gebhart/patrepeval huggingface dataset:
Life-Threatening Complications of Systemic Lupus Erythematosus (2011)

The major cause of death in longstanding lupus is accelerated atherosclerosis leading to cardiovascular disease. Early in lupus, the major causes of death are active lupus and infection. Life-threatening or organ-threatening lupus is not rare. Multiple organs including skin (necrosis), hematologic (thrombocytopenia, hemolytic anemia, neutropenia, catastrophic antiphospholipid syndrome, and thrombotic thrombocytopenic purpura), heart (pericardial tamponade, myocarditis), lung (alveolar hemorrhage, pulmonary hypertension), gastrointestinal (vasculitis, pancreatitis), adrenal insufficiency, and neurologic (myelitis) may be encountered.
Point of Care Diagnostics: Status and Future (2011)

The most commonly used test for monitoring heparin therapy is the activated partial thromboplastin time (aPTT). The response of available aPTT reagents to heparin varies significantly. The aim of this study was to highlight the differences between aPTT reagents stored in a dried format to select the most suitable formulations to be used for the development of point-of-care diagnostic devices used for monitoring of unfractionated heparin dose response. METHODS:\nTen reagents were analysed in terms of their performance in liquid and in dried form after storage for 24 h and 14 days. Performance was assessed by measurement of the clotting time (CT) as evidenced by the onset of thrombin formation using a chromogenic thrombin substrate in plasma samples activated with these formulations. RESULTS:\nReagents in all of the three forms tested (liquid, 24 h and 14 days) resulted in significant shortening of CTs in comparison with the nonactivated plasma CT. Liquids returned more rapid CTs in comparison with dried reagents. Most of the reagents were more sensitive to heparin in dried, rather than in liquid form. Dried reagents based on kaolin as a surface activator were notably more effective in achieving short CT than others, while dried reagents composed of silica and synthetic phospholipids were the most sensitive to heparin. CONCLUSION:\nTwo reagents, namely aPTT-SP and SynthASIL both of which are based on synthetic phospholipids and silica, were identified as promising candidates for incorporation into point-of-care diagnostic device platforms as dried reagents.
Enhanced Cancer Growth in Mice Administered Daily Human-Equivalent Doses of Some H1-Antihistamines: Predictive In Vitro Correlates (1994)

These in vitro tests may prove valuable to screen potential tumor growth promoters.
Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase, RNase H, and Integrase Activities by Hydroxytropolones (2005)

Human immunodeficiency virus type I reverse transcriptase (RT) possesses distinct DNA polymerase and RNase H sites, whereas integrase (IN) uses the same active site to perform 3'-end processing and strand transfer of the proviral DNA. These four enzymatic activities are essential for viral replication and require metal ions. Two Mg2+ ions are present in the RT polymerase site, and one or two Mg2+ ions are required for the catalytic activities of RNase H and IN. We tested the possibility of inhibition of the RT polymerase and RNase H as well as the IN 3'-end processing and transfer activities of purified enzymes by a series of 3,7-dihydroxytropolones designed to target two Mg2+ ions separated by approximately 3.7 angstroms. The RT polymerase and IN 3' processing and strand transfer activities were inhibited at submicromolar concentrations, while the RNase H activity was inhibited in the low micromolar range. In all cases, the lack of inhibition by tropolones and O-methylated 3,7-dihydroxytropolones was consistent with the active molecules binding the metal ions in the active site. In addition, inhibition of the DNA polymerase activity was shown to depend on the Mg2+ concentration. Furthermore, selective inhibitors were identified for several of the activities tested, leaving some potential for design of improved inhibitors. However, all tested compounds exhibited cellular toxicity that presently limits their applications.
Ideality in a Fiber-Taper-Coupled Microresonator System for Application to Cavity Quantum Electrodynamics (2003)

