have hallmarked progress in tumour immunology and immunotherapy. The use of interleukin-2 (IL-2) in cancer patients demonstrated that an immunological manipulation was capable of mediating the regression of established growing cancers in humans. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing patients against these antigens has opened important new avenues of exploration for the development of effective active and cell-transfer immunotherapies for patients with cancer.
Health Monitoring of Composite Material Structures Using a Vibrometry Technique (1998)

Large composite material structures such as aircraft and Reusable Launch Vehicles (RLVS) operate in severe environments comprised of vehicle dynamic loads, aerodynamic loads, engine vibration, foreign object impact, lightning strikes, corrosion, and moisture absorption. These structures are susceptible to damage such as delamination, fiber breaking/pullout, matrix cracking, and hygrothermal strain. To ensure human safety and load-bearing integrity, these structures must be inspected to detect and locate often invisible damage and faults before becoming catastrophic. Moreover, nearly all future structures will need some type of in-service inspection technique to increase their useful life and reduce maintenance and overall costs. Possible techniques for monitoring the health and indicating damage on composite structures include: c-scan, thermography, acoustic emissions using piezoceramic actuators or fiber-optic wires with gratings, laser ultrasound, shearography, holography, x-ray, and others. These techniques have limitations in detecting damage that is beneath the surface of the structure, far away from a sensor location, or during operation of the vehicle. The objective of this project is to develop a more global method for damage detection that is based on structural dynamics principles, and can inspect for damage when the structure is subjected to vibratory loads to expose faults that may not be evident by static inspection. A Transmittance Function Monitoring (TFM) method is being developed in this project for ground-based inspection and operational health monitoring of large composite structures as a RLV. A comparison of the features of existing health monitoring approaches and the proposed TFM method is given.
How I treat polycythemia vera (2012)

Polycythemia vera (PV) is a clonal disorder characterized by unwarranted production of red blood cells. In the majority of cases, PV is driven by oncogenic mutations that constitutively activate the JAK-STAT signal transduction pathway, such as JAK2 V617F, or exon 12 mutations or LNK mutations. Diagnosis of PV is based on the WHO criteria. Diagnosis of post-PV myelofibrosis is established according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria. Different clinical presentations of PV are discussed. Prognostication of PV is tailored to the most frequent complication during follow-up, namely, thrombosis. Age older than 60 years and prior history of thrombosis are the 2 main risk factors for disease stratification. Correlations are emerging between leukocytosis, JAK2(V617F) mutation, BM fibrosis, and different outcomes of PV, which need to be confirmed in prospective studies. In my practice, hydroxyurea is still the "gold standard" when cytoreduction is needed, even though pegylated IFN-alfa-2a and ruxolitinib might be useful in particular settings. Results of phase 1 or 2 studies concerning these latter agents should however be confirmed by the ongoing randomized phase 3 clinical trials. In this paper, I discuss the main problems encountered in daily clinical practice with PV patients regarding diagnosis, prognostication, and therapy.
IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients (2001)

IL-15 is a critical cytokine for the maintenance of memory-phenotype CD8 cells in mice. Here, we investigated the role of IL-15 in the neurological disease termed human T cell lymphotropic virus I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The high number of viral-specific CD8 cells in these patients is associated with inflammatory responses in the central nervous system. Because IL-15 is overexpressed in these patients, we asked whether IL-15 contributes to the persistence of human T cell lymphotropic virus I viral-specific CD8 cells. Using ex vivo cultures of HAM/TSP peripheral blood mononuclear cells, we demonstrated that in the majority of patients examined here blocking IL-15 action resulted in a decrease in the number of viral-specific CD8 cells. This decrease was caused by both inhibition of proliferation and induction of apoptosis in these cells. The data indicate that IL-15 plays a major role in the maintenance of viral-specific CD8 cells in HAM/TSP.
Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes (2005)