The ability to achieve near lossless coupling between a waveguide and a resonator is fundamental to many quantum-optical studies as well as to practical applications of such structures. The nature of loss at the junction is described by a figure of merit called ideality. It is shown here that under appropriate conditions ideality in excess of 99.97% is possible using fiber-taper coupling to high-Q silica microspheres. To verify this level of coupling, a technique is introduced that can both measure ideality over a range of coupling strengths and provide a practical diagnostic of parasitic coupling within the fiber-taper-waveguide junction.
Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current (1996)

Heteromultimer formation between Kv potassium channel subfamilies with the production of a novel current is reported for the first time. Protein-protein interactions between Kv2.1 and electrically silent Kv6.1 alpha-subunits were detected using two microelectrode voltage clamp and yeast two-hybrid measurements. Amino terminal portions of Kv6.1 were unable to form homomultimers but interacted specifically with amino termini of Kv2.1. Xenopus oocytes co-injected with Kv6.1 and Kv2.1 cRNAs exhibited a novel current with decreased rates of deactivation, decreased sensitivity to TEA block, and a hyperpolarizing shift of the half maximal activation potential when compared to Kv2.1. Our results indicate that Kv channel subfamilies can form heteromultimeric channels and, for the first time, suggest a possible functional role for the Kv6 subfamily.
On the Drive Systems for High-Performance Machines (1984)

The choice of actuators and transmissions in high performance machines and manipulators can have a profound effect on the time required for a specified machine task. For systems operating with mechanical constraints, such as limits on allowable angular velocities in motors, designing for greatest achievable acceleration will not always minimize move time. In this paper the effects on performance of ranges of choices of actuators and transmission mechanisms are evaluated, and guidelines for choosing the optimal drive elements are presented.
Hybrid Method for Metallization of Glass Interposers (2013)

Glass has gained interest as a material for interposer technology due to its low/adjustable thermal expansion coefficient, low cost, good dimensional stability and availability in large panels compared to silicon substrates. However, the metallization of glass constitutes a major challenge owing to the notoriously poor adhesion between glass and metals. In this work, strategies for improving the adhesion to the glass surface and for providing at the same time continuous coating of through glass holes (TGHs) are explored. As result, a hybrid approach for glass metallization based on sputtering of a thin Ti-Cu layer and subsequent coating by electroless Ni deposition is introduced and developed. The proposed approach takes advantage of the good adhesion of very thin sputtered films on glass surfaces and combines this with the ability of electroless plating to bridge center regions of high aspect TGHs that are inaccessible to metallization by sputtering. Robust layers deposited by the hybrid method, shown to continuously coat the surface and TGHs, allow for further Cu elctrodeposition on the way to final circuitry. Approaches explored for seeding, coating and further metallization are described in detail. Results of cross-section analysis, optical microscopy, and SEM are also presented.
P- and T-Wave Delineation in ECG Signals Using a Bayesian Approach and a Partially Collapsed Gibbs Sampler (2010)

Detection and delineation of P- and T-waves are important issues in the analysis and interpretation of electrocardiogram (ECG) signals. This paper addresses this problem by using Bayesian inference to represent a priori relationships among ECG wave components. Based on the recently introduced partially collapsed Gibbs sampler principle, the wave delineation and estimation are conducted simultaneously by using a Bayesian algorithm combined with a Markov chain Monte Carlo method. This method exploits the strong local dependency of ECG signals. The proposed strategy is evaluated on the annotated QT database and compared to other classical algorithms. An important feature of this paper is that it allows not only for the detection of P- and T-wave peaks and boundaries, but also for the accurate estimation of waveforms for each analysis window. This can be useful for some ECG analysis that require wave morphology information.
MET Activation Mediates Resistance to Lapatinib Inhibition of HER2 -Amplified Gastric Cancer Cells (2012)

HER2 amplification is found in more than 15% of gastric cancers and is associated with poor clinical outcome. Lapatinib, a dual HER2 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown promising in vitro results in treating HER2(+) cancer cells. However, several studies have shown that activation of alternative receptor tyrosine kinases can mediate resistance to HER-targeted therapy. Here, we investigated whether activated MET can confer resistance to lapatinib inhibition of gastric cancer cells. A panel of gastric cancer cell lines was treated with lapatinib, and we observed that cell proliferation was reduced by 70% and that the degree of HER2 amplification corresponds to sensitivity to lapatinib. Immunoblotting analysis indicated that phosphorylation of HER2, EGFR, MET, AKT, and extracellular signal-regulated kinase was inhibited by lapatinib and presumably led to cell-cycle arrest as observed with flow cytometry. Hepatocyte growth factor (HGF) activation of MET receptors rescued cells from lapatinib-induced growth inhibition by restimulating the downstream pathways and restoring normal cell-cycle progression. This rescue effect could be abrogated by inhibiting MET with PHA-665752 (a highly specific MET inhibitor) or downregulating MET expression with short interfering RNA. No synergy in growth inhibition was observed when cells were treated with a combination of lapatinib and PHA-665752. Repeat studies using insulin-like growth factor 1 and fibroblast growth factor 3 could not uniformly rescue the lapatinib-treated gastric cancer cells. In conclusion, HGF/MET-mediated resistance to lapatinib is a novel mechanism of resistance to HER2-targeted agents in gastric cancer cells. Development of inhibitors targeting multiple receptors or common downstream signaling proteins merits further investigation.
Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method (1998)

High enantioselectivity can be achieved when chiral oxazaborolidines are used as catalysts in the reduction of ketones by borane. In the transition state on the way to the complex chiral compounds, the two reactants are activated and held in close proximity by the catalyst, as shown below.
A Pilgrim's Progression in Representation: John Bunyan's Use of Image, Word, and Imagination (2003)

The Pilgrim's Progress is more than a timeless allegory that encodes 1 Protestant doctrine.It also reveals strong undercurrents of the theological controversies in John Bunyan's time-specifically the longwarring debate over image, word, and imagination.Ernest B. Gilman observes, "What echoes in the poetic record of the age [of the English Reformation] is ... the continuous interplay, and the occasional major collision, between strongly iconic and strongly iconoclastic impulses" (3).The English Protestant iconoclasm that tore down pictures in churches and replaced them with words of scripture entered the literature of the time.Bunyan had served in the English Civil War on Cromwell's side; he would have been well versed in issues of iconoclasm.' .A5 a writer, he knew the power of representation in word and image.The Puritans' iconoclastic efforts were spurred by a desire to uproot anything popish, anything approaching Catholicism's iconic traditions.They condemned Catholic means of representation-visual images-as idolatrous.Calvinist Protestants decried visual images as a faulty means of representation of the truth; they saw words as a more trustworthy means of representation."Protestantism," Thomas Luxon observes, "is a radically word-centered religion" (444).And even in this logo-centric approach, not all Protestants considered all realms of language trustworthy means of representing truth.Some Puritans saw allegory as inappropriate because it involved the imagination so heavily, akin to Catholic 'Lasting much of the 1640s, the English Civil War was basically a war between the supporters of King Charles I and those of Puritan Oliver C romwell.Because of Laud's work under Charles, much of the high church ceremony and visual ornamentation returned.Puritans wanted to keep these iconic tendencies in check, stemming from their belief that the visual could mislead.The Puritan iconoclasm would reign under Cromwell's Protectorate.' Ernest B. Gilman writes chat "the Anglican establishment attempted to negotiate ... under Laud, that since popery had been abolished and the people were now properly admonished on the abuse images, there could be no danger of idolatry in Laud's program" (40).' In "Representation," Mitchell describes three modes of representation: iconic (representation through resemblance), symbolic (representation through arbitrary assignment), and indexical (representation through cause and effect or existential evidence) (I 4).
Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging (2006)