By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by more than 500 bp and thus are very likely to constitute mutually distinct alternative promoters. To our surprise, at least 7674 (52%) human RefSeq genes were subject to regulation by putative alternative promoters (PAPs). On average, there were 3.1 PAPs per gene, with the composition of one CpG-island-containing promoter per 2.6 CpG-less promoters. In 17% of the PAP-containing loci, tissue-specific use of the PAPs was observed. The richest tissue sources of the tissue-specific PAPs were testis and brain. It was also intriguing that the PAP-containing promoters were enriched in the genes encoding signal transduction-related proteins and were rarer in the genes encoding extracellular proteins, possibly reflecting the varied functional requirement for and the restricted expression of those categories of genes, respectively. The patterns of the first exons were highly diverse as well. On average, there were 7.7 different splicing types of first exons per locus partly produced by the PAPs, suggesting that a wide variety of transcripts can be achieved by this mechanism. Our findings suggest that use of alternate promoters and consequent alternative use of first exons should play a pivotal role in generating the complexity required for the highly elaborated molecular systems in humans.
Understanding data lifetime via whole system simulation (2004)

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Cellular Effects of Deep Brain Stimulation: Model-Based Analysis of Activation and Inhibition (2004)

Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders. However, fundamental questions remain about the effects of DBS on neurons surrounding the electrode. Experimental studies have produced apparently contradictory results showing suppression of activity in the stimulated nucleus, but increased inputs to projection nuclei. We hypothesized that cell body firing does not accurately reflect the efferent output of neurons stimulated with high-frequency extracellular pulses, and that this decoupling of somatic and axonal activity explains the paradoxical experimental results. We studied stimulation using the combination of a finite-element model of the clinical DBS electrode and a multicompartment cable model of a thalamocortical (TC) relay neuron. Both the electric potentials generated by the electrode and a distribution of excitatory and inhibitory trans-synaptic inputs induced by stimulation of presynaptic terminals were applied to the TC relay neuron. The response of the neuron to DBS was primarily dependent on the position and orientation of the axon with respect to the electrode and the stimulation parameters. Stimulation subthreshold for direct activation of TC relay neurons caused suppression of intrinsic firing (tonic or burst) activity during the stimulus train mediated by activation of presynaptic terminals. Suprathreshold stimulation caused suppression of intrinsic firing in the soma, but generated efferent output at the stimulus frequency in the axon. This independence of firing in the cell body and axon resolves the apparently contradictory experimental results on the effects of DBS. In turn, the results of this study support the hypothesis of stimulation-induced modulation of pathological network activity as a therapeutic mechanism of DBS.
Prognostic Effect of Epithelial and Stromal Lymphocyte Infiltration in Non–Small Cell Lung Cancer (2008)

High densities of CD4+ and CD8+ lymphocytes in the stroma are independent positive prognostic indicators for resected NSCLC patients. This may suggest that these cells are mediating a strong antitumor immune response in NSCLC.
Total synthesis of (S)-12-hydroxy-5,8,14-cis,-10-trans-eicosatetraenoic acid (Samuelsson's HETE) (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (S)-12-hydroxy-5,8,14-cis,-10-trans-eicosatetraenoic acid (Samuelsson's HETE)E. J. Corey, Haruki Niwa, and Jochen KnolleCite this: J. Am. Chem. Soc. 1978, 100, 6, 1942–1943Publication Date (Print):March 1, 1978Publication History Published online1 May 2002Published inissue 1 March 1978https://pubs.acs.org/doi/10.1021/ja00474a058https://doi.org/10.1021/ja00474a058research-articleACS PublicationsRequest reuse permissionsArticle Views2374Altmetric-Citations112LEARN 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
SMN regulates axonal local translation via miR-183/mTOR pathway (2014)

Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3' UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn-mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology.
First Evidence of a Water‐Soluble Plutonium(IV) Hexanuclear Cluster (2016)

The singular Pu IV hexanuclear cluster [Pu 6 (OH) 4 O 4 ] 12+ stabilized by 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) ligands was structurally characterized for the first time both in the solid state and in water solution by using X‐ray diffraction and X‐ray absorption and UV/Vis spectroscopy. The stability of this cluster in water and its high solubility over a large pH range are of upmost importance for plutonium environmental speciation with potential applications in a related migration model.
Photocontrol of DNA Duplex Formation by Using Azobenzene-Bearing Oligonucleotides (2001)

The duplex-forming activities of oligonucleotides can be photomodulated by incorporation of an azobenzene unit. Upon isomerizing the trans-azobenzene to the cis form by irradiation with UV light, the T(m) value of the duplex (with the complementary DNA) is lowered so that the duplex is dissociated. The duplex is formed again when the cis-azobenzene is converted to the trans-azobenzene by irradiation with visible light. The photoregulation is successful irrespective of the position of the azobenzene unit in the oligonucleotides. The trans-azobenzene in the oligonucleotides intercalates between two DNA base pairs in the duplexes and stabilizes them because of a favorable enthalpy change. The nonplanar structure of a cis-azobenzene is unfavorable for such an interaction. These photoresponsive oligonucleotides are promising candidates for the regulation of various bioreactions.
Interaction between the thyristor circuit and the unijunction trigger circuit (2003)