Despite functional evidence for disulfide bond-reducing activity in endosomal compartments, the mechanistic details pertaining to such process (e.g., kinetics and sites of disulfide reduction) remain largely controversial. To address these questions directly, we have synthesized a previously uncharacterized fluorescent folate conjugate, folate-(BODIPY FL)-SS-rhodamine (folate-FRET), that changes fluorescence from red to green upon disulfide bond reduction. Using this construct, we have observed that disulfide reduction: (i) occurs with a half-time of 6 h after folate-FRET endocytosis, (ii) begins in endosomes and does not depend significantly on redox machinery located on the cell surface or within the lysosome or the Golgi apparatus, (iii) occurs independently of endocytic vesicle trafficking along microtubules, and (iv) yields products that are subsequently sorted into distinct endosomes and trafficked in different directions. Finally, colocalization of folate and transferrin receptors suggest that conclusions derived from this study may apply to other endocytic pathways.
Replication of hepatitis delta virus RNA in mice after intramuscular injection of plasmid DNA (1995)

To establish a readily manipulable small-animal system for the study of human hepatitis delta virus (HDV) replication in vivo, plasmid DNAs containing head-to-tail cDNA dimers of HDV were inoculated intramuscularly into mice. Genomic-sense HDV RNA was detected in the injected muscle within 1 week and increased to substantial levels by week 7 postinjection. The intramuscular accumulation of HDV RNA was determined to be the direct result of viral RNA replication by three lines of evidence: (i) injected tissues also accumulated antigenomic-sense HDV RNA, (ii) plasmid DNA that synthesized primary transcripts of antigenomic sense also led to the accumulation of genomic-sense HDV RNA, and (iii) injection of a cDNA dimer defective in antigenomic RNA cleavage failed to produce detectable HDV RNA in muscle. Immunohistochemical analysis of injected muscle demonstrated the presence and nuclear localization of hepatitis delta antigen in myocytes. Finally, sera from DNA-injected mice contained antibodies specific for delta antigen, indicating the induction of an immunological response to the intracellularly expressed antigen. These findings demonstrated the ability of HDV RNA to replicate in skeletal muscle and provide a useful system for the study of HDV replication, delta antigen processing, and its presentation to the immune system in vivo. Furthermore, this system offers an efficiently replicating RNA as a potential vehicle for in vivo gene transfer.
Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells (1990)

We investigated the mechanisms by which cytokines lead to a diminished responsiveness of vascular smooth muscle to vasoconstrictors. The attenuation of noradrenaline-induced contraction by 6 to 24 h incubations with the cytokines, tumor necrosis factor and interleukin-1, in endothelium-denuded rabbit aorta was associated with an increase in intracellular cyclic GMP level. This increase was abolished by the stereoselective inhibitor of nitric oxide-synthase, NG-nitro-L-arginine and by cycloheximide. Formation of nitric oxide was detected in the cytosol of cytokine-treated native and cultured smooth muscle cells by activation of purified soluble guanylate cyclase, and depended on tetrahydrobiopterin, but not on Ca2(+)-calmodulin. The results indicate that cytokines induce a nitric oxide-synthase of the macrophage-type in vascular smooth muscle.
Antiphospholipid Antibodies Attenuate Endothelial Repair and Promote Neointima Formation in Mice (2014)

APLs blunt endothelial repair, and there is related aPL-induced exaggeration in neointima formation after endothelial injury in mice. The initiating process entails NO deficiency mediated by β2-glycoprotein I recognition by aPLs and apolipoprotein E receptor 2. The modulation of endothelial apolipoprotein E receptor 2 function or NO bioavailability may represent new interventions to prevent the nonthrombotic vascular occlusion and resulting cardiovascular disorders that afflict antiphospholipid syndrome patients.
Anti-B cell therapy (Rituximab) in the treatment of autoimmune diseases (2005)

The use of B cell depletion as a mode of treatment for non-Hodgkin's lymphoma was first utilized in 1997 when Rituximab, a chimeric human-mouse monoclonal antibody which has a high affinity to the CD20 antigen expressed on B cells, became available. Over 500000 lymphoma patients have been treated worldwide with this drug and it has a good safety record. The notion that B cells might be critical to the development of rheumatoid arthritis led to the extension of the use of B cell depletion to this condition and a recent double blind controlled trial has shown very encouraging results. In addition, B cell depletion either using Rituximab alone, or in combination with cyclophosphamide and corticosteroids has also been reported to have been of great benefit in some patients with severe systemic lupus erythematosus albeit in open label studies. This review considers the mechanism of action of the drug, the clinical trials that have been reported, and tries to place its current use in patients with autoimmune rheumatic disease in context.
Alveolar macrophages release an insulin-like growth factor I-type molecule. (1988)

Human alveolar macrophages, when activated, release a progression-type growth factor for fibroblasts that signals "competent" fibroblasts to replicate. The present study demonstrates that this growth activity is an insulin-like growth factor I (IGF-I)-type molecule. Partial purification of medium conditioned by activated alveolar macrophages using ion exchange and gel filtration chromatography revealed an IGF-I molecule as detected by an anti-IGF-I polyclonal antibody and that the specific activity of the progression-type growth activity tracked with the amount of IGF-I present. In a serum-free complementation test, the increase in fibroblast proliferation by alveolar macrophage IGF-I was reduced in a dose-response manner with an anti-IGF-I monoclonal antibody. The alveolar macrophage IGF-I displaced 125I-IGF-I from its receptor in a binding assay utilizing human lung fibroblasts and it stimulated type I IGF receptors purified from human lung fibroblasts to phosphorylate a tyrosine-containing artificial substrate. In contrast to the 7.6-kD serum IGF-I, gel chromatography revealed that the alveolar macrophage IGF-I had an apparent molecular mass of 26 kD, similar to other tissue IGF-Is. Alveolar macrophages expressed IGF-I mRNA transcripts as detected by solution hybridization using a 32P-labeled riboprobe complementary to exons I-II-III of the IGF-I gene. In the context of the known functions of the family of IGF-I molecules in cell growth, IGF-I released by activated alveolar macrophages may play a role in acute and chronic inflammatory disorders.
Community detection and graph partitioning (2013)

Many methods have been proposed for community detection in networks. Some of the most promising are methods based on statistical inference, which rest on solid mathematical foundations and return excellent results in practice. In this paper we show that two of the most widely used inference methods can be mapped directly onto versions of the standard minimum-cut graph partitioning problem, which allows us to apply any of the many well-understood partitioning algorithms to the solution of community detection problems. We illustrate the approach by adapting the Laplacian spectral partitioning method to perform community inference, testing the resulting algorithm on a range of examples, including computer-generated and real-world networks. Both the quality of the results and the running time rival the best previous methods.
Iron Metabolism and Iron Chelation in Sickle Cell Disease (2009)

This review highlights recent advances in iron metabolism that are relevant to sickle cell disease (SCD). SCD is a common hemoglobinopathy that results in chronic inflammation. Improved understanding of how iron metabolism is controlled by proteins such as hepcidin, ferroportin, hypoxia-inducible factor 1, and growth differentiation factor 15 have revealed how they are involved in the organ toxicity of SCD. SCD patients have lower levels of non-transferrin-bound iron (NTBI) relative to other hemoglobinopathies, such as thalassemia. Care for SCD now commonly uses transfusion that results in iron overload and necessitates the need for chelation. New oral chelation therapy using deferasirox (Exjade/ICL670) appears to be safe and may even lower the amount of toxic free NTBI and enhance patient compliance. Finally, we suggest that iron metabolism and trafficking is different in SCD compared to other hemoglobinopathies. The high levels of inflammatory cytokines in SCD may enhance macrophage/reticuloendothelial cell iron and/or renal cell iron retention. This makes the tissues that retain iron different in SCD, and thus the organs that fail in SCD are different from those of other hemoglobinopathies, such as the cardiomyopathy or endocrinopathies of thalassemia.