By analyzing the relation between the movement of internal mobile eletron and the outside condition while thyristor and unijunction working ,the mutual effect between the thyristor commutating circuit and unijunction trigger circuit is explained,the inside and outside reasons about the effect are analyzed ,and the methods to remove the unhealthy influence are introduced .
Inhibition of Lung Carcinogenesis and Effects on Angiogenesis and Apoptosis in A/J Mice by Oral Administration of Green Tea (2004)

Oral administration of tea (Camellia sinensis) has been shown to inhibit the formation and growth of several tumor types in animal models. The present study investigated the effects of treatment with different concentrations of green tea on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Two days after a single dose of NNK (100 mg/kg body weight, i.p.), the mice were given 0.1, 0.2, 0.4, and 0.6% green tea solution (1, 2, 4, and 6 g of tea solids, respectively, dissolved in 1 l of water), 0.02% caffeine, or water as the sole source of drinking fluid until the termination of the experiment. Only the treatment with 0.6% tea preparation significantly reduced lung tumor multiplicity (mean +/- SE, 6.07 +/- 0.77 vs. 8.60 +/- 0.50 tumors per mouse, P = 0.018). Treatment with 0.6% tea also inhibited angiogenesis, as indicated by the lower microvessel density (number of blood vessels/mm2) based on immunostaining for the von Willebrand factor antigen (81.9 +/- 9.5 vs. 129.4 +/- 8.2, P = 0.0018) and anti-CD31 antibody staining (465.3 +/- 61.4 vs. 657.1 +/- 43.6, P = 0.0012). Significantly lower vascular endothelial growth factor immunostaining scores were also observed in the 0.6% tea-treated group (0.98 +/- 0.17 vs. 1.43 +/- 0.07, P = 0.006). The apoptosis index was significantly higher in lung adenomas from 0.6% tea-treated mice based on morphological analysis of cell apoptosis (2.51 +/- 0.18% vs. 1.57 +/- 0.11%, P = 0.00005), and the result was further confirmed using the TUNEL method. Inhibition of angiogenesis and the induction of apoptosis by green tea may be closely related to the inhibition of pulmonary carcinogenesis.
The Human Genome Sequence and the Analysis of Multifactorial Traits (2007)

The human genome probably codes for about 10,000 basic functional units, most of which are functionally related families of genes occurring in one or more closely linked clusters. This relatively limited complexity means that a knowledge of the complete gene sequence is well within our grasp and will be fundamental to the analysis of complex multifactorial traits, including all the major chronic human diseases. Genetic marker segregation among 'affected' individuals in a pedigree, however complex, can now be done by using the essentially unlimited collection of restriction fragment length DNA polymorphisms. This can, in principle, identify all the inherited components of any complex trait and, with a knowledge of the human gene sequence, identify their functional basis. Thus one can now envisage a complete genetic and functional analysis of all complex inherited traits, including the major chronic diseases, and normal variation in physical and behavioural attributes.
Antagonism between Bacteriostatic and Bactericidal Antibiotics Is Prevalent (2014)

Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion of the use of combination therapy requires knowledge of how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal drugs are most potent with actively dividing cells, then the inhibition of growth induced by a bacteriostatic drug should result in an overall reduction of efficacy when the drug is used in combination with a bactericidal drug. Our goal here was to investigate this hypothesis systematically. We first constructed time-kill curves using five different antibiotics at clinically relevant concentrations, and we observed antagonism between bactericidal and bacteriostatic drugs. We extended our investigation by performing a screen of pairwise combinations of 21 different antibiotics at subinhibitory concentrations, and we found that strong antagonistic interactions were enriched significantly among combinations of bacteriostatic and bactericidal drugs. Finally, since our hypothesis relies on phenotypic effects produced by different drug classes, we recreated these experiments in a microfluidic device and performed time-lapse microscopy to directly observe and quantify the growth and division of individual cells with controlled antibiotic concentrations. While our single-cell observations supported the antagonism between bacteriostatic and bactericidal drugs, they revealed an unexpected variety of cellular responses to antagonistic drug combinations, suggesting that multiple mechanisms underlie the interactions.